Nonlinear dynamics in infant respiration

0 downloads 0 Views 7MB Size Report
to solve these equations and obtain a solution (closed form, series, or numeric). One ... chaotic or definitely not and do so in about equal proportions. .... 6. Chapter 1. Exordium. The lungs are surrounded by three muscle groups: the ...... In practice one could guess a suitable value for de by successively embedding in higher.
Nonlinear dynamics in infant respiration Michael Small BSc (Hons)

UWA

This thesis is presented for the degree of Doctor of Philosophy of The University of Western Australia Department of Mathematics. 1998

ii

iii

To Sylvia.

iv

v Abstract Using inductance plethysmography it is possible to obtain a non-invasive measurement of the chest and abdominal cross-sectional area. These measurements are \representative" of the instantaneous lung volume. This thesis describes an analysis of the breathing patterns of human infants during quiet sleep using techniques of nonlinear dynamical systems theory. The purpose of this study is to determine if these techniques may be used to extend our understanding of the human respiratory system and its development during the rst few months of life. Ultimately, we wish to use these techniques to detect and diagnose abnormalities and illness (such as apnea and sudden infant death syndrome) from recordings of respiratory e ort during natural sleep. Previous applications of dynamical systems theory to biological systems have been primarily concerned with the estimation of dynamic invariants: correlation dimension, Lyapunov exponents, entropy and algorithmic complexity. However, estimating these numbers is has not proven useful in general. The study described in this thesis focuses on building models from time-series recordings and using these models to deduce properties of the underlying dynamical system. We apply a correlation dimension estimation algorithm in conjunction with well known surrogate data techniques and conclude that the respiratory system is not linear. To elucidate the nature of the nonlinearity within this complex system we apply a new type of radial basis modelling algorithm (cylindrical basis modelling) and generate new nonlinear surrogate data. New nonlinear radial (cylindrical) basis modelling techniques have been developed by the author to accurately model this data. This thesis presents new results concerning the use of correlation integral based statistics for surrogate data hypothesis testing. This extends the scope of surrogate data techniques to include hypotheses concerned with broad classes of nonlinear systems. We conclude that the human respiratory system behaves as a periodic oscillator with two or three degrees of freedom. This system is shown to exhibit cyclic amplitude modulation (CAM) during quiet sleep. By examining the eigenvalues of xed points exhibited by our models, and the qualitative features of the asymptotic behaviour of these models we nd further evidence to support this hypothesis. An analysis of Poincare sections and the stability of the periodic orbits of these models demonstrates that CAM is present in models of almost all data sets. Models which do not exhibit CAM often exhibit chaotic rst return maps. Some models are shown to exhibit period doubling bifurcations in the rst return map. To quantify the period and strength of CAM we suggest a new statistic based on an information theoretic reduction of linear models. The models we utilise o er substantial simpli cation of autoregressive models and provide superior results. We show that the period of CAM present before a sigh and the period of subsequent periodic breathing are the same. This suggests that CAM is ubiquitous but only evident during periodic breathing. Physiologically, CAM may be linked to an autoresucitation mechanism. We

vi observe a signi cantly increased incidence of CAM in infants at risk of sudden infant death syndrome and a higher incidence of CAM during apneaic episodes of bronchopulmonary dysplasic infants.

vii

Contents iii Abstract

v

List of Tables

xi

List of Figures

xiii

List of Publications

xv

Acknowledgements

xvii

I Introduction

1

1 Exordium

3

1.1 Dynamics of respiration . . . . . . . . . . . 1.1.1 Physiology . . . . . . . . . . . . . . 1.1.2 Pathology . . . . . . . . . . . . . . . 1.1.3 Chaos and physiology . . . . . . . . 1.1.4 Mathematical models of respiration . 1.1.5 Periodic respiration . . . . . . . . . 1.1.6 Motivation . . . . . . . . . . . . . . 1.2 Data collection . . . . . . . . . . . . . . . . 1.2.1 Experimental methodology . . . . . 1.2.2 Data . . . . . . . . . . . . . . . . . . 1.3 Thesis outline . . . . . . . . . . . . . . . . .

. . . . . . . . . . .

. . . . . . . . . . .

. . . . . . . . . . .

. . . . . . . . . . .

. . . . . . . . . . .

. . . . . . . . . . .

. . . . . . . . . . .

. . . . . . . . . . .

. . . . . . . . . . .

. . . . . . . . . . .

. . . . . . . . . . .

. . . . . . . . . . .

. . . . . . . . . . .

. . . . . . . . . . .

. . . . . . . . . . .

. . . . . . . . . . .

5 5 7 8 10 12 13 14 14 16 16

II Techniques from dynamical systems theory

19

2 Attractor reconstruction from time series

21

2.1 Reconstruction . . . . . . . . . . . . . . . . . 2.1.1 Embedding dimension de . . . . . . . 2.1.2 Embedding lag  . . . . . . . . . . . . 2.2 Correlation dimension . . . . . . . . . . . . . 2.2.1 Generalised dimension . . . . . . . . . 2.2.2 The Grassberger-Procaccia algorithm 2.2.3 Judd's algorithm . . . . . . . . . . . . 2.3 Radial basis modelling . . . . . . . . . . . . . 2.3.1 Radial basis functions . . . . . . . . .

. . . . . . . . .

. . . . . . . . .

. . . . . . . . .

. . . . . . . . .

. . . . . . . . .

. . . . . . . . .

. . . . . . . . .

. . . . . . . . .

. . . . . . . . .

. . . . . . . . .

. . . . . . . . .

. . . . . . . . .

. . . . . . . . .

. . . . . . . . .

. . . . . . . . .

21 22 23 24 25 26 27 29 29

viii 2.3.2 Minimum description length principle . . . . . . . . . . . . . . . 2.3.3 Pseudo linear models . . . . . . . . . . . . . . . . . . . . . . . . .

30 33

3 The method of surrogate data

37

III Analysis of infant respiration

43

4 Surrogate analysis

45

5 Embedding | Optimal values for respiratory data

65

3.1 The rationale and language of surrogate data . . . . . . . . . . . . . . . 3.2 Linear surrogates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3 Cycle shued surrogates . . . . . . . . . . . . . . . . . . . . . . . . . . .

4.1 On surrogate analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1.1 Test statistics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1.2 AAFT surrogates revisited . . . . . . . . . . . . . . . . . . . . . 4.1.3 Generalised nonlinear null hypotheses . . . . . . . . . . . . . . . 4.1.4 The \pivotalness" of dynamic measures . . . . . . . . . . . . . . 4.2 Correlation dimension as a pivotal test statistic | linear hypotheses . . 4.2.1 Linear hypotheses . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2.2 Calculations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2.3 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.3 Correlation dimension as a pivotal test statistic | nonlinear hypothesis 4.3.1 Nonlinear hypotheses . . . . . . . . . . . . . . . . . . . . . . . . 4.3.2 Calculations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.3.3 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.4 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.1 Embedding strategies . . . . . . . . . 5.2 Calculation of de . . . . . . . . . . . 5.3 Calculation of  . . . . . . . . . . . . 5.3.1 Representative values of  . . 5.3.2 Two dimensional embeddings

6 Nonlinear modelling

6.1 Modelling respiration . . . . . . 6.1.1 Data . . . . . . . . . . . 6.1.2 Modelling . . . . . . . . 6.2 Improvements . . . . . . . . . . 6.2.1 Basis functions . . . . . 6.2.2 Directed basis selection 6.2.3 Description length . . .

. . . . . . .

. . . . . . .

. . . . . . .

. . . . .

. . . . . . .

. . . . .

. . . . . . .

. . . . .

. . . . . . .

. . . . .

. . . . . . .

. . . . .

. . . . . . .

. . . . .

. . . . . . .

. . . . .

. . . . . . .

. . . . .

. . . . . . .

. . . . . . . . . . . .

. . . . . . . . . . . .

. . . . . . . . . . . .

. . . . . . . . . . . .

. . . . . . . . . . . .

. . . . . . . . . . . .

. . . . . . . . . . . .

. . . . . . . . . . . .

. . . . . . . . . . . .

. . . . . . . . . . . .

. . . . . . . . . . . .

. . . . . . . . . . . .

37 39 40

45 46 47 48 49 50 52 53 58 59 60 61 63 63 65 66 67 67 67

75

76 76 78 79 80 81 82

ix

6.3

6.4 6.5

6.6

6.2.4 Maximum likelihood . . . . . . . . . . . . . . . . 6.2.5 Linear modelling selection of embedding strategy 6.2.6 Simplifying embedding strategies . . . . . . . . . Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.3.1 Improved modelling . . . . . . . . . . . . . . . . 6.3.2 E ect of individual alterations . . . . . . . . . . 6.3.3 Modelling results . . . . . . . . . . . . . . . . . . Problematic data . . . . . . . . . . . . . . . . . . . . . . 6.4.1 Non-Gaussian noise . . . . . . . . . . . . . . . . 6.4.2 Non-identically distributed noise . . . . . . . . . Genetic algorithms . . . . . . . . . . . . . . . . . . . . . 6.5.1 Review . . . . . . . . . . . . . . . . . . . . . . . 6.5.2 Model optimisation . . . . . . . . . . . . . . . . . 6.5.3 Results . . . . . . . . . . . . . . . . . . . . . . . Conclusion . . . . . . . . . . . . . . . . . . . . . . . . .

7 Visualisation, xed points, and bifurcations 7.1 Visualisation . . . . 7.2 Phase space . . . . . 7.2.1 Results . . . 7.3 Flow . . . . . . . . . 7.4 Bifurcation diagrams 7.5 Conclusion . . . . .

. . . . . .

. . . . . .

. . . . . .

. . . . . .

. . . . . .

. . . . . .

8 Correlation dimension estimates

. . . . . .

8.1 Methods . . . . . . . . . . . . . . 8.1.1 Subjects . . . . . . . . . . 8.1.2 Data collection . . . . . . 8.2 Data analysis . . . . . . . . . . . 8.2.1 Dimension estimation . . 8.2.2 Linear surrogates . . . . . 8.2.3 Cycle shued surrogates . 8.2.4 Nonlinear surrogates . . . 8.3 Results . . . . . . . . . . . . . . . 8.3.1 Dimension estimation . . 8.3.2 Linear surrogates . . . . . 8.3.3 Cycle shued surrogates . 8.3.4 Nonlinear surrogates . . . 8.4 Discussion . . . . . . . . . . . . .

. . . . . .

. . . . . . . . . . . . . .

. . . . . .

. . . . . . . . . . . . . .

. . . . . .

. . . . . . . . . . . . . .

. . . . . .

. . . . . . . . . . . . . .

. . . . . .

. . . . . . . . . . . . . .

. . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

84 84 85 85 85 89 90 93 94 94 94 94 96 97 100

103

103 107 108 110 115 116

119

120 120 120 121 121 121 122 122 124 124 128 128 132 134

x 9 Reduced autoregressive modelling

9.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.2 Tidal volume . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.2.1 Subjects . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.2.2 Pre-processing . . . . . . . . . . . . . . . . . . . . . . . 9.3 Autoregressive modelling . . . . . . . . . . . . . . . . . . . . . . 9.3.1 Estimation of (a; b) . . . . . . . . . . . . . . . . . . . . . 9.4 Reduced autoregressive modelling . . . . . . . . . . . . . . . . . 9.4.1 Autoregressive models . . . . . . . . . . . . . . . . . . . 9.4.2 Description length . . . . . . . . . . . . . . . . . . . . . 9.4.3 Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.4.4 Data processing . . . . . . . . . . . . . . . . . . . . . . . 9.5 Experimental results . . . . . . . . . . . . . . . . . . . . . . . . 9.5.1 CAM detected using RARM . . . . . . . . . . . . . . . 9.5.2 RAR modelling results . . . . . . . . . . . . . . . . . . . 9.5.3 Veri cation of RARM algorithm with surrogate analysis 9.5.4 Prevalence of CAM and apnea . . . . . . . . . . . . . . 9.5.5 Pre-apnea periodicities . . . . . . . . . . . . . . . . . . . 9.6 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

137

137 139 139 139 141 143 143 145 146 147 148 149 149 150 151 151 154 157

10 Quasi-periodic dynamics

161

IV Conclusion

171

11 Conclusion

173

V Appendices

179

A Results of linear surrogate calculations

181

B Floquet theory calculations

187

Bibliography

191

10.1 Floquet theory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161 10.2 Poincare sections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 164 10.3 Remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 168

11.1 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173 11.2 Extensions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 176

xi

List of Tables 5.1 Calculation of  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68 6.1 Algorithmic performance . . . . . . . . . . . . . . . . . . . . . . . . . . . 88 6.2 Periodic behaviour . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93 6.3 GA performance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99 9.1 9.2 9.3 9.4

Detection of CAM using RARM . . . . . . . . . Results of the calculations to detect periodicities Prevalence of CAM and apnea . . . . . . . . . . CAM after sigh and RARM . . . . . . . . . . . .

. . . .

. . . .

. . . .

. . . .

. . . .

. . . .

. . . .

. . . .

. . . .

. . . .

. . . .

. . . .

. . . .

150 152 154 156

A.1 Hypothesis testing with standard surrogate tests . . . . . . . . . . . . . 186 B.1 Calculation of the stability of the periodic orbits of models . . . . . . . 189

xii

xiii

List of Figures 1.1 Publications of dynamical systems theory in medical literature . . . . . 1.2 Periodic breathing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

4 8

2.1 A time lag embedding . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 2.2 Correlation dimension from the distribution of inter-point distances . . . 28 2.3 Description length as a function of model size . . . . . . . . . . . . . . . 31 3.1 Generation of cycle shued surrogates . . . . . . . . . . . . . . . . . . . 40 4.1 Probability distribution for correlation dimension estimates of AR(2) processes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2 Probability density for correlation dimension estimates of a monotonic nonlinear transformation of AR(2) processes . . . . . . . . . . . . . . . . 4.3 Experimental data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.4 Probability density for correlation dimension estimates for surrogates of experimental data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.5 Experimental data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.6 Probability density for correlation dimension estimates for nonlinear surrogates of experimental data . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . .

54 55 56 57 61 62

5.1 5.2 5.3 5.4

False nearest neighbours . . . . . . . . . . . . . E ect of  on the shape of an embedding . . . Parameter r . . . . . . . . . . . . . . . . . . . . Dependence of shape of embedding on  and r

. . . .

. . . .

. . . .

. . . .

. . . .

. . . .

. . . .

. . . .

. . . .

. . . .

. . . .

. . . .

66 69 70 71

6.1 6.2 6.3 6.4 6.5 6.6 6.7 6.8 6.9

Data . . . . . . . . . . . . . . . . . . . . . . . . . . . Periodic breathing . . . . . . . . . . . . . . . . . . . Initial modelling results . . . . . . . . . . . . . . . . Improved modelling results . . . . . . . . . . . . . . Cylindrical basis model . . . . . . . . . . . . . . . . Short term behaviour . . . . . . . . . . . . . . . . . Periodic breathing . . . . . . . . . . . . . . . . . . . Surrogate calculations . . . . . . . . . . . . . . . . . E ect of parameter values on the genetic algorithm .

. . . . . . . . .

. . . . . . . . .

. . . . . . . . .

. . . . . . . . .

. . . . . . . . .

. . . . . . . . .

. . . . . . . . .

. . . . . . . . .

. . . . . . . . .

. . . . . . . . .

. . . . . . . . .

76 77 79 85 86 87 90 92 98

7.1 7.2 7.3 7.4 7.5

Small basis functions . . . . . . . . . . . . . . . . . . . . . . . . . . . Big basis functions . . . . . . . . . . . . . . . . . . . . . . . . . . . . The function f (y; y; : : : ; y ) for three models of a respiratory data set A sample model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Periodic model ow . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . .

. . . . .

104 105 107 109 111

xiv 7.6 Chaotic model ow . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112 7.7 Model ow . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113 7.8 The bifurcation diagram . . . . . . . . . . . . . . . . . . . . . . . . . . . 114 8.1 8.2 8.3 8.4 8.5 8.6 8.7 8.8

Cycle shued surrogates . . . . . . . . . . . . . . . . Correlation dimension estimates . . . . . . . . . . . . Dimension estimate for subject 8 . . . . . . . . . . . Dimension estimate for subject 2 . . . . . . . . . . . Linear surrogate calculations . . . . . . . . . . . . . Surrogate data . . . . . . . . . . . . . . . . . . . . . Dimension estimates for cycle randomised surrogates Nonlinear surrogate dimension estimates . . . . . . .

. . . . . . . .

. . . . . . . .

. . . . . . . .

. . . . . . . .

. . . . . . . .

123 125 126 127 129 130 131 133

9.1 Derivation of the tidal volume time series . . . . . . . . . . . . . . . . . 9.2 Stability diagram for equation (9.1) . . . . . . . . . . . . . . . . . . . . . 9.3 Surrogate data comparison of the estimates of (a2 + 4b) and a2 from data to algorithm 0 surrogates . . . . . . . . . . . . . . . . . . . . . . . . . . 9.4 Reduced autoregressive modelling algorithm . . . . . . . . . . . . . . . . 9.5 The surrogate data calculation for one data set . . . . . . . . . . . . . . 9.6 Pre-apnea periodicities . . . . . . . . . . . . . . . . . . . . . . . . . . . .

140 142 144 148 153 155

10.1 10.2 10.3 10.4

163 165 166 167

Free run prediction from a model with uniform embedding . Iterates of the Poincare section . . . . . . . . . . . . . . . . First return map for a large neighbourhood . . . . . . . . . First return map for a small neighbourhood . . . . . . . . .

. . . . . . . .

. . . .

. . . . . . . .

. . . .

. . . . . . . .

. . . .

. . . . . . . .

. . . .

. . . . . . . .

. . . .

. . . . . . . .

. . . .

. . . .

xv

List of Publications  M. Small and K. Judd, `Comparison of new nonlinear modelling techniques with applications to infant respiration', Physica D, Nonlinear Phenomena 117 (1998), 283{298.

 M. Small and K. Judd, `Detecting nonlinearity in experimental data', International Journal of Bifurcation and Chaos 8 (1998), 1231{1244.  M. Small and K. Judd, `Pivotal statistics for non-constrained realizations of composite null hypotheses in surrogate data analysis', Physica D, Nonlinear Phenomena 120 (1998), 386{400. In press.

 M. Small and K. Judd, `A tool for the analysis of periodic experimental data', Physical Review E, Statistical Physics, Plasmas, Fluids, and Related Interdisciplinary Topics. (1999). In press.

 M. Small, K. Judd, M. Lowe, and S. Stick, `Is breathing in infants chaotic? Di-

mension estimates for respiratory patterns during quiet sleep', Journal of Applied Physiology 86 (1999), 359{376.

 M. Small, K. Judd, and A. Mees, `Testing time series for nonlinearity', Statistics and Computing (1998). Submitted.

 M. Small, K. Judd, and S. Stick, `Linear modelling techniques detect periodic

respiratory behaviour in infants during regular breathing in quiet sleep', American Journal of Respiratory and Critical Care Medicine 153 (1996), A79. (abstract, conference proceedings).

 M. Small and K. Judd, `Using surrogate data to test for nonlinearity in experimen-

tal data', in International Symposium on Nonlinear Theory and its Applications, 2, pp. 1133{1136 (Research Society of Nonlinear Theory and its Applications, IEICE, 1997). (conference proceedings).

xvi

xvii Acknowledgements I wish to thank my wife, Sylvia, for encouraging this endeavour, for believing that it was actually worthwhile, and for telling me so when I couldn't see the light. I wish to thank my supervisors, Dr Kevin Judd and Dr Stephen Stick for their invaluable guidance and in nite patience. I gratefully acknowledge Dr Judd's patient explanations of minimum description length, pl timeseries (the radial basis modelling code), and correlation dimension. Without Dr. Stick's initial interest in the application of nonlinear dynamical system theory to the human infant respiratory system, this project would never have commenced. I thank Dr Stick for patiently explaining enough physiology to me to give me a basic grasp of the human respiratory system. I am grateful for the opportunity to conduct data collection during daytime and overnight sleep studies at Princess Margaret Hospital and thank Dr Stick for trusting a (former) pure mathematician with human babies. For much of the data in this thesis I am indebted to Madeleine Lowe and the nursing sta at the sleep lab at Princess Margaret Hospital. Madeleine has been responsible for organised suitable sleep studies, recruiting and running the longitudinal study included in this thesis, and explaining any aspect of human physiology which I still did not understand. I must also thank the nursing sta at Princess Margaret Hospital for accommodating my equipment and research during overnight sleep studies. I wish to thank Professor Alistair Mees for organising regular CADO research meetings, and encouraging the participation of all postgraduate students. I wish to thank my fellow postgraduate students. In particular, I wish to thank David Walker for often pointing out the extreme obvious, and occasionally the not so obvious. I also thank Stuart Allie, for, among other things, explaining the subtleties of LATEX and UNIX. Furthermore, I wish to thank the other postgraduate and former postgraduate students in CADO, the department of mathematics, and the university at large, for, many generally helpful comments and the occasional beer. I would also like to thank Professor Marius Gerber and postgraduate students in the Department of Applied Mathematics at Stellenbosch University for their hospitality and many helpful conversations. I wish to thank the Institute for Child Health Research and the Australian Sudden Infant Death Syndrome Council and acknowledge their nancial support during the initial 12 months of this project. Subsequent funding was provided, through a University Postgraduate Award, by the the University of Western Australia. Finally, I wish to thank my family and friends for all their support. I thank my father in law Mr Lester Lee for lending me his copy of Dorland's Pocket Medical Dictionary for the last three and a half years. I thank my parents for giving me the opportunity to demonstrate that I don't really have to get a real job. I thank my friends, the Reid Co ee shop, and the Broadway Tavern for much co ee, the occasional cigarette, and many beers. For everything else, I again thank my wife.

xviii

1

Part I

Introduction

CHAPTER 1

Exordium Since the popularisation of dynamical systems theory and \chaos" there has been a steady increase in interest in applications of these methods within the biological and medical sciences | most notably in the analysis on electroencephalogram and electrocardiogram recordings. In particular, there is a vast amount of literature on applications of estimates of correlation dimension using (most commonly) the Grassberger and Procaccia algorithm. Figure 1.1 demonstrates the proliferation of work on dynamical systems theory in the medical literature1 since the rst use of \chaos" in its present context, and Grassberger and Procaccia's publication of a correlation dimension estimation algorithm. Rapp, Schmah and Mees [108] provide a compelling argument for the application of modern dynamical systems theory. They argue that traditional models, what they call Newtonian models, are fundamental to most of science since the seventeenth century. These methods are the (di erential) equation based models of (dynamical) systems. One has a set of exact equations describing a dynamical system. It is generally possible to solve these equations and obtain a solution (closed form, series, or numeric). One may then make observations about the original dynamical system from this solution. Unfortunately, arriving at the initial set of equations can be dicult and, in general, one will be unable to do so. The alternative, and the approach we follow here, is to collect data from the dynamical system and arrive at conclusions based on these data. In general one will collect data, build a (numerical) model of these data, and use that model as an approximation to the solution of the obscured Newtonian model. Hence one may: (i) collect data; (ii) model that data set; (iii) con rm the \goodness" of that model by comparing properties of the model to data; and, nally (iv) use that model to deduce properties of a hypothesised generic underlying dynamical system not apparent from data. It is the fourth stage of this process that is most important and can lead to insight about the original system. This thesis presents an analysis of the respiration of sleeping human infants, using, primarily, the techniques of dynamical systems theory. Despite the mass of work on the applications of these methods to the analysis of electroencephalogram and electrocardiogram data, work on the dynamical system theoretic analysis of the human respiratory system is far from comprehensive. Previous studies of the analysis of human respiration using these techniques have mainly centred on estimates of correlation dimension. These studies conclude that the infant respiratory system is either possibly chaotic or de nitely not and do so in about equal proportions. As Rapp [107] observed, to conclude that a phenomenon is chaotic is both dicult and often irrelevant. The These data are based on keyword searches using Medline. Medline is an electronic catalogue of scienti c journals produced by the United States National Library of Medicine. It covers topics including clinical medicine and physiology, and catalogues over 3600 journals. 1

3

4

Chapter 1. Exordium "chaos"

Dimension Estimates

350

150

300 250

100

200 150 50

100 50 0 1970

1980

1990

2000

0 1970

1980

1990

2000

Figure 1.1: Publications of dynamical systems theory in medical literature: The number of publications by year in the medical literature on applications of dynamical systems theory. The plot on the left is for all papers containing one of the phrases \chaos", \chaotic", or \nonlinear dynamics" (in the title or abstract) in the medical journals indexed by Medline. The entry for 1974 (the rst entry) includes all publications over the period 1963{1974. A number of these publications may be references to \chaos" in another context | this author makes no claim about the content of all of these publications. The plot on the right shows the number of publications containing the phrase \correlation dimension" or \fractal" over the same period. Grassberger and Procaccia's paper [44] on estimation of correlation dimension was published in 1983. It is far less likely that either \correlation dimension" of \fractal" could be used in any other context. Both plots show an exponential growth in publications. However, one must bear in mind that publication bias would limit the number of publications in any new eld. e ect of a nite amount of data corrupted by noise can make the accurate estimation of correlation integral based dynamic measure both dicult and unreliable. In this thesis we identify nonlinearity within normal respiration, build numerical models from data collected from sleeping infants, and deduce properties of the respiratory system from these models. In addition to dynamical systems theory and nonlinear modelling techniques we employ the method of surrogate data. Surrogate data techniques can be used to generate a probability distribution of test statistic values to test the hypothesis that observed data were generated by various classes of linear systems. The major results of this thesis concern: (i) the application of a new correlation dimension estimation algorithm; (ii) the application of existing surrogate data techniques; (iii) improvements to existing modelling algorithms to produce satisfactory nonlinear models of respiratory data; (iv) nonlinear surrogate data in general and a new type of nonlinear surrogate data based on nonlinear models; (v) the application of nonlinear

1.1. Dynamics of respiration

5

surrogate data as a form of hypothesis testing to respiratory data; (vi) a new linear modelling technique and the application of this technique to detect cyclic amplitude modulation in respiratory data; and (vii) the application of techniques of dynamical systems theory utilising the information contained in models of those data. We show that the respiration of infants during sleep is inconsistent with simple linear models, or models with correlation only within a single cycle. We show that complex nonlinear modelling algorithms can produce models which are consistent with the respiratory system of sleeping infants. We use correlation dimension to show that this system has two or three dimensional attractor with additional high dimensional small scale structure. This two or three dimensional attractor is consistent with a model of respiration as a periodic orbit with quasi-periodic amplitude modulation. We show that the dynamical systems which we use to model respiration are characterised by a stable focus and a stable periodic or quasi-periodic orbit. This quasi-periodic orbit exhibits a rst return map with either a stable focus a periodic orbit or chaos. Using nonlinear models and linear models derived from information theory we demonstrated that cyclic uctuations in the amplitude of the respiratory signal cyclic amplitude modulation (CAM) is ubiquitous but only usually evident in long time series or during episodes of periodic-type breathing. We show that CAM exhibits a period similar to that of periodic breathing (Cheyne-Stokes respiration) and is more commonly observed in the quiet (non-apneaic) respiratory traces of infants su ering from pronounced central apnea than of normals. Whilst for infants with bronchopulmonary dysplasia CAM is most common during time series which exhibit apnea. We also present evidence of stretching and folding type chaotic dynamics (similar to that exhibited by the Rossler system) in some models of respiration and period doubling bifurcations in the rst return map. In section 1.1 we present a brief review of the respiratory system and the application of mathematical techniques to the analysis of this system. Section 1.2 describes the experimental protocol and summarises the data we have collected, and section 1.3 provides an outline for the body of this thesis.

1.1 Dynamics of respiration In this section we present a brief review of the human respiratory system and a small amount of associated medical terminology. We review some of the extensive literature on the applications of dynamical system theory to physiological system. Finally, we describe some of the traditional mathematical methods used to analyse this system and the physiological motivation for our approach.

1.1.1 Physiology Respiration is the complex process by which oxygen is inhaled

and carbon dioxide is exhaled. The purpose of this section is not to describe this process in detail, but to provide an overview of the important points for the present discussion. For more detail see, for example, [53, 72]. For a more technical discussion see [59].

6

Chapter 1. Exordium

The lungs are surrounded by three muscle groups: the diaphragm, the intercostal muscles, and the abdominal muscles. The diaphragm separates the thoracic and abdominal cavities of the body. The intercostal muscles are situated in the rib cage and the abdominal muscles in the abdomen. All three groups of muscles contract and relax in response to neuronal stimulation. The air, sucked into the lungs by these three muscles, exchanges oxygen and carbon dioxide with the blood through approximately 3  108 alveoli. The alveoli are cell sized pits in the walls of the lungs at which the capillaries (connecting arteries and veins) meet with air in the bronchial tree. Both the bronchial tree and the complex network of ever thinning arteries and veins that terminate and meet at the capillaries are often cited examples of fractal structure in nature [167]. The actual process of respiration, gas exchange and ow of blood and respiratory gases in the lungs can be modelled by relatively simple mathematical equations | see for example [54]. In the remainder of this section we discuss a popular and generally accepted physiological model of neuronal and chemical control of respiration. The nature of the generation of respiratory pattern within the central nervous system is unknown. However, the e ect of various groups of respiratory neurons in the brain stem can be deduced by experimental procedures involving the removal or severing of various portions of the brain stem in laboratory animals (for example [118]). Furthermore, the ring of neurons, coincident with various phases of respiration can be observed in a laboratory. Three distinct regions of the brain stem are known to a ect respiratory control: the pons varolli, the medulla oblongata, and the spinal cord. These three sections are located at the base of the brain. The pons (pons varolli) connects the cerebrum, cerebellum and medulla oblongata. The medulla (medulla oblongata) sits directly above the spinal cord. Within the medulla there are two groups of neurons related to respiratory pattern generation: the dorsal respiratory group, and the ventral respiratory group. The pontine respiratory group of neurons, situated in the pons, are also known to e ect respiration. In both the ventral and pontine respiratory group it is possible to identify clusters of neurons that discharge during either the inspiratory or expiratory phase of respiration. The neurons within the dorsal group are predominantly inspiratory neurons, together with another group of neurons which re in response to the in ation of the lungs. The pontine respiratory group also contains a group of neurons that (unlike the other groups) re during both inspiratory and expiratory respiratory phase. The e ect of these neurons within the pontine respiratory group is not known. The excitation of neurons within the pons and medulla is communicated to the respiratory muscles via the spinal cord. Within the spinal cord there are three separate pathways of respiratory neurons. The potentials of the inspiratory and expiratory neurons in the pons and medulla is transmitted along the automatic rhythmic respiratory pathway to the muscles of respiration: the diaphragm, the intercostal, and the abdominal muscles. A second pathway in the corticospinal tract, the voluntary respiratory

1.1. Dynamics of respiration

7

pathway is associated with voluntary (conscious) respiratory action. A third pathway, the automatic tonic respiratory pathway, located adjacent to the automatic rhythmic respiratory pathway, has unknown e ect. This completes a discussion of the transmission from brain stem to lung of the respiratory pattern. However, the system is further complicated by a form of feedback loop. The vagus (or vagal nerve) is the tenth (of twelve) major cranial nerves and originates from the medulla oblongata. The vagal nerve splits into thirteen branches including the bronchial, superior laryngeal, and recurrent laryngeal nerves which terminate at the bronchi, the larynx, and the pharynx respectively. Pulmonary stretch receptors located in the bronchi and trachea sense the state of muscle tone, and therefore air ow, in these areas. This information is transmitted, indirectly, back along the vagus to the brain stem and the respiratory motor neurons located there. The phenomenon of the vagus as a form of feedback mechanism is well known, its exact e ect is not. Sammon [118] has shown that the correlation dimension of respiratory activity decreases in rats after vagotomy. In addition to feedback via the vagal nerve of information concerning air ow in the trachea the respiratory system receives input from other sources including the peripheral arterial chemoreceptors. The peripheral arterial chemoreceptors are located on the common carotid artery at the point where it splits into two. The carotid artery is connected via the aorta to the left ventricle of the heart. These chemoreceptors measure the concentration of oxygen in the blood and transmit this information to the respiratory pattern generator in the brain stem. There are also many other e ects on respiration including, for example, temperature dependent e ects which have been hypothesised to be related to incidence of sudden infant death [33]. Hence, the ring of neurons in the pons and medulla generate potentials that are transmitted through the spinal cord to the muscle surrounding the lungs. The lungs, acting as a set of bellows draw air into and expel it from them. Whilst in the lungs, oxygen is absorbed from the air and carbon dioxide is disgorged from the blood. The air

ow through the bronchi and trachea, and the oxygen concentration in the blood e ect pulmonary stretch receptors and chemoreceptors. These receptors indirectly transmit this information via the vagus back to neurons in the brain stem. Additional information concerning the environment and the state of activity of an individual also, indirectly act on the respiratory motor neurons in the brain stem. The exact manner in which respiratory pattern is generated in the central nervous system is not known. The purpose of the automatic tonic respiratory pathway in the spinal column and some groups of respiratory neurons in the pons and medulla are also unknown.

1.1.2 Pathology Finally, we move from a discussion of control of respiration to

highlight several important phenomena often evident in infants. The rst is periodic

8

Chapter 1. Exordium Ms2t4 6 4 2 0 −2 0

50

100 time (sec.)

150

200

Figure 1.2: Periodic breathing: An example of periodic breathing in an infant. At approximately 110 seconds the respiratory pattern switches from regular quiet breathing to periodic breathing. or Cheyne-Stokes breathing. Periodic breathing is the regular periodic uctuation in the amplitude of respiration from zero to normal respiratory levels. This phenomenon typically occurs over a period of 10{20 seconds and is common during sleep for healthy infants. There is, however, some evidence that infants with near miss sudden infant death have abnormally high levels of periodic breathing [66]. Secondly, sleep apnea is the cessation of breathing for a period of several seconds during natural sleep. There are two distinct types of apnea, central apnea and obstructive apnea. Central apnea is caused by the muscles of the lungs stopping the normal rhythm because of lack of input from the neural pattern generator. Obstructive sleep apnea is caused by a blockage of the airway and is often associated with snoring. Central apnea is of far greater relevance to a study of the control of breathing. Again, short apneaic episodes are not uncommon in normal, healthy infants. Some factors that have been shown to contribute to increased apnea include an increase body temperature and sleep deprivation [40]. Finally, bronchopulmonary dysplasia (BPD) is a common phenomenon among infants | particularly as a complication in the treatment of respiratory distress syndrome (RDS). Respiratory distress syndrome is caused by an infant being born whilst the respiratory system is still incapable of functioning outside the womb. This is usually treated with forms of arti cial respiration, respiratory aids or the administration of oxygen. A common side e ect of this treatment is bronchopulmonary dysplasia. Infants exhibiting bronchopulmonary dysplasia will generally have respiratory diculty and insucient oxygenation of the blood [72].

1.1.3 Chaos and physiology As gure 1.1 demonstrates there is a plethora

of publications on various applications of dynamical systems theory in general, and correlation dimension speci cally, to physiological systems. In this section we do not o er a complete review of this literature. Instead we present a representative selection of publications across the elds of medicine and physiology along with some more exotic

1.1. Dynamics of respiration

9

applications. The majority of papers published in this eld | especially less recent publications | concentrate on the estimation of correlation dimension, or some variant. Particularly, in electroencephalography and clinical neurophysiology correlation dimension has become a common tool of analysis, for example [3, 10, 52, 87, 94, 105, 111, 112, 146, 151, 154]. In particular, the paper of Theiler [151] and Theiler and Rapp [154] o ers a critical appraisal of the techniques of dimension estimation and the application of surrogate data techniques. Birbaumer and others [10] have compared correlation dimension estimates of electroencephalogram signals whilst listening to classical and contemporary music | and concluded that classical music generates a response with higher correlation dimension. There is also large number of publication on the analysis of electrocardiographic signals [9, 38, 39, 56, 88, 128, 129, 132, 147, 156, 158, 168]. A paper from Storella and colleagues [147] gives a simple demonstration of the e ectiveness of these techniques. In this paper, Storella and colleagues show that the response of complexity and variance of heart rate variability to anaesthesia are di erent and demonstrate the complexity is more sensitive to changes in the cardiovascular system than heart rate variability. Gar nkel and others [38, 39] have demonstrated an e ective method for controlling cardiac arrythmias induced in rabbits. The implications of these methods for patients with heart conditions is signi cant [22]. Estimation of correlation dimension has also found application in the analysis of uctuations in blood pressure [165], characterising the behaviour of the olfactory bulb [130, 131], and in analysis of optokinetic nystagmus [123], parathyroid hormone secretion [100] and diastolic heart sounds [91]. Ikeguchi and colleagues have analysed the dimensional complexity of Japanese vowel sounds [58]. Apart from correlation dimension estimation other studies have estimated the entropy of physiological process [83, 96] and the entropy of rat movement in a con ned space [93]. Lippman and colleagues [78, 79] have applied the techniques of nonlinear forecasting to electrocardiogram signals. Using these methods they \clean" the electrocardiographic data of abnormal heart beats [78], and apply nonlinear forecasting as a form of characterisation of electrocardiograms [79]. Hoyer and others [56] also apply methods of nonlinear prediction. Of course, there is also a substantial amount of literature concerning the analysis of respiratory signals using the techniques of nonlinear dynamical systems theory [16, 17, 23, 32, 35, 95, 114, 115, 116, 117, 118, 166]. Donaldson [23] used estimates of Lyapunov exponents to conclude that resting respiration is chaotic. However, this study was unable to distinguish a nonlinear dynamical system from linearly ltered noise. Pilgram [95] presents an analysis of correlation dimension estimates during REM sleep and utilises linear surrogate techniques. This study concluded that breathing during REM sleep is chaotic.

10

Chapter 1. Exordium

Webber and Zbilut [166] demonstrate the application of recurrence plot techniques to respiratory and skeletal motor data. Cleave and colleagues [16, 17] present a theoretical analysis of the respiratory response to a sigh [16], and demonstrate the existence of a Hopf bifurcation in a feedback model of respiration [17]. A similar analysis of the response of the respiratory system to sighs [32] tted a second order damped oscillator to response curves. Fowler and colleagues [35] have proposed a singular value decomposition type method to lter respiratory oscillations. Sammon and colleagues [114, 115, 116, 117, 118] give a comprehensive analysis of respiration in rats and the e ect of vagotomy on this respiration. From their observations they concluded that, in anaesthetised, vagotomised, rats the respiratory system behaves as an oscillator with a single degree of freedom. With the vagus intact however, respiratory behaviour was more complex, exhibiting low-order chaos which the authors speculated, was due to feedback from various types of pulmonary a erent activity.

1.1.4 Mathematical models of respiration The simplest models of the respi-

ratory system are those of gas exchange in the lungs [54]. One can model the absorption of oxygen into, and the excretion of carbon dioxide from the blood in the lungs. These models are based on the ideal gas law, rates of absorption and solubility between gas and liquid, and conservation of matter. These simple equations provide a good model of the exchange between gases in air and blood in the lung. Models of the control of respiration which explain observable phenomena such as periodic breathing are more sophisticated. Fundamental to many such models is an oscillatory driving signal, a group of neurons or a cerebral control centre. This provides the driving force for the respiratory motion. Such a model was proposed by van der Pol in 1926 [157] 2 and latter generalised [31]. Some form of periodic orbit, or Hopf bifurcation (for example [17]), is central to many models of respiration. The Mackey-Glass equations [81] are rst order delay di erential equations which model physiological systems. These equations were proposed in a general context and were shown to exhibit qualitative features of respiration, including Cheyne-Stokes respiration (periodic breathing). An extension to this system which takes into account the cerebral control centre driving respiration has also been shown to provide similar results [74]. Sammon [114] gives a detailed analysis of a second order ordinary di erential equation for the central respiratory pattern generator and shows that the eigenvalues of a xed point of that system can generate a variety of behaviours consistent with respiration. In another paper Sammon presents a more complex multivariate model of the Van der Pol's discussion was in the general context of \relaxation oscillators, particularly in electric circuits and cardiac rhythm. 2

1.1. Dynamics of respiration

11

respiratory pattern generator [115]. Others have proposed damped oscillator models of the respiratory response to a sigh [16, 32] and feedback models of the respiratory system [17]. In a series of papers Levine, Cleave and colleagues [16, 17, 77, 76] have proposed successive di erential equation models of the respiratory system. Their simplest model [16, 17] incorporated blood gas concentration feedback and was represented by three di erential equations. This model exhibited Hopf bifurcations under some circumstance [17]. Subsequent models incorporated ve [77] and eight [76] di erential equations. These models indicate that periodic breathing was a consequence of small changes in model parameters, and may be a reaction to hypoxic conditions. Decreased oxygenation was shown to trigger the onset of periodic breathing. The majority of work in modelling respiration appears in the bioengineering literature, [68] provides an overview of some recent developments. Many of these studies model the concentration of gases in blood and not the respiratory motion of the lungs. Hoppensteadt and Waltman [55] proposed a model of carbon dioxide concentration in blood which was able to mimic some qualitative features of Cheyne-Stokes breathing. A similar model of carbon dioxide concentration was also reported by Vielle and Chauvet [159]. Cooke and Turi [20] have suggested a simple delay equation model of respiratory control and present an analysis of that model of the respiratory control system. A control system model of respiration is also described by Longobardo and colleagues [80]. This model was able to reproduce some qualitative features of sleep apnea and Cheyne-Stokes breathing. Grodins and colleagues [46] describe a complex series of di erential and di erence equations modelling gas transportation and exchange, blood ow, and ventilatory behaviour. A computer implementation of these equations was able to produce some qualitative features of the respiratory system. Finally, Khoo and others [69, 70] have presented general models of periodic breathing as a result of respiratory instability. All these models are based on equations governing various physical processes. These equations are determined by the investigators and based on what they consider appropriate characteristics of the system. However, the respiratory system, its neuronal control and the e ect of other external and internal forces is doubtless more complicated than any of these models. Our approach is somewhat di erent. We use a model construction method based upon the fundamental theorems of Takens (see section 2.1). By assuming the presence of a Markov process other authors have constructed hidden Markov models [26, 71] of data. Coast and colleagues [18, 19] have applied hidden Markov models to electrocardiographic signals during arrhythmia. By building hidden Markov models of di erent types of beats exhibited by the electrocardiogram signals of one subject they were able to calculate the most likely model for a given (new) beat and use this to classify heart beats. Radons and colleagues [106] have applied similar methods to the analysis of electroencephalogram measurements of a monkey's

12

Chapter 1. Exordium

visual cortex. In this study hidden Markov models were used to classify the response to di ering visual stimuli of a 30 electrode array implanted in a monkey's visual cortex. Altenatively, nonlinear stochastic time series models with a feedback device may be employed to model respiratory oscillations. These techniques are described by Priestly [103]. Priestly connects a threshold autoregressive process and bilinear models using feedback. These techniques may adequately mimic the irregular almost periodic oscillations observed in respiratory oscillations. An approach similar to those described above could be employed here, however we do not employ these methods but build radial basis models. Radial basis models are more compliant to the techniques of nonlinear dynamical systems theory. There have been many published works demonstrating the application of the radial basis modelling techniques utilised in this thesis, to dynamical systems theory. Judd and Mees [62] demonstrate the application of radial basis modelling to the modelling of sunspot dynamics. In a very recent paper [64] they apply radial basis modelling techniques to model sunspot dynamics and Japanese vowel sounds. Cao, Mees and Judd [13] have demonstrated the application of these method to modelling and predicting with nonstationary time series. Finally, Judd and Mees [63] demonstrates the presence of a Shil'nikov bifurcation [124, 125, 126] mechanism in the chaotic motion of a vibrating string.

1.1.5 Periodic respiration In section 1.1.2 we described the physiological phe-

nomenon known as periodic breathing. In chapter 9 we will introduce a new technique to detect faint periodic patterns in noisy time series and demonstrate that cyclic uctuations in the amplitude of respiration during normal quiet sleep is a ubiquitous phenomenon. Hence it is relevant at this stage to brie y review other researchers e orts to detect cyclic uctuation in the amplitude of respiration. Fleming and co-workers [32, 34] demonstrated age dependent periodic uctuation in amplitude in response to a spontaneous sigh in infants. This was achieved by tting di erential equations modelling a decaying oscillator to the experimentally measured response. They found that the period of oscillations increased with age and the damping increases then decreases. Brusil, Waggener and colleagues [11, 12, 162, 160, 164, 161] applied a comb lter technique to detect periodic uctuations of amplitude in the respiration of adults at simulated extreme altitude [12, 160] and in premature infants [162, 164, 161]. They found that in premature infants the period of uctuations was related to the duration of apnea. The comb lter technique they applied was a series of course grained band pass lters applied to a synthetic signal derived from abdominal cross-section recordings. The comb lter is e ectively equivalent to a frequency averaged Fourier spectral estimate. In another series of studies Hathorn [49, 50, 51] investigated periodic changes in ventilation of new born infants (less than one week old). Hathorn applied Fourier

1.1. Dynamics of respiration

13

spectral and autocorrelation estimates to quantify amplitude and frequency uctuations. Furthermore, using a sliding window technique they investigated the e ects of non-stationarity. By splitting the frequency components of ventilation into high and low frequency Hathorn showed a stronger coherence between respiratory oscillations and heart rate in quiet sleep [51]. Hathorn's investigations were based on analysis of time/breath amplitude analysis whereas the analysis we perform in this thesis is of breath number/breath amplitude data. Furthermore, the infants we examine in this study vary over a wider range of ages (up to six months). Finley and Nugent [29] applied spectral techniques to demonstrate that new born infants exhibit a frequency modulation in normal respiration (during quiet sleep) of approximately the same frequency as periodic breathing. A series of other studies by other various groups [30, 43, 75, 101] have also demonstrated some periodic uctuations in amplitude of respiratory e ort in either resting adults [43, 75, 101] or sleeping infants [30].

1.1.6 Motivation The simplest model of respiratory control is described in sec-

tion 1.1.1. Respiration is governed by discrete \pacemaker" cells with intrinsic activity that drives other respiratory neurons. The output of various respiratory centres or pools of motor neurons is then organised by a pattern generator. An alternative approach implies that networks of cells with oscillatory behaviour interact in a complex way to produce respiratory rhythms which are either further organised by a pattern generator or might be self-organising [28]. The purpose and behaviour of many groups of neurons in the respiratory control centres and there interaction is still unknown and so this approach is essentially a further complication of the description given in section 1.1.1. Advances in neurobiology have allowed recordings to be made from individual neurons and groups of neurons in the brain. Using these techniques, various studies have demonstrated that the concept of discrete respiratory centres made up of neurons with speci c functions de ned by the nature of a particular \centre" is obsolete [28]. Whilst there is organisation of neurons into functional networks or pools these are not necessarily anatomically discrete. Also, there are con icting data in regard to the presence of a speci c pattern generator. Given the complexity of the connections between the various groups of oscillating, respiratory-related neurons, and the capacity for interactions between simple oscillating systems to produce complex behaviour, we believe that information about the organisation of respiratory control can be determined using dynamical systems theory. In essence, the argument that there is a simple \pattern generator" that co-ordinates the output from various \respiratory centres" is unnecessary if the output from interacting networks is dynamical and self-organising. Other authors have applied techniques derived from dynamical system theory to respiratory systems with some success. These studies are summarised in sections 1.1.3 and 1.1.4. In particular, Cleave and colleagues [17] have demonstrated the possible

14

Chapter 1. Exordium

existence of Hopf bifurcations in the response of the respiratory system to sighs. Sammon and others [114, 115, 116, 117, 118] give a comprehensive analysis of respiration in rats using the techniques of dynamical system theory. Numerous other authors have presented evidence of chaos in correlation dimension and Lyapunov exponent estimates for respiratory data. Recent physiological studies [57] have suggested that immature or abnormal development of the respiratory control centres in the brain stem may be a contributing factor to sudden infant death syndrome (SIDS). It is hypothesised [57] that infants at risk of SIDS do not have a properly developed respiratory control and are therefore unable to respond to pathological and physiological stresses (such as hypoxia, airway obstruction, and hypercapnia). However this study has been unable to nd distinctions between \normal" and \at risk" infants which can be used to diagnose risk of sudden infant death. This method has been unable to detect subtle variation between subjects which the techniques of nonlinear dynamical system theory may.

1.2 Data collection The experimental protocol of all the studies described in this thesis are basically identical. For these studies we collected measurements proportional to the cross-sectional area of the abdomen of infants during natural sleep. To do this we used standard noninvasive inductive plethysmography techniques which will be described in more detail latter. Such measurements are a gauge of lung volume. The abdominal signal is not necessarily proportional to lung volume but the signal is sucient for our purposes3 . Moreover, present methods are not capable of dealing well with multichannel data and therefore use of both rib and abdominal signal to approximate actual lung volume is dicult. Of the available measurements we found that the abdominal cross section was the easiest to measure experimentally. These studies were conducted in a sleep laboratory during day time and overnight sleep studies at Princess Margaret Hospital for Children4 . These studies had approval from the ethics committee of Princess Margaret Hospital and the University of Western Australia Board of Postgraduate Research Studies. The parents of the subjects of these studies were informed of the procedure, and its purpose, and had given consent.

1.2.1 Experimental methodology An inductance plethysmograph provides a

non-invasive measurement of cross-sectional area. It consists of a thin wire loop wrapped in an elasticised band. This is placed (in this study) around the abdomen of a sleeping infant. A small electrical (AC) voltage potential is created at the ends of this wire

Takens' embedding theorem [148] (and therefore the methods of this chapter, see section 2.1) only require a C 2 (smooth) function of a measurement of the system. 4 Department of Respiratory Medicine, Princess Margaret Hospital for Children, Subiaco, WA, Australia 6008. 3

15

1.2. Data collection

generating an alternating current in the loop. Voltage v and current { in an inductor are related by [89] v = d(L{) (1.1)

dt

where L is the inductance. Inductance in a wire loop is given by [89]

L = A `

(1.2)

where A and ` are the area enclosed by, and length of, the wire. The permeability  is a constant electromagnetic property of the medium. Substituting (1.2) into (1.1), one gets   dA d{  v = ` dt { + A dt :

Let { = I0 cos ( 2! t) where ! is the frequency of the alternating current source, and so,  !   !   dA ! v = ` I0 dt cos 2 t ; A 2 sin 2 t : Let v = V0 cos ( 2! t + ), and a trivial trigonometric identity yields V0 cos  = ` I0 dA dt  V0 sin  = ` I0A 2!

and therefore

s

 2 I 0 2 2 2 (1.3) V0 = 2` A ! + 4 dA dt : 0 A! so V0  I2` . Hence, the magnitude of the current is inversely

However A!  2 dA dt proportional to the cross sectional area of the wire loop. In addition to the inductance plethysmograph, polysomnographic criterion are used to score sleep state [7]. A polysomnogram consists of a series of separate pieces of equipment to measure eye movement, brain activity, respiration, muscle movement and blood gas concentrations. Typically a polysomnogram consists of electroencephalogram (EEG), electrooculogram (EOG), electromyogram (EMG) and electrocardiogram (ECG) to measure brain activity, eye movement, muscle tone and heart rate. An oximeter is employed to measure blood oxygen saturation (the concentration of oxygen in the blood), nasal and oral thermistors measure temperature change at nose and mouth (this is related to the quantity of air exhaled), and plethysmography is used to record rib and abdominal movement. For a detailed discussion of sleep studies see [85]. The un ltered analogue signal from the inductance plethysmograph5 is passed through a DC ampli er and 12 bit analogue to digital converter (sampling at 50Hz). Non-invasive Monitoring systems, (NIMS) Inc; trading through Sensor medics, Yorba Linda, CA., USA. 5

16

Chapter 1. Exordium

The digital data were recorded in ASCII format directly to hard disk on an IBM compatible 286 microcomputer using LABDAT and ANADAT software packages6 . These data were then transferred to Unix workstations at the University of Western Australia for analysis using MATLAB7 and C programs. By amplifying the output of the inductance plethysmograph before digitisation our data occupy at least 10 bits of the AD convertor. Hence, error due to digitisation is less than 2;11 < 0:0005. Errors due to the approximation involved in the derivation of (1.3) are substantial less than digitisation e ects. Our data are sampled at 50Hz, however, tests at higher sampling rates indicate that there is no signi cant aliasing e ect. The only practical limitation on the length of time for which data could be collected is the period that the infant remains asleep and still. The cross sectional area of the lung varies with the position of the infant. However, in this study we are interested only in the variation due to the breathing and so we have been careful to avoid artifact due to changes in position or band slippage. We have made observations of up to two hours that are free from signi cant movement artifacts, although typically observations are in the range ve to thirty minutes.

1.2.2 Data The data collected for this thesis consists primarily of two sections.

A longitudinal study was conducted with nineteen healthy infants studied at 1, 2, 4 and 6 months of age. These studies were performed exclusively during the day. Data from this study we designate as group A. In a separate study, a group of 32 infants and young children admitted to Princess Margaret Hospital were studied during overnight sleep studies arranged for other purposes. Of these subjects 28 were under 24 months of age. Most were su ering from either bronchopulmonary dysplasia (8 of 32) or central (13) or obstructive (4) sleep apnea. These data are subdivided according to the clinical reasons for the sleep study. Infants su ering from clinical apnea we designate as group B, those with bronchopulmonary dysplasia we designate as group C, the remainder are group D.

1.3 Thesis outline This thesis is organised into four separate parts: (I) this introduction; (II) a summary of the required mathematical background; (III) the analysis of infant respiration; and (IV) the conclusion. Part II contains two chapters, chapter 2 covers background material from the eld of nonlinear dynamical systems theory. Chapter 2 describes general reconstruction techniques, Takens' embedding theorem, correlation dimension, correlation dimension estimation, and radial basis modelling. The second part of this summary, chapter 3, 6 7

RHT-InfoDat, Montreal, Quebec, Canada. The Math Works, Inc., 24 Prime Park Way, Natick, MA., USA.

1.3. Thesis outline

17

describes the method of surrogate data and summarises some terminology and theory commonly applied in the literature. Part III is the dynamical systems analysis of respiration in human infants during natural sleep. This part describes the methods employed, the theory developed and the results obtained. All of the new results of this thesis are described in this part. Part III of the thesis is split into eight chapters. Chapter 4 concerns surrogate data techniques. This chapter describes various methods of surrogate generation and provides some comparison between them. Some general theory concerning the pivotalness of correlation dimension estimates is developed and some numerical calculations con rming these results is presented. In this chapter we present a new result concerning the conditions which ensure a test statistic is pivotal. Using this result we show many statistics based on dynamical system theory are asymptotically pivotal. In particular, we demonstrate that correlation dimension estimated using the algorithm described by Judd [60, 61] provides a pivotal test statistic for classes of linear and nonlinear surrogates. In chapter 5 we provide a brief summary of the application of various methods described in section 2.1 to choose the parameters of time delay embeddings. The results of this section are primarily concerned with demonstrating the estimation of embedding parameters for respiratory data using existing techniques. For two dimensional embeddings we apply a novel approach to demonstrate the dependence on the shape of the embedded data on embedding parameters. We use this to suggest an appropriate value of embedding lag. The modelling methods developed for this thesis are discussed in chapter 6. This chapter also describes the e ectiveness of the modelling method employed. This chapter develops the necessary theory and methodology to describe the modelling methods we employ. We show that successive alterations to an earlier modelling algorithm eventually produce models which exhibit many qualitative and quantitative similarities to data. The modelling algorithm is based on methods discussed by Judd and Mees [62], however the application of this algorithm to respiratory recordings and the alterations to this algorithm are original. Using these new improvements to this existing algorithm we are able to demonstrate CAM during quiet breathing and show that it has the same period as periodic breathing following a sigh. Chapter 7 describes, in more detail, some results of the application of the modelling methods of chapter 6. This chapter analyses the nature of the dynamics present in the models of respiratory data and presents evidence of period doubling bifurcations in some models of infant respiration. Evidence of stretching and folding of trajectories is also presented. The results presented in this chapter are a new application of existing techniques of dynamical systems theory to the analysis of nonlinear models. By analysing properties of cylindrical basis models we are able to infer characteristics of the dynamical system which generated the observed data.

18

Chapter 1. Exordium

The results of chapter 8 are based largely on a paper published in the physiological literature. This chapter describes the analysis of infant respiration using the tools we have developed and described so far. We use correlation dimension estimation, linear and nonlinear surrogate analysis and cylindrical basis modelling to conclude that infant respiration is likely to be a two to three dimensional system with at least two periodic (or quasi-periodic) driving mechanisms and additional complexity. Furthermore, this system is modelled well by the cylindrical basis modelling methods we describe. The application of these methods to the analysis of infants respiration and the conclusions we reach are new. Chapter 9 describes calculations to detect this second periodic source (the cyclic amplitude modulation) present in the infant respiratory system. This chapter employs new linear modelling techniques derived from the nonlinear modelling methods described in chapter 6 and information theoretic measurement of \structure" described in that chapter. These calculations detect the presence of a cyclic amplitude modulation of approximately the same period as periodic breathing and we conclude that this phenomenon represents a ubiquitous driving mechanism present during regular respiration but most notable only during periodic breathing. This is the rst evidence of the presence of CAM during quiet respiration in all infants. Finally, chapter 10 describes the application of nonlinear methods: Floquet theory and Poincare sections to detect cyclic amplitude modulation from models of respiration. The results of this chapter con rm an earlier assertion that the respiratory system exhibits a periodic, or quasi-periodic amplitude modulation. In data where cyclic amplitude modulation is not evident the rst return map exhibits a stable focus. The nal part of this thesis contains one section and is a summary and conclusion.

19

Part II

Techniques from dynamical systems theory

21

CHAPTER 2

Attractor reconstruction from time series In this chapter we describe the reconstruction of an unknown dynamical system from data. The general techniques described here may be found in many references: [2] discusses reconstruction techniques and [98] is a summary of radial basis modelling techniques. In section 2.1 we describe attractor reconstruction and Takens' embedding theorem. Section 2.2 is a discussion of correlation dimension estimation and section 2.3 is concerned with radial basis modelling and description length [110]. In chapter 3 we will review existing hypothesis testing methods using surrogate data.

2.1 Reconstruction Attractor reconstruction using the method of time delays is now widely applied, we will brie y describe the key points of this technique and the methods we utilise to select an appropriate embedding strategy. Let M be a compact m dimensional manifold, Z : M 7;! M a C 2 vector eld on M , and h : M 7;! R a C 2 function (the measurement function). The vector eld Z gives rise to an associated evolution operator ( ow) t : M 7;! M . If zt 2 M is the state at time t then the state at some latter time t +  is given by zt+ =  (zt ). Observations of this state can be made so that at time t we observe h(zt ) 2 R and at time t +  we can make a second measurement h( (zt)) = h(zt+ ). Taken's embedding theorem [148] guarantees that given the above situation, the system generated by the map Z;h : M 7;! R2m+1 where Z;h (zt ) := (h(zt); h( (zt)); : : : ; h(2m (zt))) (2.1) = (h(zt); h(zt+ ); : : : ; h(zt+2m )) is an embedding. By embedding we mean that the asymptotic behaviour of Z;h (zt) and zt are di eomorphic. We can apply this result to reconstruct from a time series of experimental observations fyt gNt=1 (where yt = h(zt )) a system which1 is (asymptotically) di eomorphic to that which generated the underlying dynamics. We produce from our scalar time series

y1 ; y2; y3; : : :; yN a de -dimensional vector time series via the embedding (2.1)

yt; 7;! vt = (yt; ; yt;2 ; : : : ; yt;de )

8t > de:

To perform this transformation one must rst identify the embedding lag  and the embedding dimension de 2 . We describe the selection of suitable values of these parameters Subject to the usual restrictions of nite data and observational error. A sucient condition on de is that it must exceed 2m + 1 where m is the attractor dimension. However, to estimate m, one must already have embedded the time series. Any values of  is theoretically acceptable, however, for nite noisy data it is preferable to select an \optimal" value. 1 2

22

Chapter 2. Attractor reconstruction from time series

in the following paragraphs. An embedding depends on two parameters, the lag  and the embedding dimension de . For an embedding to be suitable for successful estimation of dimension and modelling of the system dynamics, one must choose suitable values of these parameters. The following two subsections discuss some commonly used methods to estimate embedding lag  and embedding dimension de .

2.1.1 Embedding dimension de Takens embedding theorem [90, 148] and more

recently work of Grebogi [21]3 give sucient conditions on de . Unfortunately, the conditions require a prior knowledge of the fractal dimension of the object under study. In practice one could guess a suitable value for de by successively embedding in higher dimensions and looking for consistency of results; this is the method that is generally employed. However, other methods, such as the false nearest neighbour technique [27, 150], are now available to suggest the value of de . False Nearest Neighbours Suitable bounds on de can be deduced by using false nearest neighbour analysis [67]. The rationale of false nearest neighbour techniques is the following. One embeds a scalar time series yt in increasingly higher dimensions, at each stage comparing the number of pairs of vectors vt and vtNN (the nearest neighbour of vt) which are close when embedded in Rn but not close in Rn+1 . Each point

vt = (yt; ; yt;2 ; : : : ; yt;n ) has a nearest neighbour

vtNN = (yt0 ; ; yt0;2 ; : : : ; yt0;n ): When one has a large amount of data the distance (Euclidean norm will do) between vt and vtNN should be small. If these two points are genuine neighbours then they became close due to the system dynamics and should separate (relatively) slowly. However, these two points may have become close because the embedding in Rn has produced trajectories that cross (or become close) due to the embedding and not the system dynamics4 . For each pair of neighbours vt and vtNN in Rn one can increase the embedding dimension by one so that

vbt = (yt; ; yt;2 ; : : : ; yt;n ; yt;(n+1) ) and NN vd t = (yt0 ; ; yt0;2 ; : : : ; yt0 ;n ; yt0 ;(n+1) )

Grebogi gives a sucient condition on the value of de necessary to estimate the correlation dimension of an attractor, not to avoid all possible self intersections. 4 The standard example is the embedding of motion around a gure 8 in two dimension. At the crossing point in the centre of the gure trajectories cross. However, one can imagine if this was embedded in three dimensions then these trajectories may not intersect. 3

23

2.1. Reconstruction

may or may not still be close. The increase in the distance between these two point is given only by the di erence between the last components NN 2 2 NN 2 kvbt ; vd t k ; kvt ; vt k = (yt;(n+1) ; yt0 ;(n+1) ) :

One will typically calculate the normalised increase to the distance between these two points and determine that two points are false nearest neighbours if

jyt;(n+1) ; yt0;(n+1) j  RT : kvt ; vtNN k

A suitable values of RT depends on the spatial distribution of the embedded data vt . If RT is too small then true near neighbours will be counted as false, if RT is too large then some false near neighbours will not be included. Typically 10  RT  30, the calculations in this thesis all have a value of RT = 15. One must ensure that the chosen value of RT is suitable for the spatial distribution of the data under consideration | this may be done by trialling a variety of values of RT . By determining if the closest neighbour to each point is false one can then calculate the proportion of false nearest neighbours for a given embedding dimension n. We can then choose as the embedding dimension de the minimum value of n for which the proportion of points which satisfy the above condition is below some small threshold. In this thesis we set this threshold to be 1%, however, this value is entirely arbitrary. Typically one could expect the proportion of points satisfying this to gradually decrease as the embedded data is \unfolded" in increasing embedding dimension and eventually plateau at a relatively low level.

2.1.2 Embedding lag  Any value of  is theoretically acceptable, but the shape

of the embedded time series will depend critically on the choice of  and it is wise to select a value of  which separates the data as much as possible. One typically is concerned with the evolution of the dynamics in phase space. By ensuring that the data are maximally spread in phase space the vector eld will be maximally smooth. Spreading the data out minimises possibly sharp changes in direction amoungst the data. From a topological view-point, spreading data maximally makes ne features of phase space (and the underlying attractor) more easily discernible. General studies in nonlinear time series [2] suggest the rst minimum of the mutual information criterion [102, 110], the rst zero of the autocorrelation function [104] or one of several other criteria to choose  . Our experience and numerical experiments suggest that selecting a lag approximately equal to one quarter of the approximate period of the time series produce comparable results to the autocorrelation function but is more expedient. Note that the rst zero of the autocorrelation function will be approximately the same as one quarter of the approximate period if the data are almost periodic. Numerical experiments with these data show that either of these methods produce superior results to the mutual information criterion (MIC). We will consider each of these methods in turn.

24

Chapter 2. Attractor reconstruction from time series

Autocorrelation De ne the sample autocorrelation of a scalar time series yt of N measurements to be

P

PN (T ) = n=1P(yNn+T ; y)(yn2 ; y) n=1 (yn ; y)

where y = N1 Nn=1 yn is the sample mean. The smallest positive value of T for which (T )  0 is often used as embedding lag. For data which exhibits strong periodic component it suggests a value for which the successive coordinates of the embedded data will be virtually uncorrelated whilst still being close (temporally). We stress that a choice of T such that the sample autocorrelation is zero is purely prescriptive. Sample autocorrelation is only an estimate of the autocorrelation of the underlying process, however the sample autocorrelation is sucient for estimating time lag. Mutual information A competing criterion relies on the information theoretic concept of mutual information, the mutual information criterion (MIC). In the context of a scalar time series the information I (T ) can be de ned by

I (T ) =

N X n=1

P (yn ; yn+T ) log2 PP(y(y)nP; y(ny+T ) ) ; n

n+T

where P (yn ; yn+T ) is the probability of observing yn and yn+T , and P (yn ) is the probability of observing yn . I (T ) is the amount of information we have about yn by observing yn+T , and so one sets  to be the rst local minima of I (T ). Approximate period The rationale of these previous two methods is to choose the lag so that the coordinate components of vt are reasonably uncorrelated while still being \close" to one another. When the data exhibit strong periodicity | as is the case with respiratory patterns | a value of  that is one quarter of the length of the average breath generally gives a good embedding. This lag is approximately the same as the time of the rst zero of the autocorrelation function. Coordinates produced by this method are within a few breaths of each other (even in relatively high dimensional embeddings) whilst being spread out as much as possible over a single breath. Moreover, for embedding in three or four dimensions (as will be suggested by false nearest neighbour techniques) the data are spread out over one half to three quarters of a breath. This means that the coordinates of a single point in the three or four dimensional vector time series vt represents most of the information for an entire breath. This choice of lag is extremely easy to calculate and for the data sets that we consider it also seems to give much more reliable results than the mutual information criterion.

2.2 Correlation dimension We are accustomed to thinking of real world objects as one, two or three dimensional. However, there exist complex mathematical objects, called fractals, that have non-integer dimension, a so called fractal dimension. Many real world phenomena, in

25

2.2. Correlation dimension

particular chaotic dynamical systems, can be observed to have properties of a fractal, including a non-integer dimension. A meaningful de nition of fractal dimension comes from a generalisation, or extension, of well known properties of integer dimension objects. Most applications of correlation dimension to physiological sciences have utilised the Grassberger and Procaccia algorithm. However, in this thesis we employ a new algorithm, which is technically more complex, but is in practice more reliable and less prone to misinterpretation. Unlike previous estimation methods this new algorithm recognises that the dimension of an object (its structural complexity) may vary depending on how closely you examine it. Hence the value of the estimate of correlation dimension may change with scale. It therefore o ers a more informative and accurate estimate of dimension. Computing correlation dimension dc as a function of scale dc ("0 ) can tell us much more about the structure of an object, for example, it can indicate the presence of large scale \periodic" motion and simultaneously detect smaller scale, higher dimensional, \chaotic" motion and noise. Quoting a single number as the correlation dimension of a data set ignores much of this information, in many respects it produces an \average dimension". Plots of dimension as a function of scale are particularly important when studying complex physiological behaviour because they yield far more information than a single estimate at a xed scale.

2.2.1 Generalised dimension Once we have embedded the data properly we

wish to measure the complexity of the \cloud" of points vt . The measure we use in this paper is the correlation dimension. We de ne the correlation dimension by generalising the concept of integer dimension to fractal objects with non-integer dimension. In dimensions of one, two, three or more it is easily established, and intuitively obvious, that a measure of volume V (") (e.g. length, area, volume and hyper-volume) varies as

V (") / "d ;

(2.2)

where " is a length scale (e.g. the length of a cube's side or the radius of a sphere) and d is the dimension of the object. For a general fractal it is natural to assume a relation like equation (2.2) holds true, in which case its dimension is given by, d  loglogV "(") : (2.3) Let fvtgNt=1 be an embedding of a time series in Rde . De ne the correlation function, CN ("), by  ;1 N

CN (") = 2

X 0i de) the embedded time series will \ ll" the embedding space. If the time series is of in nite length then the dimension dc of the embedded time series will then be equal to de . If the time series is nite then the dimension dc of the embedded time series will be 4 In

particular statistics based on the correlation integral.

4.2. Correlation dimension as a pivotal test statistic | linear hypotheses

51

less than de 5 . For a moderately small embedding dimension this di erence is typically not great and is dependent on the estimation algorithm and the length of the time series, and independent of the particular realisation. Hence, if the correlation dimension dc of all surrogates consistent with the hypothesis under consideration exceeds de then correlation dimension is a pivotal test statistic for that value of de . An examination of the \pivotalness" of the correlation integral (and therefore correlation dimension) can be found in a recent paper of Takens [149]. Takens' approach is to observe that, if  and 0 are two distance functions in the embedded space X (we consider X = Rn , Takens considers a general compact q -dimensional manifold) and k is some constant and for all x; y 2 X

k;1(x; y )  0(x; y )  k(x; y )

(4.1)

then the correlation integral limN !1 CN (") with respect to either distance function is similarly bounded and hence the correlation dimension with respect to each metric will be the same. This result is independent of the conditions of Takens' embedding theorem (i.e. that n > 2dc + 1 for X = Rn ). Hence if we (for example) embed a stochastic signal in Rn the correlation dimension will have the same value with respect to the two di erent distance functions  and 0. To show that dc is pivotal for the various linear hypotheses addressed by algorithm 0, 1 and 2 it is only necessary to show that various transformations can be applied to a realisation of such processes which have the a ect of producing i.i.d. noise and are equivalent to a bounded change of metric as in (4.1). Our approach is to show that surrogates consistent with each of the three standard linear hypotheses are at most a C 2 function from Gaussian noise N (0; 1). A C 2 function on a bounded set (a bounded attractor or a nite time series) distorts distance only by a bounded factor (as in equation (4.1)) and so the correlation dimension is invariant. We therefore have the following new result.

Proposition 4.1: The correlation dimension dc is a pivotal test statistic for a hypothesis  if 8F1 ; F2 2 F and embeddings 1;2 : R 7;! X1;2 there exists an invertible C 2 function f : X1 7;! X2 such that 8 t f (1 (F1(t))) =

2(F2(t)).

Proof: The proof of this proposition is outlined in the proceeding arguments. Let F1 ; F2 2 F be particular processes consistent with a given

hypothesis and F1 (t) and F2 (t) realisations of those processes. We have that 8 tf (1 (F1(t))) = 2(F2(t)), and so if 1(x1); 1(y1) 2 X1 and 2(x2); 2(y2) 2 X2 are points on the embeddings 1 and 2 of F1 (t) and F2(t) respectively, then f (1(x1)) = 2 (x2) and f (1(y1 )) = 2(y2 ). Let 2 be a distance 5 This

is particularly likely for a short time series and large embedding dimension.

52

Chapter 4. Surrogate analysis

function on X2 , then de ne 1(1(x1 ); 1(y1 )) := 2(f (1(x1 )); f (1(y1))) = 2(2(x2 ); 2(y2 )): Clearly (4.1) is satis ed if 1 is a well de ned distance function. The triangle inequality, the associative property, and non-negativity of 1 are trivial. However, 1(1(x1 ); 1(y1 ) = 0 , 1 (x1) = 1 (y1) requires that f is invertible. Hence, if f is invertible (4.1) is satis ed, lim N !1 CN (") on X1 and X2 are similarly bounded, and therefore the correlation dimension of X1 and X2 are identical.

 Hence, if any particular realisation of a surrogate consistent with a given hypothesis is a C 2 function from i.i.d. noise (which in turn is a C 2 function from Gaussian noise) then correlation dimension is a pivotal statistic for that hypothesis. In the following section we demonstrate dc is a pivotal statistic for each of the linear hypotheses 0, 1 , and 2 .

4.2.1 Linear hypotheses Let us consider the problem of correlation dimension

being pivotal for the linear hypotheses more carefully. First consider the hypothesis  that z  N (0; 1), clearly F is singleton and so dc is a pivotal statistic (in fact any statistic is pivotal). Now let 0 be the hypothesis that z  N (;  2) for some  and some . If F 2 F0 then F ;  2 F , but this is an ane transformation and does not a ect a statistic invariant under di eomorphisms of the embedded data; correlation dimension is such a statistic. In general, if z  D where D is any probability distribution, then the ane transformation F ; should be replaced by a monotonic transformation. Let 1 be the hypothesis that z is linearly ltered noise. In particular let F 2 F1 be ARMA(n; m). That is, F is de ned by

zt = a:fzigtt;;n1 + b:fi gtt;;1m where a 2 Rn , b 2 Rm , fzi gtt;;1n = (zt;1; zt;2 ; : : : ; zt;n ) (and fi gtt;;1m similarly) and   N (0; 1). Again, a suitable linear transformation

zt 7;!

zt ; a:fzigtt;;1n + (b2; b3; : : : ; bm):figtt;;2m = t;1 b1

takes such a time series to Gaussian noise (in general, i.i.d. noise). Similarly if 2 is the hypothesis that z is a monotonic nonlinear transformation of linearly ltered noise, then one only needs to show that the monotonic nonlinear transformation g : R ! R does not a ect the correlation dimension. If g is C 2 , this is a direct consequence of the above arguments. If g is not C 2 then it can be approximated arbitrarily closely by a C 2 function6 . 6 If

this argument does not appear particularly convincing then keep in mind that very few AD convertors (or indeed digital computers) are C 2 , and so, time lag embeddings may never be used with digital observations (either experimental or computational).

4.2. Correlation dimension as a pivotal test statistic | linear hypotheses

53

The above arguments do not guarantee that the correlation dimension dc ("0) estimated by Judd's algorithm will be a pivotal statistic, it only implies that the actual correlation dimension will be. The technical details of Judd's algorithm have been considered elsewhere [60, 61], and an independent evaluation of this algorithm is given by Galka and colleagues [37]. Provided one chooses a suitably small scale "0 the statistic dc ("0 ) will be (asymptotically) pivotal. The above argument, in conjunction with technical results concerning Judd's algorithm [37, 60, 61], imply that correlation dimension estimated by this algorithm is pivotal and the estimates are consistent.

4.2.2 Calculations Estimates of the probability density of correlation dimension

for various linear surrogates are shown in gures 4.1, 4.2 and 4.4. Figures 4.1 and 4.2 compare the estimates of pT;F (t) for various classes of simple and composite hypotheses concerned with algorithm 1 ( gure 4.1) and 2 ( gure 4.2). Figure 4.4 compares di erent constrained and non-constrained realisation techniques for the experimental data of gure 4.3. In each case the probability density of correlation dimension pdc ("0 );F (t) was estimated for xed values of "0 by linearly interpolating the individual correlation dimension estimates to get an ensemble of values of dc ("0 ) from which pdc ("0 );F (t) is estimated following methods described by [127]. The ensemble of probability density estimates were then used to calculate the contour plots of pdc ("0 );F (t) for all values of "0 for which our correlation dimension estimation algorithms converged. Figures 4.1 and 4.2 show that the probability density of correlation dimension is independent of which particular form of linear ltering one applies. In both gure 4.1 and gure 4.2, the rst panel shows an estimate of the probability density function (p.d.f.) of correlation dimension for realisations given a particular (in gure 4.2, monotonic nonlinearly ltered) autoregressive process; the second panel shows an estimate of the p.d.f. from surrogates of one of the realisations in the rst panel. The third and fourth panels show estimates of the p.d.f. of correlation dimension for realisations of di erent (stable) autoregressive processes. The probability density plot for AAFT (algorithm 2) surrogates is virtually identical to that for di erent realisations of a single process, and for random processes. This agreement is particularly strong between the rst two panels of each gure (distinct realisations of one process and surrogates of a single realisation). The slightly greater variation with the third and fourth panels is most probably a result of the scaling properties of our estimates of correlation dimension. However, this only produces convergence of the correlation dimension estimates at di erent scales "0 , not distinct probability distributions. The plots only fail to agree for values of "0 for which an estimate of dc ("0) was not obtained. The panels in gure 4.1 show precise agreement for the range ;2 < log("0 ) < ;1:8, in gure 4.2 the range is ;5 < log("0) < ;3:7. Outside these ranges one or more of the panels correspond to surrogates that failed to produce convergence of the correlation dimension algorithm at that particular scale.

54

Chapter 4. Surrogate analysis

(ii)

5

correlation dimension

correlation dimension

(i)

4.5

4 −2.4

−2.2 −2 log(epsilon0)

5

4.5

4

−1.8

−2.4

5

4.5

4 −2.4

−2.2 −2 log(epsilon0)

−1.8

(iv) correlation dimension

correlation dimension

(iii)

−2.2 −2 log(epsilon0)

−1.8

5

4.5

4 −2.4

−2.2 −2 log(epsilon0)

−1.8

Figure 4.1: Probability distribution for correlation dimension estimates of AR(2) processes: Shown are contour plots which represent the probability density of correlation dimension estimate for various values of "0 . Figure (i) is the probability distribution function (p.d.f.) for various realisations of the AR(2) process xn ; 0:4xn;1 + 0:7xn;2 = n , n  N (0; 1), gure (ii) shows the p.d.f. for AAFT surrogates of one of these processes. Figure (iii) and (iv) are for random (stable) AR(2) processes. In each of these two calculations 1 and 2 were selected uniformly (subject to j1 j; j2j < 1) and the autoregressive process is xn +(1 + 2 )xn;1 + 1 2 xn;2 = n , n  N (0; 1) (see [104]). In the third plot 1 ; 2 2 R, in the fourth 1 ; 2 2 C. For each calculation 50 realisations of 4000 points were calculated, and their correlation dimension calculated for embedding dimension de = 3; 4; 5; 10; 15 (shown are the results for de = 5) using a 10000 bin histogram to estimate the density of inter-point distances, the other calculations produced similar results. Note, for some values of "0 (particularly in (iii)) our dimension estimation algorithm did not provide a value for dc ("0). This does not indicate that the estimate of the probability density of correlation dimension are distinct, only that we were unable to estimate correlation dimension. In each case our calculations show a very good agreement between the p.d.f. of dc ("0 ) for all values of "0 for which a reliable estimate could be obtained.

55

4.2. Correlation dimension as a pivotal test statistic | linear hypotheses

(ii) correlation dimension

correlation dimension

(i) 2.4 2.2 2 1.8 1.6 1.4

−5

−4.5 −4 log(epsilon0)

2.4 2.2 2 1.8 1.6 1.4

−3.5

−5

2.4 2.2 2 1.8 1.6 1.4

−5

−4.5 −4 log(epsilon0)

−3.5

(iv) correlation dimension

correlation dimension

(iii)

−4.5 −4 log(epsilon0)

−3.5

2.4 2.2 2 1.8 1.6 1.4

−5

−4.5 −4 log(epsilon0)

−3.5

Figure 4.2: Probability density for correlation dimension estimates of a monotonic nonlinear transformation of AR(2) processes: Shown are contour plots which represent the probability density of correlation dimension estimate for various values of "0 . Similar to gure 4.1, the four plots are of the p.d.f. of dc ("0 ) for: (i) various realisations of the AR(2) process xn ; 0:4xn;1 + 0:7xn;2 = n , n  N (0; 1), observed by g (x) = x3 ; (ii) AAFT surrogates of one of these processes; (iii) random (stable) AR(2) processes observed by g (x) = x3 ; (iv) random (stable, pseudoperiodic) AR(2) process observed by g (x) = x3 . For these last two calculations 1 and 2 were selected uniformly (subject to j1j; j2j < 1) and the autoregressive process is xn + (1 + 2 )xn;1 + 1 2 xn;2 = n , n  N (0; 1). In (iii) 1 ; 2 2 R, in (iv) 1 ; 2 2 C. In each calculation 50 realisations of 4000 points were calculated, and their correlation dimension calculated for de = 3; 4; 5; 10; 15 (shown are the results for de = 5, the other calculations produced similar results) using a 10000 bin histogram to estimate the distribution of inter-point distances. In each case our calculations show a very good agreement between the p.d.f. of dc ("0 ) for all values of "0 for which a reliable estimate could be obtained. Similar results were also obtained using g (x) = sign(x)jxj1=4 as an observation function.

56

Chapter 4. Surrogate analysis

(a) Abdominal movement 2 1 0 −1 −2 0

500

1000

1500

2000

2500

3000

3500

4000

3000

3500

4000

(b) Electrocardiogram 4 2 0 −2 −4 −6 0

500

1000

1500

2000

2500

Figure 4.3: Experimental data: The abdominal rib movement and electrocardiogram signal for an 8 month old male child in rapid eye movement (REM) sleep. The 4000 data points were sampled at 50Hz, and digitised using a 12 bit analogue to digital convertor during a sleep study at Princess Margaret Hospital for Children, Subiaco, Western Australia. These data are from group A (section 1.2.2).

57

4.2. Correlation dimension as a pivotal test statistic | linear hypotheses a (i)

b (i) correlation dimension

correlation dimension

5 4.5 4 3.5 3

−2

−1.8 −1.6 log(epsilon0) a (ii)

correlation dimension

correlation dimension

4 3.5

4.1 4 3.9

−2.2

−2

−1.8 log(epsilon0) b (ii)

−1.6

−2.2

−2

−1.8 log(epsilon0) b (iii)

−1.6

−2.2

−2

−1.8 log(epsilon0)

−1.6

4.4 4.3 4.2 4.1 4 3.9 3.8

−2.2

−2

−1.8 −1.6 log(epsilon0) a (iii)

−1.4

correlation dimension

5 correlation dimension

4.2

−1.4

4.5

4.5 4 3.5 3

4.3

3.8 −2.2

5

3

4.4

4.4 4.3 4.2 4.1 4 3.9 3.8

−2.2

−2

−1.8 −1.6 log(epsilon0)

−1.4

Figure 4.4: Probability density for correlation dimension estimates for surrogates of experimental data: Shown are contour plots which represent the probability density of correlation dimension estimate for various values of "0 . The rst three panels are p.d.f. estimates for surrogates of the abdominal movement data in gure 4.3 generated by: a.(i) a non-constrained realisation technique (we rescaled the data to be normally distributed, estimated the minimum description length best autoregressive model of order less that 100 using the techniques of [62], generated random realisations of that process driven by Gaussian noise, and rescaled these to have the same rank distribution as the data); a.(ii) AAFT surrogates; and a.(iii) surrogates generated using the method described by Schreiber and Schmitz [121]. The last three plots are similar calculations for the electrocardiogram data from gure 4.3 generated by: b.(i) the non-constrained realisation technique; b.(ii) AAFT surrogates; and b.(iii) surrogates generated using the method described by Schreiber and Schmitz. In each calculation 50 realisations of 4000 points were calculated, and their correlation dimension calculated of de = 3; 4; 5 (shown are the results for de = 5, the other calculations produced similar results) using a 10000 bin histogram to estimate the distribution of inter-point distances. In each case our calculations show a very good agreement between the p.d.f. of dc ("0 ) for all values of "0 for which a reliable estimate could be obtained.

58

Chapter 4. Surrogate analysis

There is substantial di erence between the probability densities shown in gure 4.1 and those for gure 4.2. The di erence results from the di erent observation function g (x) = x3 in gure 4.27. This indicates a di erence in the results of the dimension estimation algorithm, the nonlinear transformation g has changed the scale of structure present in the original process, and so yields di erent values of dc ("0). This indicates that correlation dimension is not pivotal over F2 , however, provided one can make a reasonable estimate of the process F 2 F2 which generated z then T is pivotal for the restricted class F~2 where F 2 F~2  F2 8 . Note that the range of values of ; log "0 shown in gures 4.1 and 4.2 are quite distinct, the correlation dimension algorithm does not produce di erent probability density functions, it has only failed to produce an estimate at some scales. Figure 4.4 gives a comparison of the probability distribution for two di erent data sets with various di erent surrogate generation methods. In each column the rst panel shows results for a non-constrained surrogate generation method (we estimated the parameters of the best autoregressive model and generated simulations from it, see the caption of gure 4.4), and constrained surrogate methods suggested by Theiler (panel ii) and Schreiber and Schmitz (panel iii). The surrogates generated by either simple parameter estimation methods, the AAFT method or the method suggested by Schreiber and Schmitz9 produced almost identical results. Hence in this example any surrogate generation method will serve equally well, provided the surrogates are not completely di erent from the data. This con rms our earlier arguments and calculations with stochastic processes.

4.2.3 Results The close agreement between the probability density estimates in

the rst two panels of each of gures 4.1 and 4.2 and panels a.(i)-(iii) and b.(i)-(iii) in gure 4.4 indicate that the surrogate generation methods suggested by Theiler [152] and those of Schreiber and Schmitz [121] generate surrogates for which dc ("0 ) is pivotal. This should be the case as these are all constrained realisation techniques (with the possible exception of algorithm 2 surrogates [121]). The agreement between all four panels in gure 4.1 (and similarly between all four panels in gure 4.2) indicate that dc ("0) is virtually pivotal when  is the hypothesis that the data are linearly ltered noise or a particular monotonic nonlinear transformation of linearly ltered noise. There are minor di erences between the various panels in each gure, but these are only a result of the estimate of dc ("0 ) not converging. 7 We also repeated the calculations of gure 4.2 with g(x) = sign(x)jxj1=4 (note that this not C 2 ) and obtained another set of similar results. All the individual probability density

function is plots were

the same, but they were di erent from those in gures 4.1 and 4.2. 8 One would expect that the nonlinear transformation g would be fairly similar for all F 2 F ~ . 2 From our calculations it appears sucient to ensure that the data and surrogates have identical rank distributions. 9 We iterated the algorithm described in [121] 1000 times to generate each surrogate.

4.3. Correlation dimension as a pivotal test statistic | nonlinear hypothesis

59

The di erence between the results of gure 4.1 and those of gure 4.2 indicate that our estimate of correlation dimension is not pivotal for the hypotheses that the data are any monotonic nonlinear transformation of linearly ltered noise. The scale dependent properties of dc ("0 ) have altered the value of this statistic for various observation functions g . The linear models built to estimate pdc ("0 );F produced estimates of correlation dimension which closely agreed with those from the constrained surrogate generation methods. This indicates that a non-constrained realisation technique can do as well as a constrained one. Correlation dimension estimates dc ("0) are not pivotal for the set of all processes consistent with the hypothesis that the data are a monotonic nonlinear transformation of linearly ltered noise (otherwise all the probability density estimate in gures 4.1, 4.2, and 4.4 would be identical). However, the p.d.f. of dc ("0 ) for various realisations are similar enough to allow for the use of some more general non-constrained surrogate generation methods (such as the parametric model estimation we employ in gure 4.4 panel a.(i) and b.(i), and possibly the method suggested in [149]). Furthermore the p.d.f. of dc values for the surrogate generation methods of Schreiber and Schmitz [121] and Theiler [152] are identical. The di erence in the results between gures 4.1, 4.2, and 4.4 is most likely a result of the di erent choice of observation function g a ecting the scaling properties of the correlation dimension estimate. By ensuring the rank distribution of the data and surrogate are the same (as in gure 4.4, panels a.(i) and b.(i)) one can generate surrogates for which dc is pivotal. Alternatively one could choose a statistic without such sensitive scale dependence. However, for nonlinear hypothesis testing the author believes that sensitivity to scaling properties is an important feature of this particular test statistic.

4.3 Correlation dimension as a pivotal test statistic | nonlinear hypothesis Beyond applying these linear hypotheses one may wish to ask more speci c questions; are the data consistent with (for example) a noise driven periodic orbit? In particular, a hypothesis similar to this is treated by Theiler's cycle shued surrogates (section 3.3), we apply this method in sections 8.2.3 and 8.3.3. In this section we focus on more general hypotheses. An experimental application of these methods has been presented elsewhere and will appear latter in this thesis. In chapter 8 we test the hypothesis that infant respiration during quiet sleep is distinct from a noise driven (or chaotic) quasi-periodic, toroidal, or ribbon attractor (with more than two identi able periods). Such an apparently abstract hypothesis can have real value, these results have been con rmed with observations of cyclic amplitude modulation in the breathing of sleeping infants [133, 140] (chapters 8 and 9) during quiet sleep and in the resting respiration of adults at high altitude [160].

60

Chapter 4. Surrogate analysis

To apply such complex hypotheses we build cylindrical basis models using a minimum description length criterion (see section 2.3 and chapter 6) and generate noise driven simulations (surrogate data sets) from these models. This modelling scheme has been successful in modelling a wide variety of nonlinear phenomena. However, it involves a stochastic search algorithm. This method of surrogate generation does not produce surrogates that can be used with a constrained realisation scheme10 , and so a pivotal statistic is needed.

4.3.1 Nonlinear hypotheses It is important to determine if the data are gen-

erated by a process consistent with a speci c model or a general class of models. To do this we need to determine exactly how representative a particular model is for a given test statistic | how big is the set F for which T is pivotal? By comparing a data set and surrogates generated by a speci c model, are we just testing the hypothesis that a process consistent with this speci c model generated the data or can we infer a broader class of models? In either case (unlike constrained realisation linear surrogates), it is likely that the hypothesis being tested will be determined by the results of the modelling procedure and therefore depend on the particular data set one has. Many of the arguments of section 4.2 apply here as well; the hypothesis one can test will be as broad as the class of all systems with distance function bounded by equation (4.1) (in the case of correlation integral based test statistics). In particular proposition 4.1 holds | an invertible C 2 function will yield only a bounded change in the correlation integral. Consider the other side of the problem. We want T to be a pivotal test statistic for the hypothesis , where  is a broad class of nonlinear dynamical processes. For example, if F is the set of all noise driven processes then dc ("0) will not be pivotal. However, if we are able to restrict ourselves to F~  F where T is pivotal on F~ then the problem is resolved. To do this we simply rephrase the hypothesis to be that the data are generated by a noise driven nonlinear function (modelled by a cylindrical basis model) of dimension d. For example, this would allow one to test if the data are consistent with a periodic orbit with 2 degrees of freedom driven by Gaussian noise. Furthermore, the scale dependent properties of our estimate of dc ("0) provide some sensitivity to the size (relative to the size of the data) of structures of a particular dimension. This is a much more useful hypothesis than that the process is noisy and nonlinear | if this was our hypothesis, then what would be the alternative? Because of the complexity of our dimension estimation algorithm and the class of nonlinear models it is necessary to compare calculations of the probability density of the test statistic for various models. Having done so one cannot make any general claims about the \pivotalness" of a given statistic. However, for a given data set it is possible to compare the probability distributions of a test statistic for various classes of nonlinear models 10 If we are unable

to estimate the model parameters consistently (from a single data set) then we are certainly not going to be able to produce a surrogate which yields the same estimates of parameters as the data.

4.3. Correlation dimension as a pivotal test statistic | nonlinear hypothesis

61

Abdominal movement 4 3 2 1 0 −1 −2 0

200

400

600

800

1000

1200

1400

1600

Figure 4.5: Experimental data: The abdominal rib movement for an 2 month old female child in quiet (stage 3{4) sleep. The 1600 data points were sampled at 12.5Hz (to ease the computational load involved in building the cylindrical basis model this has been reduced from 50Hz), and digitised using a 12 bit analogue to digital convertor during a sleep study at Princess Margaret Hospital for Children, Subiaco, Western Australia. These data are from group A (section 1.2.2) and is the same data set as illustrated in gure 6.1. and depending on the \pivotalness" of the statistics determine the hypothesis being tested.

4.3.2 Calculations Figure 4.6 presents some experimental results from the data

of gure 4.5. We have estimated the probability density for an ensemble of models and for particular models from an experimental data set. We employ a di erent data set here for illustration purposes11 these data are far more non-stationary than that in gure 4.3, and proves to be a greater modelling challenge. These calculations con rm that the distribution of correlation dimension estimates for di erent realisation of one model are the same as for di erent realisations of many models. The models used in this calculation were selected to have simulations with asymptotically stable periodic orbits. Models of this data set produce simulations with either asymptotic stable periodic orbits or xed points (the second behaviour is clearly an inappropriate model of respiration). The p.d.f. of dc for all models therefore exhibits two modes. We are only concerned with a unimodal distribution at any one time. Figure 4.6 (ii), (iii) and (iv) show the probability density for particular models selected from the ensemble of models used in (i). Panel (iii) is the result of the calculations for the model which gave the smallest estimate of dc ("0) for log("0) = 1:8 in (i), that is 11 These

calculations have also been repeated with the data in gure 4.3 and equivalent conclusions were reached.

62

Chapter 4. Surrogate analysis

(ii) correlation dimension

correlation dimension

(i) 2.6 2.4 2.2 2 1.8 1.6 −3

−2.5 −2 log(epsilon0)

2.6 2.4 2.2 2 1.8 1.6

−1.5

−3

2.6 2.4 2.2 2 1.8 1.6 −3

−2.5 −2 log(epsilon0)

−1.5

(iv) correlation dimension

correlation dimension

(iii)

−2.5 −2 log(epsilon0)

−1.5

2.6 2.4 2.2 2 1.8 1.6 −3

−2.5 −2 log(epsilon0)

−1.5

Figure 4.6: Probability density for correlation dimension estimates for nonlinear surrogates of experimental data: Shown are contour plots which represent the probability density of correlation dimension estimate for various values of "0 . The data used in this calculation is illustrated in gure 4.5. The gures are p.d.f. estimates for surrogates generated from: (i) realisations of distinct models; (ii) realisations for one of the models used in (i) with approximately the median value of correlation dimension (dc ("0 ) for log "0 = ;1:8); (iii) realisations for the model used in (i) with the minimum value of correlation dimension; (iv) realisations for the model used in (i) with the maximum value of correlation dimension. In each calculation 50 realisations of 4000 points were calculated, and their correlation dimension calculated of de = 3; 4; 5 (shown are the results for de = 5, the other calculations produced equivalent results) using a 10000 bin histogram to estimate the distribution of inter-point distances. In each case our calculations show a very good agreement between the p.d.f. of dc ("0) for all values of "0 for which a reliable estimate could be obtained.

63

4.4. Conclusion

the model that generated the simulation with the lowest dimension. Panel (iv) is the result of the calculations for the model which gave the highest dimension estimate in (i). Panel (ii) corresponds to the median dimension estimate in (i). Despite this, all these probability densities are very nearly the same; there is no low bias in (iii) and no high bias in (iv). This indicates that dc ("0) is (asymptotically) pivotal, simulations from any (periodic) model of the data will produce the same estimate of the probability distribution of dc ("0 ). Hence one may build a single model of the data, estimate the distribution of dc ("0 ), and use that distribution to test the hypothesis that the data was generated by a process of the same general form as the model (this is the procedure followed in chapter 8).

4.3.3 Results The preceding calculations indicate that parametric nonlinear

models of the data can be used to produce a pivotal class of functions when using correlation dimension as the statistic. That is, estimating the distribution of correlation dimension estimates for di erent models of a single set of (infant respiratory) data is equivalent to estimating the distribution of distinct realisation of a single model. Models which produced low (or high) correlation dimension estimates in gure 4.6 (i) did not produce estimates with lower or higher values of correlation dimension any more often than a more typical model. Indeed, they generated estimates with the same distribution of values. In general one may, build nonlinear models of a data set and generate many noise driven simulation from each of these models and compare the distributions of a test statistic for each model and for broader groups of models (based on qualitative features, such as xed points or periodic orbits, of these models). By comparing the value of the test statistic for the data to each of these distribution (for groups of models) one may either accept or reject the hypothesis that the data was generated by a process with the same qualitative features as the models used to generate a given p.d.f.

4.4 Conclusion We have suggested an extension of surrogate generation techniques to nonlinear parametric modelling. By applying traditional surrogate tests as well as building nonlinear models one has a powerful aid to classifying the hypothesised generic dynamics underlying a time series. When extending the linear non-parametric surrogate tests suggested previously to the case of nonlinear parametric modelling it is necessary to ensure that the test statistic employed is suitably pivotal. Dynamic measures such as correlation dimension ensure \pivotalness" provided the hypothesis is restricted to a particular class of dynamical system. However one must be able to estimate these quantities reliably . We have argued that any dynamic measure is a pivotal statistic for a very wide range of standard (linear) and nonlinear hypotheses addressed by surrogate data anal-

64

Chapter 4. Surrogate analysis

ysis. However, one must be able to estimate this quantity consistently from data. We have at our disposal a very powerful and useful method of estimating correlation dimension dc ("0) as a function of scale "0 . The details of this method have been considered elsewhere [60, 61] and an examination of the accuracy of this method may be found in, for example, [37]. Some scaling properties of this estimate prevent it from being pivotal over as wide a range of di erent process as the true correlation dimension if it could be calculated12 . However, this statistic is still pivotal for a large enough class of processes to be an e ectively pivotal test statistic for surrogate analysis. Rescaling the surrogates to have the same rank distribution as the data produced suciently good results for the linear surrogates in section 4.2. Estimates of dc ("0 ) are pivotal over the sets of surrogates produced by algorithm 0, 1 and 2, and over the class of nonlinear surrogates generated by simulations of cylindrical basis models. This gives us a quick, e ective and informative method for testing the hypotheses suggested by algorithm 0, 1, and 2 surrogates. Furthermore, it relieves the concerns raised by Schreiber and Schmitz [121]. If the test statistic is (asymptotically) pivotal it doesn't matter if the power spectrum of surrogate and data are not identical (this is only a requirement of a constrained realisation scheme). The correlation dimension estimates of a monotonic nonlinear transformation of linearly ltered noise will have the same probability distribution regardless of exactly what the power spectrum is. With the help of minimum description length pseudo-linear modelling techniques (section 2.3) correlation dimension also provides a useful statistic to test membership of particular classes of nonlinear dynamical processes. The hypothesis being tested is in uenced by the results of the modelling procedure and cannot be determined a priori. After checking that all models have the same distribution of test statistic values and are representative of the data (in the sense that the models produce simulations that have qualitative features of the data), one is able to build a single nonlinear model of the data and test the hypothesis that the data was generated from a process in the class of dynamical processes that share the characteristics (such as periodic structure) of that model. In many cases the models described in section 2.3 are not suciently similar to respiratory data. Chapter 5 described selection of embedding parameters and chapter 6 introduce some new improvements to this modelling procedures to produce superior results. Chapters 7, 8, and 10 discuss applications of this improved modelling algorithm. 12 The

author believes that this may be a useful feature of this version of correlation dimension. The scale dependent properties of this algorithm mean that the algorithm may be able to di erentiate between systems with identical correlation dimension. For example, rescaling the data with an instantaneous nonlinear transformation will produce a di erent estimate of dc ("0 ) (at least for large "0 ) but not change the actual (asymptotic, "0 ! 0) value of dc . This would allow one to di erentiate between (for example) di erent shaped 2 dimensional periodic orbits.

CHAPTER 5

Embedding | Optimal values for respiratory data Before we describe the application of radial basis modelling to infant respiration and the new modelling algorithm we use, it is necessary to consider some further aspects of embedding and delay reconstruction. In chapter 2 we introduced a general time delay embedding and discussed some features of these embeddings. In particularly, we introduced several methods to estimate the parameters  and de of the time delay embedding. In this chapter we will brie y describe the techniques utilised in this thesis to estimate the embedding parameters. First we will expand on several alternative embedding strategies. In section 5.2 we discuss the estimation of embedding dimension and in section 5.3 we discuss the choice of embedding lag.

5.1 Embedding strategies The usual time delay embedding was described in chapter 2. However, in this thesis we will generalise this further, and to do so we need to introduce some additional terminology.

De nition 5.1: An embedding of the form (yt; yt; ; yt;2 ; : : : ; yt;(d;1) ) we call a d dimensional uniform embedding with lag  .

This is the usual time delay embedding. We call this a uniform embedding in anticipation of the following de nitions. De nition 5.2: A nonuniform embedding is one of the form (yt;`1 ; yt;`2 ; yt;`3 ; : : : ; yt;`d ) where `i < `j for all i < j . This is an obvious extension of a uniform embedding. Nonuniform embeddings are of particular use when the time series has several di erent time scales of dynamics or several fundamental cycle lengths. For example, the often cited sunspot data have been found to be best modelled with an embedding of the form yt+1 = f (yt ; yt;1 ; yt;8) [64, 62]. De nition 5.3: A variable embedding strategy is one for which the embedding is di erent for di erent parts of phase space. This de nition is somewhat ambiguous, general variable embeddings will be discussed more in chapter 6 Variable embedding strategies are useful for data that represents a model with more detail in some parts of phase space than in others. For example the Lorenz attractor [65] is mostly two dimensional, except for the central more complicated region. A comprehensive discussion of the nature of these di erent embeddings may be found in [64].

65

66

Chapter 5. Embedding | Optimal values for respiratory data 0.8

proportion of false nearest neighbors

0.7

0.6

0.5

0.4

0.3

0.2

0.1

0 0

5

10

15

embedding dimension

Figure 5.1: False nearest neighbours: False nearest neighbour calculation for the data illustrated in gure 6.1 (1600 points sampled at 12:5 Hz) embedded with a time delay embedding,  = 5. (RT = 15). The location and level of the plateau illustrated in this gure is typical for our infant respiratory data.

5.2 Calculation of de Numerical experiments indicate that four dimensions are sucient to remove false nearest neighbours (see section 2.1.1) from the data, see gure 5.1. Furthermore, it is at approximately this embedding dimension that the correlation dimension estimates appear to plateau. Taken's sucient condition on successful reconstruction of the attractor by embedding requires the de > 2dc + 1 where dc is the correlation dimension of the attractor. For our data, with 3 < dc  4 (see chapter 8), this would suggest that d > 8 is necessary. However, embedding in this dimension o ers no improvement to the modelling process and our false nearest neighbour calculations indicate a much smaller value of d is sucient. For our calculations of correlation dimension we use a wide range of embedding dimension from 2 to 9 (chapter 8). This range covers both the value suggested by our calculations of false nearest neighbours and also the sucient conditions of Takens'

67

5.3. Calculation of 

embedding theorem. For building nonlinear models (chapter 6) we use a variety of di erent embedding strategies. In the case of a uniform embedding we embedded in at least 4 dimensions, the variable embeddings we utilise in chapter 6 embed in a much higher dimension1 dimensions | satisfying the sucient conditions of Takens' theorem.

5.3 Calculation of  In this section we discuss selection of embedding lag  for uniform embeddings. We compare the various methods of calculating this parameter (described in section 2.1.2) and consider some detail of two dimensional embeddings.

5.3.1 Representative values of  There are two main methods [107] for choos-

ing an appropriate value of the lag  ; the rst zero of the autocorrelation function [5, 6] and the rst minimum of the mutual information [2, 36, 82]. The rationale of both of them, however, is to choose the lag so that the coordinate components of vt are reasonably uncorrelated while still being \close" to one another. Table 5.1 gives examples of representative values of lags calculated by each of these methods. When the data exhibits strong periodicity a value of  that is one quarter of the period generally gives a good embedding. This lag is approximately the same as the time of the rst zero of the autocorrelation function. This choice of lag is extremely easy to calculate and for the data sets that we consider it also seems to give much more reliable results than the mutual information criterion.

5.3.2 Two dimensional embeddings An earlier study of respiratory data [24]

suggested a characteristic di erence in the embedding pattern produced by di erent recordings. When embedded in 2 dimensions with a lag calculated as one quarter of the approximate period some recordings had an approximately square shape whilst others had, in general a triangular appearance. Figure 5.2 gives an example of these two shapes. However, this feature is due primarily to the choice of  and is also avoided by viewing the embedding in at least 3 dimensions. This a ect can also be associated with data that remain relatively constant (usually on expiration) for a long period of time. In either case, the embeddings shown in gure 5.2 panel (a) and (b) appear to be di eomorphic. In this section we brie y present a new analysis of this phenomenon to show the reason for the apparent distinction between the embedded shape in gure 5.2 (a) and (b). Let r be the fraction of the total time spent on the expiratory phase of respiration, and for simplicity let us assume a saw tooth wave form, as in gure 5.3. The generalisation to general respiratory wave forms is trivial and obvious. Let  be the embedding lag. The shape of the embedding will now depend only on the relative values of  and . In general we consider four separate cases: (i)  < r; 1 ; r; (ii) 1 ; r <  < r; (iii) 1 This

method builds a model of the form xt+1 = f (xt; xt;1 ; xt;2 ; : : : ; xt;de  ;1 ) and is therefore, (globally) an embedding in Rde  where  is the embedding lag.

68

Chapter 5. Embedding | Optimal values for respiratory data

subject subject 1 (male)

subject 2 (female)

trial respiratory sleep rate state 1 2 3 4 5 6 7 1 2 3 4 5 6 7 8 9

(bpm)

45 35.5 35.5 36 38 38 45.5 18.5 18.5 17 16 16.5 16 18 19 20.5

1{2 3 2{3 3 3{4 2 3 4 4 3 3 4 4 2{3 2{3 3

1 4

calculated value of  (approximate period) MIC 1st zero of 15 18 18 19 19 17 15 41 41 45 45 43 44 39 39 34

21 23 40 24 26 25 21 55 49 57 56 21 48 44 47 48

autocorrelation

20 20 32 21 20 102 17 48 39 1179 49 41 42 42 36 39

Table 5.1: Calculation of  : Sample values of 41 (approximate period), the rst zero of the autocorrelation function and the rst minimum of the mutual information (MIC). Also shown is the sex, sleep state, and respiratory rate (in breaths per minute) for each recording. All data sets are sampled at 50Hz. For the modelling purposes we will discuss later this is grossly oversampled and for those applications we down sample the data to approximately 20 points per period. Note that for most data sets the values of  suggested by all three methods are approximately the same. The 14 (approximate period) is almost always less than then others. The rst zero of the autocorrelation is occasionally much larger than the other two values, this is due to non stationarity in the data destroying the correlated/uncorrelated cycle one expects in the autocorrelation curve of a approximately periodic time series. Generally 14 (approximate period) is less than the rst zero of autocorrelation which is less than the rst minimum of the MIC. Although the MIC gives reliable, consistent, estimates the calculation of mutual information is far more computational intensive than either of the other two methods. These calculations are for data from group D, results for groups A, B, and C are similar (section 1.2.2).

69

5.3. Calculation of 

(a)

(b)

6

6 4

5.5

2 0

5 −2 −4

4.5

−6 4 4

4.5

5

5.5

−8 −10

6

−5

0

5

10

(c) 6

x3

5.5 5 4.5 4 4 5 6 x1

5

4.5

5.5

x2

Figure 5.2: E ect of  on the shape of an embedding: Panel (a) and (b) are two dimensional embeddings of di erent data sets, panel (c) is a (projection of a) three dimensional embedding of the data of panel (a). The data (and choice of embedding lag) for panel (a) and (c) are the same, panel (b) is a di erent data set with a di erent value of embedding lag. Note the distinctive shape of (a) and (b). However, this is due primarily to the choice of  (relative to r, see gure 5.3 and shape of inspiratory/expiratory cycle.

70

Chapter 5. Embedding | Optimal values for respiratory data

6

5

4 0

100

200

300

400

500

600

700

800

900

1000

1

r 1-r

Figure 5.3: Parameter r: The parameter r is the fraction of the total time spent on the expiratory phase of respiration. The data shown in the top panel is far from the saw tooth waveform we approximate it by. This is the most extreme situation, and will e ectively add an extra phase to the dynamics of the embedded data | a section of phase space with slow moving dynamics as all coordinates have similar values.

71

5.3. Calculation of 

(i)

(ii) D C

C y

y t- τ

t- τ

D

A B

B yt

A

yt

(iii)

(iv) A

B

C

B

y

D

y

t- τ

C

t- τ

A D

yt

yt

Figure 5.4: Dependence of shape of embedding on  and r: Panel (i), (ii), (iii), and (iv) represent the four situations described in the text. Each section is denoted (consistent with the text) by A, B, C, and D. Note that, for increasing values of  (relative to r) the embedding produces a self intersection when 1 ; r <  < r or r <  < 1;r. Note that in panel (ii) and (iii) the simple periodic motion is not embedded satisfactorily in R2 | one has self intersections which a 3 dimensional embedding would be required to remove (for those values of  ).

72

Chapter 5. Embedding | Optimal values for respiratory data

r <  < 1 ; r; and (iv) r; 1 ; r <  . In normal respiration we have that r > 1 ; r and increasing  will cause a transition from (i) to (ii) to (iv). We will now describe each of

these four situations, gure 5.4 illustrates these results.

(i.)  < r; 1 ; r. The two dimensional embedding will have four separate sections, where A: both the coordinates yt and yt; are on the expiratory phase of the respiratory cycle. B: yt is on the inspiratory phase and yt; is on the preceding expiratory phase. C: both yt and yt; are on the inspiratory phase. D: yt is on the expiratory phase and yt; is on the preceding inspiratory phase. (ii.) 1 ; r <  < r. The two dimensional embedding will have four separate sections, namely A: both the coordinates yt and yt; are on the inspiratory phase of the respiratory cycle. B: yt is on the expiratory phase and yt; is on the preceding inspiratory phase. C: yt is on a new inspiratory phase whilst yt; is on the preceding inspiratory phase. D: yt is on the inspiratory phase and yt; is on the preceding expiratory phase. (iii.) r <  < 1 ; r. The two dimensional embedding will have four separate sections, namely A: both the coordinates yt and yt; are on the expiratory phase of the respiratory cycle. B: yt is on the inspiratory phase and yt; is on the preceding expiratory phase. C: yt is on a new expiratory phase whilst yt; is on the preceding expiratory phase. D: yt is on the expiratory phase and yt; is on the preceding inspiratory phase. (iv.) 1 ; r; r <  . In this case the four sections are A: B: C:

yt is on the expiratory phase and yt; is on the preceding inspiratory phase. yt and yt; are on successive inspiratory phases. yt is on the new inspiratory phase and yt; is on the preceding expiratory

phase. D: yt and yt; are on successive expiratory phases.

5.3. Calculation of 

73

Hence the embedding will generally have a rectangular appearance. However if 1 ; r <  < r or r <  < 1 ; r the embedded data will (in 2 dimensions) have crossings of trajectories. In general one expects that r  1 ; r and so if  is one quarter of a period ( = 0:25) this situation is avoided and one has an acceptable embedding. However, if r  41 or 1 ; r  41 then the embedding will be either be triangular (the case when r = 14 or 1 ; r = 14 ) or have self intersections. Hence, when choosing an embedding we should select  = 41 (approximate period) and ensure that  < min(r; 1 ; r).

74

Chapter 5. Embedding | Optimal values for respiratory data

CHAPTER 6

Nonlinear modelling This chapter describes an attempt to accurately model the respiratory patterns of human infants using new nonlinear modelling techniques. In chapters 2 and 5 we discussed methods to reconstruct the attractor of a time series from data. Chapters 3 and 4 describe methods one may employ to deduce nonlinear determinism in experimental data. In this chapter we describe necessary modi cations to the modelling algorithm described in section 2.3 and [62] to accurately model the nonlinear dynamics of the human respiratory system. We have evidence to suggest the presence of nonlinearity in the respiration of sleeping infants [136, 140]1 . To produce adequate nonlinear models we found that present methods (section 2.3) have to be improved substantially. This chapter describes the author's improvements to the existing algorithm. We have identi ed periodic uctuation in regular breathing pattern of sleeping infants using linear modelling techniques [133] (see chapter 9). An accurate, reliable and replicable method of building nonlinear models may further aid the identi cation of such subtle periodicities and give some insight into the mechanisms generating them. Just as a di erential equation model of a system can lead to greater understanding, so too can numerical, nonlinear models. The detection of this respiratory uctuation is described in chapter 9. Chapter 7, 8 and 10 describe applications of the modelling algorithm presented in this chapter. Initially we used a radial basis modelling algorithm described by Judd and Mees [62] to model recordings of the abdominal movements of sleeping infants. Although these radial basis models give accurate short term predictions, they were not entirely satisfactory in the sense that simulations of the models failed to exhibit some characteristics of the original signals. After some alteration of the model building algorithm, much better results were obtained; simulations of the models exhibit signals that are nearly indistinguishable from the original signals. In this chapter we rst describe the time series we will model, a review of the nonlinear modelling methods of Judd and Mees [62] may be found in section 2.3. We identify some failings of simulations of models produced by this algorithm; suggest new modi cations that may overcome these problems; and nally demonstrate the improved results we have obtained. We have used data collected from sleeping infants to estimate the correlation dimension of the respiratory patterns [136, 140], and to identify cyclic amplitude modulation (CAM) in respiration during quiet sleep [133]. This work will be discussed in chapters 8 and 9. These studies concluded that linear modelling techniques were unable to model the dynamics of human respiration2 . Furthermore, by comparing the correlation dimen1 This work is presented in chapter 8. 2 By calculating correlation dimension

for data embedded in R3 , R4 and R5 as a test statistic surrogate analysis of 27 recordings of infant respiration from 10 infants concluded that the data were dc ("0 )

75

76

Chapter 6. Nonlinear modelling

Abd. Area

10 5 0 −5

160

180

200

220

240 260 time(seconds)

280

300

320

Figure 6.1: Data: The data we use in our calculations. The solid line represents the data set from which we build our radial basis models. The horizontal axis is time elapsed from the start of data collection and the vertical axis is the output from the analogue to digital convertor (proportional to cross-sectional area measured by inductance plethysmography). Note the sigh (at about 300 seconds) and the onset of periodic breathing following this. The data represented as a solid line is also shown in gure 4.5 and is from group A (section 1.2.2). sion estimates for the data and surrogates we were able to demonstrate that simulations from radial basis models produced dimension estimates that closely resembled that of the data (chapter 8). This implies that nonlinear models are more accurately modelling the data than are linear models. However, these nonlinear models appeared to have diculty with some data sets, most notably those with substantial noise contamination and data exhibiting non-stationarity. In this section we attempt to improve the modelling techniques.

6.1 Modelling respiration In this section we introduce the data set that we will attempt to model. In chapter 2.1 we described the use of correlation dimension estimation and false nearest neighbour techniques to determine a suitable embedding dimension and examined three alternative criteria for embedding lag to deduce an appropriate value. Sections 5.2 and 5.3 demonstrated the calculation of typical values of de and  for reconstruction via time delay embedding. In the following section we brie y describe the data we will examine in this chapter. In section 6.1.2 we use these embedding techniques to reconstruct the dynamical system from these data and apply the nonlinear modelling technique described in section 2.3 and examine the weaknesses of the result.

6.1.1 Data For much of the following sections we illustrate the calculation and

comparison using just one recording, selected because it is a \typical" representation of a range of important dynamical features. The data set we use (see gure 6.1) is from a inconsistent with each of the linear hypotheses addressed by Theiler and colleagues [152].

77

Abd. Area

6.1. Modelling respiration

5 0

Abd. Area

−5 100

150

200

250

550

600

650

300

350

400

450

500

700 750 time(seconds)

800

850

900

5 0 −5 500

Figure 6.2: Periodic breathing: An example of a short episode of periodic breathing after a sigh (at 580 seconds on the second panel). Smaller sighs are also present at about 275 seconds and 470 seconds on the rst panel. The horizontal axis is time elapsed from the start of data collection and the vertical axis is the output from the analogue to digital convertor (proportional to cross-sectional area measured by inductance plethysmography). These data are from group A (section 1.2.2).

78

Chapter 6. Nonlinear modelling

section of approximately 10 minutes of respiration of a two month old female in quiet (stage 3{4) sleep. These data exhibits a physiological phenomenon of great interest to respiratory specialists known as periodic breathing [66, 85]. Periodic breathing is simply extreme CAM | the minimum amplitude decreases to zero. Figure 6.2 shows an example of periodic breathing. In all other respects these data are typical of many of our recordings. The section which we examine rst is from a period of quiet sleep preceding the onset of periodic breathing (see gure 6.1). All data used in this chapter is from group A (section 1.2.2).

6.1.2 Modelling We attempt to build the best model of the form yt+1 = f (zt) + "t where "t is the model prediction error and f : Rd 7! R is of the form

f (zt) = 0 +

n X i=1

iyt;`i +

 cj k ; j+n+1  kzt ; rj j =1

m X

(6.1)

where rj and j are scalar constants, 1  `i < `i+1  d are integers and cj are arbitrary points in Rd . The integer parameters n and m are selected to minimise the description length [110] as described in [62]. Here () represents the class of radial basis function from which the model will be built. We choose to use Gaussian basis functions because they appear to be capable of modelling a wide variety of phenomena. This model, and an algorithm to t it to data, have been described in section 2.3. The data set consists of 20000 points sampled at 50Hz. This is oversampled for our purposes and we thin the data set to one in four points and truncate it to a length of 1600 (see gure 6.1). Using the techniques of section 2.1 and the results of sections 5.2 and 5.3, we set d = 4 and choose  = 5. Trials with the modelling algorithm as described in [62] produced some problems with the model simulations (see gure 6.3). None of the simulations look like the data. When periodic orbits are evident they are still unlike the data; the waveform is symmetric, whereas the data have a de nite asymmetry. Moreover the free run predictions from these models often exhibit stable xed points. This is extremely undesirable as it is evidently not an accurate representation of the dynamics of respiration | breathing does not tend to a xed point, usually. The remainder of this chapter shall be concerned with addressing these problems. These problems are the result of three main de ciencies in the initial modelling algorithm: (i) it over ts the data; (ii) it does not produce appropriate simulations; and (iii) models are not consistent or reproducible. We will attempt to improve upon these problems whilst considering the many competing criteria for a good model.

79

6.2. Improvements Simulation

Free run prediction 2 Abd. Area

Abd. Area

2 0

−2 0

100

200

t

300

400

0 −2 0

100

200

t

300

400

Figure 6.3: Initial modelling results: Free run prediction and noise driven simulation of a radial basis model. The plot on the left is a free run prediction with no noise, on the right isqa simulation p driven by Gaussian noise at 10% of the root-mean-square prediction P t 2 error ( i=1 "i = N ). The horizontal axis is yt for t = 1; : : : ; 500, the vertical axis is the output from the analogue to digital convertor (proportional to cross-sectional area measured by inductance plethysmography). From 30 trials 27 of them exhibited xed points.

6.2 Improvements Before we can attempt to improve our modelling procedure we must be clear on what we mean by improvement. There are several criteria that might be imposed to achieve a \good" model. Modelling criteria measure quantities such as the number of parameters in the model, its prediction error and description length. It is desirable to have a model with few parameters, a small description length and a small root mean square prediction error. Algorithmic criteria are concerned with optimising the modelling algorithm, to ensure that it searches the broadest possible range of basis functions as eciently as possible. Unfortunately a larger search space comes at the expense of more computation. Qualitative criteria consider properties of the dynamics of models; for example, the behaviour observed in the simulations of the model. In modelling breathing, for example, we expect something like stable periodic (or quasi-periodic) solutions; divergence or stable xed points seem unlikely. Furthermore, we expect the shape of the periodic solution to closely match the shape of the data and to occupy the same region of phase space. Modelling results should also be reproducible and representative. It does not seem unreasonable to expect consistent, repeatable results from a modelling algorithm, both qualitatively and quantitatively. Reproducibility can be examined by repeatedly modelling a single data set. Furthermore, the model should be representative in that when making many simulations of the model, we ought to obtain time series of which the original data are representative. Representativity can be measured with the assistance

80

Chapter 6. Nonlinear modelling

of surrogate tests using a statistic such as the correlation dimension estimates or cyclic amplitude modulation. In the following subsections we consider new improvements of the basic modelling procedure by: (i) broadening the class of basis functions; (ii) using a more targeted selection algorithm; (iii) making more accurate estimates of description length; (iv) local optimisation of nonlinear parameters; (v) using reduced linear modelling to determine embedding strategies; and (vi) simplifying the embedding strategies using a form of sensitivity analysis.

6.2.1 Basis functions In this section we introduce a broader class of basis func-

tions. This will produce an algorithm that is capable of modelling a wider range of phenomena. First we expand the embedding strategy so that instead of radial (\spherical") basis functions we introduce \cylindrical" basis functions. Detailed arguments about the advantages of these basis functions are described elsewhere [64]. Generalise the functional form (6.1) to

f (zt ) = 0 +

n X i=1

i yt;`i +

m X j =1

  j +n+1  kPj (ztr ; cj )k ; j

(6.2)

where `i , rj , j , cj , n, m are as described previously and Pj : Rd 7! Rdj (dj < d) are projections onto arbitrary subsets of coordinate axes. The functions Pj can be thought of as a local embedding strategy. Each basis function has a di erent projection Pj and so each kPj (zt ; cj )k is dependent on a di erent set of coordinate axes. These projections Pj are the essential feature of this model that generates the variable embedding which we tentatively de ned in section 5.1. We actually generalise the choice of embedding strategy further by selecting the best lags from the set f0; 1; 2; : : : ; (d ; 1) g, not only subsets of f0; ; 2; : : : ; (d ; 1) g. It seems that by allowing the selection of di erent embedding strategies in di erent parts of phase space the model gives better free run behaviour. This indicates that, naturally enough, the optimal embedding strategy is not uniform over phase space. Selecting from this larger set of embedding lags is equivalent to embedding with a time lag of 1 in Rd . However the modelling algorithm rarely selects more than a d dimensional local embedding. Therefore, these improved results are not contrary to our previous estimates of optimal embedding dimension. They do allow for an embedding in more than 2dc + 1 dimensions (satisfying Taken's sucient condition) if necessary. As noted earlier the choice of embedding lag is largely arbitrary. Furthermore, to increase the curvature of the basis functions we replace the choice of

 ;x2 

(x) = exp 2

81

6.2. Improvements

by



%

~(x; %) = exp (1 ; %) x%

R 1 ~(x; %)dx = where 1 < % < R is the curvature3 and 1;% % is a correction factor so that p12 ;1 1. Hence, maintaining consistent notation ~(x; %) = 

s

!

2(1 ; %) x %2 ; %

and the basis functions become functions of the form

 where

s

%j

2(1 ; %j ) kPj (zt ; cj )k 2

%j

!

rj

(x) = exp ;2x : 2

Broadening the class of basis functions has increased the complexity of the search algorithm. Hopefully it will also have broadened the search space suciently to encompass functions which can more accurately model the data. To overcome this increased search space we consider a more ecient search algorithm.

6.2.2 Directed basis selection The method of Judd and Mees [62] involves randomly generating a large set of basis functions f( kz;r c k )gj = fj gj and evaluating them at each point of the embedded time series z to give the matrix V = [1j2 j   jM ]. j

j

Following an iterative scheme they repeatedly select columns from this matrix (and the corresponding candidate basis function) to add to the optimal model. This is the model selection algorithm described in section 2.3.3. Instead, we select a new set of candidate basis functions fj gj (and a new matrix V ) at each expansion of the optimal model. We then identify the column k of V that best ts the residuals (orthogonal to the previously selected basis functions) and select the corresponding basis function k . All the other candidate basis functions fj gj=1;:::;M ;j6=k are ignored and forgotten at the next iteration. Because a new set of basis functions are selected at each expansion, all the candidate basis functions are much more appropriately placed4 . We have the following algorithm. Algorithm 6.1: Revised model selection algorithm. 1. Normalise the columns of V to have unit length. 3 To

prevent large values of the second derivative of f it is necessary to provide an upper bound

R

on %. 4 Basis functions are selected according to either a uniform distribution or the probability distribution induced by the magnitude of the modelling prediction error.

82

Chapter 6. Nonlinear modelling

2. Let S0 = ( N2 ; 1) ln(y T y=N ) + 12 + ln . Let eB = y and VB = ;. 3. Let  = V T eB and j be the index of the component of  with maximum absolute value. Let VB0 = VB [ fVj g. 4. Generate a new matrix V containing a new set of candidate basis functions fVi gmi=1. Normalise V . 5. Calculate B 0 so that y ; VB B 0 is minimised. Let 0 = V T eB 0 . Let o be the index in B 0 corresponding to the component of 0 with smallest absolute value. 6. If o 6= jVB j, then put VB = VB0 n fVog, calculate B so that y ; VB B is minimised, let eB = y ; VB B , and go to step 3. 7. De ne Bk = VB , where k = jVB j. Find  such that (VBT VB  )j = 1=j T for each j = f1; : : :; kg and calculate Sk = ( N2 ; 1) ln eBNeB +(k +1)( 12 + P ln ) ; kj=1 ln ^j . 8. If some stopping condition has not been meet, then go to step 3. 9. Take the basis Bk such that Sk is minimum as the optimal model. Note that the explication of this algorithm contains a slight abuse of notation, VB is both the set of basis functions fVj gkj=1 and the matrix [V1jV2j   jVk ]. Note that, the essential di erence between this and algorithm 2.1 is that step 4 generates a new set of candidate basis functions each time. As a consequence it is necessary to keep track of the basis functions in the model VB 5 , and not just indices B . The improvement in modelling achieved by this will require greater computation time. Furthermore the selection of basis functions that more closely t the data may, possibly, increase the number of basis functions allowed by the description length criterion. To alleviate this problem we introduce a harsher more precise version of description length.

6.2.3 Description length The minimum description length criterion, suggested

by Rissanen [110], is used by Judd and Mees [62] to prevent over tting. This is the description length criterion described in section 2.3.2. However, the original implementation of minimum description length used by Judd and Mees only provides a description length penalty for the coecient j of each of the radial basis functions (and linear terms). Each basis function also has a radius rj and coordinates cj which must also be speci ed to some precision, and hence should also be included in the description length calculation. In [62] j is j truncated to some nite precision j , then the description length is expressed as

L(z; ) = L(z j) + L() 5 In

practice one will need to record the parameters which determine these basis functions.

(6.3)

83

6.2. Improvements

where

L(zj) = ; ln P (z j) is the description length of the model prediction errors (the negative log likelihood of the errors) and

L() 

mX +n+1 j =1

ln 

j

is the description length of the truncated parameters, is an inconsequential constant. We generalise equation (6.3) and include the nite precisions of rj and cj . Let  represent the vector of all the model parameters (j , cj , and rj ) and  the truncation of those parameters to precision . Then

L(z; ) = L(zj) + L() where

L() 

X

(d+2)m+n+1

j =1

(6.4)

ln  : j

Now the problem becomes one of choosing  to minimise (6.4). By assuming that  is not far from the maximum likelihood solution ^ (see section 6.2.4) one can deduce that k X 1 T ^ L(z; )  L(z j) + 2  Q + k ln ; ln j ; (6.5) j =1 where k = ((d + 2)m + n + 1). Minimising (6.5) gives (as in [62]), (Q)j = 1=j where Q = D L(z j) is the second derivative of the negative log likelihood, with respect to all the parameters. Although algebraically complicated, this expression can be solved relatively eciently by numerical methods. However, by assuming that the precision of the radii and the position of the basis function must be approximately the same6, one can circumvent a great deal of the computational diculty, and simply calculate the precision of rj | assuming the same values for the corresponding precisions of the coordinates cj . Much of the computational complexity of calculating description length could be avoided by utilising the Schwarz criterion (2.15). Indeed, from experience it appears that the Schwarz criterion gives comparable size models. However, Schwarz' criterion does not take into account the relative accuracy of di erent basis functions | an important feature of minimum description length. 6 Since

a slight change in radius will a ect the evaluation of a basis function over phase space in the same way as an equal small change in the position of the basis function.

84

Chapter 6. Nonlinear modelling

6.2.4 Maximum likelihood Once the best (according to sensitivity analysis)

basis function has been selected we improve on its placement by attempting to maximise the likelihood T P (zj;  2) = (212)N=2 exp (y ; V 2)(2y ; V ) where y ; V  = " is the model prediction error, and  2 is the variance of the (assumed P to be) Gaussian error. By setting  2 = ti=1 "2i =N and taking logarithms one gets that

 2 N=2 Xt 2 N ln P (z j) = 2 + ln N + ln "i i=1

!N=2

:

(6.6)

To maximise the likelihood we optimise equation (6.6) by di erentiating ln (

Xt i=1

"2i )N=2

with respect to rj , cj , and j . This calculation is algebraically messy, but computationally straightforward provided a good optimisation package is used7 .

6.2.5 Linear modelling selection of embedding strategy Allowing di erent

embedding strategies from such a wide class (due to the expansion of the class of basis functions in section 6.2.1) increases the computational complexity of the modelling process. However, to circumvent this we note that for Gaussian basis functions the rst order Taylor Series expansion gives 0 qPd 1  kPj (zt ; cj )k  2 p ( z ; c ) i t j i =1 A = @  r r j

j

 d  X j p ( z ; c ) j i t j   rj i=1

Rd

(6.7)

where pi : 7! R is the coordinate projection onto the i-th coordinate. We then build a minimum descriptionh length of the residual of the form (6.7). That i  jpi(zt;model d c ) j j which yield the model with minimum is, we select the columns of  rj i=1 description length. From this we deduce that the basis functions selected are a good indication of an appropriate embedding strategy. Hence, if the minimum description length model consists of the basis functions   jp`(zt ; cj )j  

rj

`2f`1 ;`2 ;:::;`dj g

then we use the embedding strategy f`1; `2; : : : ; `dj g. Although this method is approximate it is hoped that this will provide useful and ecient innovation within the modelling algorithm. 7 Many

potentially useful optimisation packages are available via the internet. At the time of writing this thesis, a list of public domain and commercial optimisation routines was available from the URL http://www.isa.utl.pt/matemati/mestrado/io/nlp.html, and from the newsgroup sci.op-research. In this thesis the author uses an algorithm by Powell [97, 99].

85

6.3. Results Simulation

Free run prediction 2 Abd. Area

Abd. Area

2 0

−2 0

100

200

t

300

400

0 −2 0

100

200

t

300

400

Figure 6.4: Improved modelling results: Free run prediction and noise driven simulation of a radial basis model. The plot on the left is a free run prediction with no noise, on the right is a simulation qPt 2 driven p by Gaussian noise at 10% of the root-meansquare prediction error ( i=1 "i = N ). The horizontal axis is yt for t = 0; : : : ; 500, the vertical axis is the output from the analogue to digital convertor (proportional to cross-sectional area measured by inductance plethysmography).

6.2.6 Simplifying embedding strategies Our nal, very rudimentary alter-

ation is designed to account for some of the approximation required in the reduced linear modelling of the embedding strategies. Given an embedding strategy suggested by the method of section 6.2.5 we generate additional candidate basis functions by using embedding strategies whose coordinates are subsets of the coordinates of the embedding strategy suggested by the linear modelling methods. That is, if section 6.2.5 suggestsan embedding candidate basis func strategy f`1; `2; : : : ; `dj g then we generate j P i (zt ;cj )j tions  using all embedding strategies Pi : Rd 7;! Rdi where Pi projects rj onto the coordinates Xi  f`1; `2; : : : ; `dj g.

6.3 Results After implementing the alterations described in the preceding section, we again apply our methods to the same data set. This section describes the results of these calculations and examines some of the improvements in the nal model. We also examine the individual e ect of each modi cation. and the e ectiveness of this modelling procedure in seven di erent data sets (from six infants). Because of its physiological signi cance, all the data sets selected for this analysis exhibit CAM suggestive of periodic breathing. We compare dimension estimates for the original data sets and simulations from the models. Finally, we apply a linear modelling technique discussed elsewhere [133] to detect CAM within the respiratory traces of sleeping human infants, and present some results. That is, we compare the CAM present in the data following a sigh to that present in the models built from the data preceding the sigh.

6.3.1 Improved modelling Figure 6.4 shows a section of free run prediction,

and noisy simulation for a \representative" model. Using an interactive three dimen-

86

Chapter 6. Nonlinear modelling

Figure 6.5: Cylindrical basis model: A pictorial representation of the interactive 3 dimensional viewer we used. The axes range from ;1:715415 to 3:079051, the same range of values as the data. The point (;1:7; ;1:7; ;1:7) is in the front centre, foreground. The cylinders, prisms and sphere represent the placement (cj ) and size (rj ) of di erent basis functions with di erent embedding strategies: the X , Y , and Z coordinates shown correspond to yt , yt;5 , and yt;15 respectively. The colouring of the basis functions represents the value of the coecients (j ). This representation will be discussed in more detail in section 7.1. The corresponding URL is http://maths.uwa.edu.au/watchman/thesis/vrml/3Dmodel.vrml.

87

6.3. Results 1.5

1

Abd. Area

0.5

0

−0.5

−1

−1.5 0

20

40

60

80 100 120 time (seconds)

140

160

180

200

Figure 6.6: Short term behaviour: Comparison of simulation and data. The solid line for the data, the dot-dashed qPt 2is pa free run prediction, the dashed is a simulation driven by noise (20% of i=1 "i = N ). The initial conditions for the arti cial simulations are identical and are taken from the data. The vertical axis is the output from the analogue to digital convertor (proportional to cross-sectional area measured by inductance plethysmography). sional viewer (see gure 6.58) it is possible to determine that these models also have many more common structural characteristics than those created in section 6.1.2. The size, placement, shape and local embedding dimensions of the basis functions of the models have many similarities. Some observations regarding the physical characteristics of these models is presented in section 7.1 Importantly, all of these models have similar free run behaviour. The free run predictions are as large (in amplitude) as the data; this was a substantial problem with the original modelling procedure. Moreover, the free run behaviour with noise appears more \realistic" and the shape of the simulations mimic very closely that of the data. Figure 6.6 shows a short segment of a simulation, along with the data. Note the similarities in the shape of the prediction and the data. Finally, the simulations exhibit a measurable cyclic amplitude modulation which we use in section 6.3.3 to infer the presence of cyclic amplitude modulation in the original time series. 8 All

the three dimensional gures represented in this thesis are also available on the internet as three dimensional object les. An index of all these gures is currently accessible at http://maths.uwa.edu.au/watchman/thesis/vrml/vrmls.html.

Chapter 6. Nonlinear modelling

88

Modelling nonlinear method parameters A 12.52.4 A+B 12.52.4 A+B+C 24.54.3 A+B+D 10.72.3 A+B+C+D 14.53.5 A+B+C+D+E 9.52.9 A+B+C+D+F 13.73.6 A+B+C+D+E+F 11.03.1 A+B+C+D+E+F+G 11.43.2

 RMS error  q P t "2 =pN

-1086157 -1090155 -1123198 -975191 -909210 -735131 -87081 -990119 -980110

MDL

i=1 i

0.1350.016 0.1130.011 0.1040.015 0.1220.016 0.1230.018 0.1410.012 0.1260.009 0.1170.013 0.1170.011

Free run amplitude 0.000.91 1.2231.90 1.581.04 0.3424.91 1.501.09 1.591.31 1.3117.48 1.1717.94 1.871.00

CPU time (seconds) 155.761.88 152.757.08 308.494.74 391.2295.2 781540.8 1152851.9 27731100 29451294 2663944.9

Table 6.1: Algorithmic performance: Comparison of the modelling algorithm with various \improvements". The seven di erent modelling procedures are the initial routine described by Judd and Mees, and six alterations described in section 6.2. Modelling methods are: (A) the initial method; (B) extended basis functions and embedding strategies; (C) directed basis selection; (D) exact description length; (E) local optimisation of nonlinear model parameters; (F) reduced linear modelling to select embedding strategies; and (G) simplifying embedding strategies. Results are from 30 attempts at modelling data described in section 6.1.1 and gure 6.1. The numbers quoted are (mean value)(standard deviation). Calculations were performed on a Silicon Graphics Indy running at 133MHz with 16Mbytes of RAM. These calculations are identical to those of [135], except that the CPU time has been recalculated on a Silicon Graphics 02 (180MHz clock speed with 64Mbytes of RAM) for direct comparison to the results of table 6.3. CPU time is measure in seconds using MATLAB's cputime command.

6.3. Results

89

6.3.2 E ect of individual alterations Table 6.1 lists some characteristics of

models built from the data in gure 6.1 using various methods. The di erent modelling strategies are: (A) the initial method (described in section 6.1.2); (B) extended basis functions and embedding strategies (section 6.2.1); (C) directed basis selection (6.2.2); (D) more accurate approximation to description length (6.2.3); (E) local optimisation of nonlinear model parameters (6.2.4); (F) reduced linear modelling to select embedding strategies (6.2.5); and, (G) simplifying embedding strategies (6.2.6). These alterations to the algorithm were progressively added in various combinations and characteristics of the observed models measured. The initial procedure (A) produced very bad free run predictions; 27 out of 30 trials produced simulations with xed points. Extending the class of basis functions and adding cylindrical basis functions (B) vastly improved this (only 8 out of 30 simulations did not have periodic (or quasi-periodic) orbits). Most of the periodic orbits in these simulations were smaller than the data (did not occupy the same part of phase space) and one divergent simulation was observed (hence the large standard deviation in table 6.1). This approach decreased the prediction error without a ecting either the model size or description length (clearly, the required precision of the parameters was greater). Directed basis selection (C) greatly increased the size of the model and decreased error whilst improving free run behaviour | not only in amplitude but also shape. The increase in computational time could almost entirely be due to the greater model size. Improving the description length calculation (D) decreased the model size whilst, predictably increasing prediction error. This also caused a surprising increase in calculation time | an indication of the computational diculty solving (Q)j = 1=j when Q is the second derivative with respect to all the model parameters (or at least  and r). Because there is a harsh penalty these models are far less likely to be over tting the data. Combining the improved description length calculation and directed basis selection produced models comparable in both size and tting error to before either alteration was implemented (A+B). However, free run behaviour had an amplitude closer to the mean amplitude of the data and exhibited an asymmetric waveform similar to the data. Addition of the nonlinear optimisation (E) and local linear modelling (F) routines caused the greatest increase to computational time. Individually these methods did not o er any considerable improvement to the other model characteristics. However many of the statistics indicate a decrease in the variation between trials. Combined, these modi cations gave a slight improvement in prediction error and description length whilst making the model smaller. They produced more realistic simulations although the amplitude was smaller than that of the data. Finally, the simple procedure of checking that simpler embedding strategies would not produce better (or equally good) results (G) caused a substantial improvement. This is perhaps due in part to the previous optimisation and local linear methods, par-

90

Chapter 6. Nonlinear modelling subjectM

Abd. Area

10 5 0

−5 −10 450

500

550

600

650

700

time (sec)

Figure 6.7: Periodic breathing: An example of periodic behaviour in one of our data sets. The solid region was used to build a nonlinear radial basis model. Note that periodic breathing begins immediately after the sigh. The vertical axis is the output from the analogue to digital convertor (proportional to cross-sectional area measured by inductance plethysmography). These data are also illustrated as part of a longer recording in gure 6.2. ticularly the approximate nature of the local linear modelling. Removing coordinates helped produce some appreciable improvement in suitability of the embedding strategies suggested by the approximate local linear methods. The local linear methods often produce a high dimensional local embedding (many signi cant coordinates); eliminating some of these will usually only slightly increase the prediction error. This simple addition increases the amplitude to a realistic level (approximately 1:9 whilst the mean breath size for the data is about 2:3 9 ) whilst decreasing the proportion of xed point and divergent trajectories to the lowest level (8 and 0 of the 30 models, respectively) without appreciably changing the description length, prediction error, or model size whilst decreasing slightly the calculation time (and variance in calculation time). Furthermore, these models have far more structural similarities (in the size and placement of basis functions) than the previous models have, indicating that these model are far more consistent. The remainder of this section is devoted to some applications of these modelling methods and tests of their representability.

6.3.3 Modelling results From over 200 recordings of 19 infants, we identi ed

seven data sets from six infants for more careful analysis. All seven of these data sets include a sigh followed by a period of breathing exhibiting cyclic amplitude modulation (CAM). Our present discussion examines the analysis of these data sets. In this section we examine the free run behaviour of data sets created from seven models of seven data sets from six sleeping infants. We compare the correlation dimen9 Note,

however that the data are slightly non-stationary whilst the model is not. Non-stationary models of this data are described in section 7.4.

6.3. Results

91

sion of the data and simulations from models. Following this we compare the period of CAM detected in the free run predictions from the models to that visually evident after a sigh. Figure 6.7 illustrates one of the data sets used in our analysis. This is the only set of data to exhibit periodic breathing, the others merely exhibited strong amplitude modulation after the sigh for 25{60 seconds ( 15{30 breaths). Nevertheless the change that the respiratory system undergoes after a large sigh is of great interest to respiratory physiologists. We examine the system before and after a sigh to determine evident physiological similarities in the mechanics of breathing. For each of our seven data sets, we identify the location of the sigh, and extract data sets of 1501 points spanning 120 seconds preceding the sigh. From these data sets the respiratory rate of each recording was established and the period of respiration deduced. Each data set was embedded in R4 with a lag equivalent to the integer closest to one quarter of the approximate period. We then applied our modelling algorithm. Surrogate analysis To determine exactly how similar data and model simulations are we employ an obvious generalisation of the surrogate data analysis used by Theiler [152]. The principle of surrogate data is discussed in chapter 3 and 4. In the present context, we are not interested in determining what type of system generated the data | at least not at present. A simpler null hypothesis (for example [151, 154]) consistent with the data does not concern us here. What is of greater interest to us is determining if the models really do behave like the data. By calculating models and generating free-run predictions from those models, we are in fact generating surrogate data. The similarity of the value of various statistics applied to data and surrogate can be used to gauge the accuracy of the model. Figure 6.8 shows calculations of correlation dimension estimates (following the methods of Judd [60, 61]) for data and surrogate. Our calculations indicate a very close agreement between the correlation dimension of the data and that of the simulations. In 6 of the 7 data sets the correlation dimension estimate dc ("0) for the data is within two standard deviations of the mean value of dc ("0) estimated from the ensemble of surrogates for all values of "0 for which both converged. In the remaining data set the value of correlation dimension di ered by more than 2 standard deviations only at the smallest values of "0 (the nest detail in the data). In all calculations dc ("0 ) for the data is within three standard deviations of the mean value of dc ("0) estimated from the ensemble of surrogates. With respect to correlation dimension our models are producing results virtually indistinguishable from the data. Detection of CAM Previously [133] we have used a form of reduced autoregressive modelling (RARM) to detect CAM in the regular breathing of infants during quiet sleep (this will be discussed in chapter 9). We apply nonlinear modelling methods here with two aims in mind: to demonstrate the accuracy of our modelling methods; and to further demonstrate that CAM evident during periodic breathing and in response to apnea or sigh is also present during quiet, regular breathing.

92

Chapter 6. Nonlinear modelling

de=3; lag=7.

de=3; lag=10. 3 (normalised) dc

(normalised) dc

4

3

2 −2.5

−2

−1.5 −1 de=4; lag=7.

1 −3

−0.5

4 3

−2 −1 de=5; lag=7.

1

2

−1 0 de=5; lag=10.

1

−1

1

4 (normalised) dc

(normalised) dc

−1 0 de=4; lag=10.

3

1 −2

0

8 6 4 2 −2

−2

4 (normalised) dc

(normalised) dc

5

2 −3

2

−1.5

−1 Bs2t8

−0.5

0

3 2 1 −2

0 Ms1t6

Figure 6.8: Surrogate calculations: Comparison of dimension estimates for data and surrogates. The three gures on the left are dimension estimates (for embedding dimension from 3 to 5, shown from top to bottom) for a model of Bs2t8. The right three plots are similar results for a model of Ms1t6. All surrogates are simulation driven by Gaussian noise with a standard deviation of half the root mean square one step prediction error. Each picture contains one dimension estimate for the data (solid line), and thirty surrogates (dotted). The two data sets used in these calculations are shown in gures 6.1 and 6.7, respectively.

93

6.4. Problematic data

subject

sex

age (months)

A(As4t2) male Bb(Bs2t8) female Bb(Bs3t1) G(Gs2t4) female H(Hs1t2) male M(Ms1t6) female R(Rs2t4) male

6 2 2 1 1 2

model CAM in free run CAM after sigh size (breaths) (seconds) (breaths) (seconds) 8(7) 5{6y 14y 5 25 7(6) 6 9 6 9 6(5) 5 10 5 10 4(3) 5 11 5 9 y y 5(3) 8{9 11 9 13 6(4) none none 5 14.5 8(6) 9 18 8 16

Table 6.2: Periodic behaviour: Comparison of CAM after apnea (apparent to visual inspection), the second set of results, and CAM detected in the models limit cycle, the rst set of results. Data sets Ms1t6 and Bs2t8 exhibited periodic breathing. For each data set marked cyclic amplitude modulation (CAM) occurred after a sigh and was measured by inspection. Radial basis models were built on a section of quiet sleep preceding the sigh, noise free limit cycles exhibited periodicities that were measured in both time and breaths from the simulation. Limit cycles marked with a y were not strictly periodic but rather exhibited a chaotic behaviour. Model size is m + n(m), see equation 6.2. We have built nonlinear models following the methods outlined in this paper of the regular respiration of six sleeping infants immediately preceding seven sighs and the consequential onset of periodic or CAM respiration. For each of these models we produce simulations both driven by Gaussian noise, and without noise. The noiseless simulations approach a stable periodic (or chaotic, quasi-periodic) orbit which may exhibit slight CAM. Table 6.2 summarises the results of these calculations. In all but one data set CAM was present in the free run prediction of the nonlinear model. The absence of CAM in one model may either indicate a lack of measurable CAM in the data or a poor model (these data are illustrated in gure 6.7). All other data sets produced nonlinear models that exhibited CAM, the period of which matched that observed after a sigh during visually apparent CAM.

6.4 Problematic data Even using the new modelling improvements suggested here some data will produce results which are inadequate. Usually the noise driven simulations or the free run predictions will be unsatisfactory. In these situations it is usually a problem with the model being unable to reproduce the form of the noise of the original system. The model assumes i.i.d. Gaussian noise. The noise may be non-Gaussian, or non-identically distributed.

94

Chapter 6. Nonlinear modelling

6.4.1 Non-Gaussian noise Although the modelling algorithm described above

assumes additive noise of the form N (0;  2) an adequate t may be produced for data with non-normal errors. In such a situation it is necessary to then estimate the distribution of prediction errors from the model and use this estimate to generate noise according to the assumed distribution. Having estimated the distribution P (e) = Prob(t < e) (following the methods described by Silverman [127]) one may generate random variates t  P (e) as follows. Ensure that the distribution is bounded t 2 [a; b] and generate (e0 ; p0) 2 [a; b]  [0; 1] uniformly. If p0  P (e0 ) then let  = e0 otherwise, select a new pair (e0; p0) 2 [a; b]  [0; 1].

6.4.2 Non-identically distributed noise If the noise source is not i.i.d. then

the problem is not only to estimate the distribution p(e) but to estimate the ensemble of state space dependent distributions p(e; v ) = Prob(t < ejvt = v ). A substantial simpli cation to this problem is introduced in [140] (see chapter 8) to produce suciently accurate results. One simply assumes t  N (0;  (vt)2 ) and then only needs to estimate (vt).

6.5 Genetic algorithms Genetic algorithms (GA) are a stochastic approach to optimisation of an objective function, without calculating the derivative of that function. They are loosely analogous to the concepts of inheritance, evolution and survival of the ttest. Because these algorithms do not require the evaluation of the derivative of an objective function they may be particularly useful to t a radial basis model to a data set. First we will review the general idea of genetic algorithms and describe the application of this approach to our modelling problem.

6.5.1 Review There are many introductory texts in mathematics and computer

science which cover the theory and application of genetic algorithms (for example [15, 86, 109]). We will brie y review the main ideas in this method. Given the general optimisation problem. max f (x) subject to x 2 X a genetic algorithm will perform a stochastic search of X for an optimum value of f . Let G0  X be an initial population of candidate solutions. From Gk a genetic algorithm will generate a new population Gk+1 according to simple rules analogous to the basic concepts of inheritance, breeding, and mutation. Hence, Gk is called the kth generation. To do this one works not in the space X but in some representation X^ of that space. One requires that there exists a bijective map m : X 7;! X^ such that for all x 2 X the representation m(x) consists of a xed nite number of symbols from a nite alphabet. For example an n place binary representation would consist of a string of n

95

6.5. Genetic algorithms

symbols from the set 0; 1. For X = R this is the obvious representation to choose. A binary representation such as this is the most commonly employed but not necessarily the only representation one may choose. Hence m(x) = a1 a2 a3a4 : : :an where ai 2 A for i = 1; 2; 3; : : : ; n. and A is a nite set of symbols (the alphabet). The n symbols that describe m(x) (and therefore x) are analogous to a gene string in genetics and are called genes. For every organism xj 2 Gk de ne the probability pj = Px2f G(xj )f (x) 10. A mating pool k Mk is generated from Gk by selecting each xj with probability pj . Organisms are then selected from Mk for mating. There are several rule for mating to organisms x; y 2 Gk . Let m(x) = a1 a2 a3 : : :an and m(y ) = b1b2 b3 : : :bn . The simplest approach is to select a random integer l and produce the o spring

a1 a2 a3 : : :al;1 b1 : : :bn and b1b2b3 : : :bl;1 al : : :an of m(x) and m(y ). Alternatively one may cross the representations twice (e ectively repeat the above operation for l1 and l2 , l1 6= l2) or interchange every second symbol. Each mating of two parent organisms will produce two o spring. The method we employ is a generalisation of this scheme we assign a probability pC the crossover rate11 and cross the representations m(x) = a1 a2 a3 : : :an and m(y ) = b1b2b3 : : :bn at the position ` with probability pC for ` = 1; 2; : : : ; n. By mating the organisms in Mk one produces a new pool of organisms Mk . From this pool one mutates every gene of every organism with some (low) probability pM , a mutated gene is replaced with another symbol from the alphabet A. This new set of organisms is the next generation Gk+1 . Hence we have the following algorithm. Algorithm 6.2: Genetic algorithm (GA). 1. Let G0  X be the initial population of organisms. Let k = 0. Let x^ be the ttest individual in G0 . That is, f (^x)  f (x) 8 x 2 G0 . 2. Evaluate f (xj ) for all xj 2 Gk and calculate the pj . If f (x) > f (^x) for any x 2 Gk then replace x^ with x. 3. Select a mating pool Mk according to the probability distribution Prob(xj 2 Mk ) = pj :

10 One

4. Mate pairs of organisms from Mk to produce Mk . 5. For each gene ai of each organisms m(x) = a1 a2 : : :an in Mk , replace the symbol ai with another symbol ai 2 Anai with probability pM .

does not need to employ this particular probability (and often it may be inappropriate to P do so). In general it is only necessary to ensure that pj is such that j pj = 1, pj  0 8 j , and pi > pj , f (xi ) > f (xj ). 11 Typically [86] 0:5  pC  0:8.

96

Chapter 6. Nonlinear modelling

6. Denote the new population as Gk+1 . Increase k by one. 7. If stopping condition has not been met go to step 2. 8. Let x^ be the optimum solution with the value of the objective function given by f (^x). To perform this optimisation it is important to note that there are several parameters involved. The probability pM and the size of the populations Gk and Mk must be speci ed as must the stopping condition and rules for selection for breeding and breeding. Furthermore one must select an appropriate tness function and encoding m of the population. Both of these can have a critical e ect on the performance of the algorithm. Furthermore the general genetic algorithm will allow for a proportion of individual alive at generate k to survive to generate k + 1 (for a discussion of this and other details see [42]).

6.5.2 Model optimisation The rst and most important concern with genetic

algorithms in this context is the following. In general one will wish to optimise over X  Rd. To do this one may bound and partition X (equivalently replace f by f^ such that f^ is constant over small partitions of X ) and only optimise over the discrete and nite set X^. To do this it is natural to assume a binary representation for X with a xed precision. Points on the partition grid may then be represented by xed length binary strings. However, we must concern ourselves with a slightly more complicated search space. We may apply genetic algorithms to either select the best model M of a xed size k or the best model of any size. That is we have one of the following two problems. max eT e subject to M 2 Mk

(6.8)

where e is the prediction error of model M and Mk is the set of all models of size k. Or, max L(z; M ) subject to M 2 M

(6.9)

where L(z; M ) is the description length of the given data set z for the model M and M = S1k=0 Mk . Problem (6.8) is exactly that which we address in section 6.2.4 with a deterministic search algorithm. If one was to instead minimise L(z; M ) subject to M 2 Mk one could tackle a slightly more general problem. However, this modi ed problem and 6.9 are computationally very expensive. Both require the evaluation of the description length (solving (2.12)) at each and every model in the population for each generation. S Furthermore, the search space M of (6.9) must be restricted to Kk=0 Mk (where K  1)

97

6.5. Genetic algorithms

to bound the length of representations of each model. Finally, the calculation and storage of a large number of possible models at each generation could be particularly prohibitive. The implementation we choose is a substantial simpli cation of (6.8), namely max eT e subject to k 2 

(6.10)

Where k is the kth basis function of a model M 2 Mk (the set 1 ; : : :k;1 is xed) and  is the set of all possible basis functions. If one selects Gaussian radial basis functions we may take  = f(cj ; rj ) : cj 2 Rd ; rj 2 R+ g 12 . To generate a bounded nite representation we must replace  by a nite set ~ = fcj ; rj ) : cj 2 B1  B2  : : :Bd ; rj 2 B0 g where Bi is a bounded nite precision (discrete) subset of an interval on the real line (for example the b bit binary representation of an interval). The obvious representation of j 2 ~ is the b(d+1) bit binary string obtained by concatenating the binary representation of cj and rj . For each basis function this will produce a string representing b(d +1) genes. However, with a slight abuse of the genetic algorithm described above we may express j as the d +1 genes f(cj )1; (cj )2; : : : ; (cj )d ; rj g. This substantial decreases the complexity of implementing a code for the bijection m but may also limit the power of the genetic algorithm. However, this representation is somewhat natural as one may suspect that changing a single component of cj or rj would produce sucient innovation to make the search e ective. This is the method we implement.

6.5.3 Results In this section we present some results of the application of the GA

described in section 6.5.2 to the radial basis modelling problem. We present the outcome of this algorithm compared to the original genetic algorithm and some experimental results concerning the e ectiveness of the algorithm to improve the objective function | including the selection of the parameters of the GA. Figure 6.9 shows the results of calculations to determine appropriate parameter values for the genetic algorithm. Table 6.3 reproduces the results of table 6.1 with the addition of a genetic algorithm. In general the GA does not improve the modelling procedure signi cantly. The number of nonlinear parameters is generally lower and the RMS error and MDL are generally larger for models implemented with a genetic algorithm. One exception to this is the models produced with reduced linear modelling to select embedding strategies (F). Models that include reduced linear modelling to select embedding strategy but neither local optimisation (E) or simpli cation of embedding strategies (G) bene t signi cantly from the GA. This indicates that the GA only becomes necessary with the additional complexity of the search space as a result of, the 12 The generalisation

to the form of the basis functions discussed in section 6.2.1 only require additional parameters in this representation. In this case one has  = f(cj ; rj ; %j ; Pj ) : cj 2 Rd ; rj 2 R+ ; %j 2 (1; R); Pj : Rd 7;! Rdj g.

98

Chapter 6. Nonlinear modelling

1.18

improvement

1.16 1.14 1.12 1.1 1.08 1.06 0.1 1

0.01 0.8

0.001 0.6

0.0001 mutation

0.4 0.00001

0.2

crossover

Figure 6.9: E ect of parameter values on the genetic algorithm: Shown is the relative improvement in the tness function for various values of the mutation rate pM and the crossover rate pC . The tness function we used in this trial was the sensitivity of a basis function (x). If e is the model prediction error for the model without the inclusion of the basis function  and (x) is the value that function over the data x, the the sensitivity is given by (x)T e. For each pair of parameter values the GA optimisation was performed 150 times with 50 basis functions in the GA optimisation pool.

nonlinear  RMS error  MDL Free run qPt p 2 parameters amplitude i=1 "i = N 8.867 1.655 0.1352 0.01673 -1091 154.8 0.2272 0.7844 8.867 1.889 0.1135 0.01112 -1084 147 4.212 18.14 20.23 8.299 0.122 0.008937 -875.3 48.38 1.884 0.824 7.633 2.697 0.1231 0.0194 -959.9 221.5 0.813 0.8685 11.3 3.914 0.1321 0.006673 -792.5 34.8 1.952 0.8122 6.633 3.068 0.1441 0.005938 -706.4 31.93 6.836 30.65 14.43 4.248 0.1112 0.008021 -1022 71.99 7.382 32.79 8.6 3.276 0.1181 0.01082 -986.4 108.7 10.17 36.01 10.57 4.569 0.1125 0.0121 -1038 129.2 8.796 25.14

CPU time (seconds) 152.6 49.97 138.3 46.63 952.7 413.3 532.7 464.1 1043 710 1495 991 3519 1333 3690 1611 4786 2946

Table 6.3: GA performance: Comparison of the modelling algorithm with various \improvements". These results all include an additional genetic algorithm to optimise the candidate basis functions. The seven di erent modelling procedures are the initial routine described by Judd and Mees, and six alterations described in section 6.2. Modelling methods are: (A) the initial method; (B) extended basis functions and embedding strategies; (C) directed basis selection; (D) exact description length; (E) local optimisation of nonlinear model parameters; (F) reduced linear modelling to select embedding strategies; and (G) simplifying embedding strategies. Results are from 30 attempts at modelling the data described in section 6.1.1 and gure 6.1. The numbers quoted are (mean value)(standard deviation). Calculations were performed on a Silicon Graphics O2 running at 180MHz with 64Mbytes of RAM. CPU time is measure in seconds using MATLAB's cputime command.

Modelling method A A+B A+B+C A+B+D A+B+C+D A+B+C+D+E A+B+C+D+F A+B+C+D+E+F A+B+C+D+E+F+G

6.5. Genetic algorithms

99

100

Chapter 6. Nonlinear modelling

approximate nature of, the reduced linear modelling techniques to determine embedding strategies. The free run amplitude of models produced with a GA tend to exhibit a greater variation, far more divergent simulations and less realistic periodic orbits. There is a signi cant but irregular increase to computation time due to the implementation of the GA.

6.6 Conclusion We have successfully modi ed and applied pseudo-linear modelling techniques suggested by Judd and Mees [62] to respiratory data from human infants. We found that the initial modelling procedure had some diculties capturing all the anticipated features of respiratory motion (they weren't periodic). Some new alterations to the algorithm proposed by the author and a considerable increase to computational time provided results which display dynamics very similar to those observed during respiration of infants in quiet sleep (not only did the models exhibit a periodic limit cycle, but its shape was very similar to the data). Correlation dimension and the methods of surrogate data demonstrated that the models did indeed produce simulations with qualitative dynamical features indistinguishable from the data. Short term free run predictions appeared to behave similarly to the data. And, most signi cantly, we were able to deduce the presence of CAM in sections of quiet sleep preceding sighs by observing this behaviour in free run predictions of models built from these data. This supports our observations from linear models of tidal volume (see chapter 9) and the observation of a (greater than) two dimensional attractor in reconstructions from data (chapter 8). Based on the results of section 6.3 we are able to deduce that some of the alterations (speci cally extending the class of basis functions, and directed basis selection) improved short term prediction. Other alterations reduced the size of the model (accurate approximation to description length) and improved free run dynamics (extending the class of basis function, local optimisation and linear modelling methods to predict embedding strategies). A combination of these methods is required to produce an accurate model of the dynamics. Section 6.5 described an implementation of a genetic algorithm to further improve the modelling results. This was not successful. The genetic algorithm failed to produce signi cant improvements to the modelling results, except when applied in conjunction with the local linear modelling scheme (F) to determine embedding strategies. This is most probably due to the vast increase in the search space produced by these local linear techniques, and the approximate nature of them. We conclude that the modelling methods presented here and in [62] are capable of accurately modelling breathing dynamics (along with a wide variety of other phenomena, see for example [63]). Furthermore, we have presented some evidence that the CAM

6.6. Conclusion

101

present during periods of periodic breathing (when tonic drive is reduced) is also present, but more dicult to observe, during eupnea (normal respiration).

102

Chapter 6. Nonlinear modelling

CHAPTER 7

103

Visualisation, xed points, and bifurcations In chapter 6 we described a series of original improvements and alterations to an existing modelling algorithm of Judd and Mees [62]. We showed that the methods described in chapter 6 produced satisfactory approximation to the dynamics of the respiratory system measured from the abdominal movements of sleeping infants. Surrogate data techniques have been used to show that simulations from the models and the data have many common characteristics. This will be further expanded upon in chapter 8. Furthermore, we already have evidence that cyclic amplitude modulation (CAM) present after a sigh in many sleeping infants is also present in a model of the data proceeding that sigh (section 6.3.3). Using models generated by the methods described in chapter 6 we now wish to identify other features of interest. In this chapter we examine some physical aspects of the models. We calculate xed points and the associated eigenvalues and eigenvectors. We examine the nonlinear nature of the dynamics of the map and nally we will attempt to t time dependent models to some non-stationary data sets to produce bifurcation diagrams. All the data in this chapter are from group A (section 1.2.2). In this and the next chapter we present application of the modelling algorithm we have described. In chapter 7 we apply these models to characterise some important features of phase space, speci cally: the location of xed points, the eigenvalues and eigenvectors of the xed points, and the general dynamic nature of ow in phase space. We also present a graphical representation of cylindrical basis models, and provide some evidence of period doubling bifurcations in some of these models. Chapter 8 describes the application of these models as a nonlinear surrogate test to determine the general structure of the underlying dynamical system. Using correlation dimension as a test statistic we conclude that our data are dissimilar from a monotonic nonlinear transformation of linearly ltered noise, but is consistent with a two to three dimensional quasi-periodic orbit with additional small scale high dimensional structure. Chapters 9 and 10 concern the application of these models and linear models derived from them to detect CAM.

7.1 Visualisation In this section we discuss some physical characteristics of the models themselves. That is, the values of the various parameters `i , rj , j , cj , n, m in the model described in chapter 6, equation (6.2). To do so we utilise an interactive 3 dimensional viewer and an original representation of cylindrical basis models to examine the data and model. Each basis function has associated with it a position cj , a radius rj and a projection Pj : Rd 7! Rdj . Using these we represent each basis function by a dj -sphere embedded in Rd with centre cj and radius rj , denote this by Sdj (cj ; rj ). The surface of the sphere

104

Chapter 7. Visualisation, xed points, and bifurcations

Figure 7.1: Small basis functions: A three dimensional representation of the basis functions selected to model the data shown in gure 6.1 with the modelling algorithm described by Judd and Mees [62]. The spheres represent the individual basis functions. The embedding used is (yt; yt;5 ; yt;10). Note the small basis function on the left of the picture which would have very localised e ect. The corresponding computer le, created with SceneViewer (VRML) is located at the URL http://maths.uwa.edu.au/watchman/thesis/vrml/small blobs.vrml.

7.1. Visualisation

105

Figure 7.2: Big basis functions: A three dimensional representation of a typical model created by the methods described in chapter 6. This is a model of the same data set as gure 7.1. The embedding strategy used is (yt; yt;1 ; yt;2). Note that there are fewer and larger basis functions (speci cally the cylinder on the right and the large sphere to the left) than in gure 7.1. Furthermore, these basis functions represent a nonuniform embedding. Three cylinders are aligned along the same co-ordinate axis. This represents the same embedding strategy. The corresponding computer le, created with SceneViewer (VRML) is located at the URL http://maths.uwa.edu.au/watchman/thesis/vrml/big blobs.vrml.

106

Chapter 7. Visualisation, xed points, and bifurcations

is given by (

Sdj (cj ; rj ) = x 2 Rd : j (x) = 

s

%j !

2(1 ; %j ) kPj (x ; cj )k 2

%j

rj

)

=1

where j is the j th basis function. We project this surface to a 3 dimensional subspace of Rd and draw Sdj (cj ; rj ) as the corresponding sphere, cylinder or prism. Furthermore, Sdj (cj ; rj ) is coloured according to the value of j . Using this representation one is able to view a projection of the model in Rd into R3 . In chapter 6, gure 6.5 illustrates such a representation for one model of the data illustrated in gure 6.1. Using these techniques we notice several interesting features of these models. Models built using the description length criteria introduced in [62] tend to have a lot of little basis functions covering only a small number of data points (typically 1{3). Often, these basis functions will also exhibit extreme1 values of j . These basis functions therefore may only have a very local e ect and are possibly not important to the dynamics of the original system. They serve only to correct the model at a (very) few embedded points. One could therefore exclude such basis functions from the model and use the model produced only as the sum of the larger basis functions. However, this is exactly equivalent to the harsher description length criterion introduced in section 6.2.3. Figure 7.1 shows an example of a model produced by such methods. Models produced after implementing the improvements discussed in chapter 6 have fewer small basis functions. A more perplexing feature of the models produced after implementing the improvements of chapter 6 is that they are more likely to exhibit particularly large basis functions | having radii several times larger than the data. These functions would certainly be only very slightly nonlinear over the range of the data one is tting and therefore could be used to t very slight nonlinearity in the model. Figure 7.2 shows an example of such a situation. One may also note something that should be apparent by examining the projections Pj . Very often models of a single data set will always exhibit the majority of the basis functions aligned along a speci c set of coordinate axes. There is an obvious preference for some embedding strategies over others. This preference for particular embedding strategies is a comforting and not particularly surprising consequence of the fact that some of the embedding coordinates have a stronger e ect on the future evolution than others [64]. Furthermore, the range of di erent positions and nature of basis functions is far less in the models produced by the methods of chapter 6 than those suggested by [64]. This gives additional evidence that the methods discussed in chapter 6 are more repeatable than the original algorithm. 1 Typically

the value of j for a small basis function over a single data point will be several orders of magnitude larger than the corresponding coecients of the \larger" basis functions.

107

f(y,y,...,y)−y

7.2. Phase space 0.5

0.5

0.5

0

0

0

−0.5

−0.5

−0.5

−1 −2

0

2 y

−1 −2

0

2

−1 −2

y

0

2 y

Figure 7.3: The function f (y; y; : : : ; y ) for three models of a respiratory data set: This gure shows three plots of f (y; y; : : : ; y) ; y against y for three models of the same data set. These three plots are typical of the range of results for models of this data set and for models of any set of respiratory data. Note that although they exhibit a range of di erent behaviours they all have one xed point in the same general location. The di erent results elsewhere are due to the fact that the line (y; y; : : : ; y ) is generally located far from the data | in most cases the data sets we have recorded do not tend to a xed point.

7.2 Phase space Given a model of the form

zt+1 = F (zt ) , (yt+1; yt; : : : ; yt;(d;2)) = (f (zt); yt; : : : ; yt;(d;2)) for the vector variable zt = (yt; yt;1 ; : : : ; yt;(d;1) ) a fundamental property of the function F and the dynamics it produces is the values of z0 such that z0 = F (z0 ), the xed points of F . By examining the associated values of the eigenvalues and eigenvectors of the linearisation DFz0 at z0 one may determine the local stability of F . For a discussion of this see [47]. The xed points of the map F will be points of the form z0 = (y0 ; y0; y0; : : : ; y0) such that y0 = f (y0 ; y0; : : : ; y0). To nd the xed points of F it is simply a matter of solving a scalar function of a single variable. Figure 7.3 gives examples of typical behaviour of this function for models of infant respiration. For each xed point z0 of F one may

108

Chapter 7. Visualisation, xed points, and bifurcations

linearise about z0 and calculate the eigenvalues and eigenvectors of the derivative of F . 2

Dz F (z)jz=z0 =

6 6 6 6 6 6 6 4 2

=

6 6 6 6 6 6 6 4

df dy1 jz=z0

1 0 .. . 0

df dz jz=z0

Id;1

0 0 .. . 0

df dy2 jz=z0

3

0 1 .. . 0

::: ::: ::: ...

:::

df dyd;1 jz=z0

0 0 .. . 1

df dyd jz=z0

0 0 .. . 0

3 7 7 7 7 7 7 7 5

7 7 7 7 7 7 7 5

where z = (y1 ; y2; : : : ; yd ) and Id;1 denotes the (d ; 1)  (d ; 1) identity matrix. The eigenvalues i can be calculated as the solutions of det(Dz F (z )jz=z0 ; iI ) = 0; i = 1; 2; : : : ; d and the corresponding eigenvectors from

Dz F (z)jz=z0 vi = ivi:

7.2.1 Results Data from 16 healthy infants were recorded during quiet sleep on

four separate occasions at 1, 2, 4 and 6 months of age. These data are from group A (section 1.2.2). For each of 56 data sets of respiratory movement during quiet sleep we built a cylindrical basis model following the methods described in chapter 6. All these models exhibited a periodic or quasi-periodic limit cycle2 , and they all had at least one xed point. Only 10 of the models exhibited more than one xed point. All data sets exhibited a xed point situated approximately in the centre of the (quasi-)periodic orbit. The line f (y; y; : : : ; y ) = y will pass through the periodic orbit. In 52 cases the leading (largest) eigenvalue 1 of that xed point was complex with Re (1) < 13. The remaining 4 models had a largest eigenvalue which was real with j1j  14 . This indicates that in almost all cases these models exhibit a stable focus. The 4 exceptions also exhibited some rotational e ect but not in the direction of the largest eigenvalue. Whilst these results are important it must be noted that the xed point is situated far from the data (see gure 7.4). Hence we should conclude that these models typically have a stable focus situated approximately in the \centre" of the \quasi-periodic orbit" of the data. 2 By quasi-periodic limit cycle we mean

a quasi-periodic orbit asymptotically covering the surface of a solid homeomorphic to a torus. That is, trajectories lie on the surface of a torus like solid and are typically not self intersecting. 3 However j1 j > 1 in 51 cases 4 The values were 1 = ;0:914; 0:859; 1:204; ;1:488.

7.2. Phase space

109

Figure 7.4: A sample model: The data set and the location of the xed point (the small dot in the centre) of a model of that data set. The lines radiating from the xed point represent the direction of (the real component of) the leading eigenvectors together with the relative magnitude of the eigenvalues. A three dimensional computer le representation of this gure is located at the URL http://maths.uwa.edu.au/watchman/thesis/vrml/fixedpts.vrml.

110

Chapter 7. Visualisation, xed points, and bifurcations

7.3 Flow Characterising the behaviour at the xed points of the model F is important, but it is also particularly dicult. The data from which the model is built are situated far from the xed point. The behaviour which is of greater signi cance, and easier to examine5 is that near the data. A noisy periodic or quasi periodic orbit is present in almost every model of every stationary (or \nearly stationary") data set. In this section we present a new qualitative analysis of some features of that behaviour and the asymptotic approach to the limit cycle of these models. The model F is a map (discrete dynamical system). This map has been calculated to approximate the ow of the underlying (undoubtedly) continuous dynamical system of the human respiratory system. We use the map of the model F to approximate this ow. Figure 7.5 shows a typical ow for a model exhibiting a periodic orbit. This is the type of behaviour exhibited by most models of most data sets which exhibit periodic orbits. Models exhibiting quasi-periodic orbits exhibit behaviour more similar to that of gure 7.6. Note that in gure 7.5 the initially small ball of points is squashed to a two dimensional subset of this embedding space and stretched away from the limit cycle. Furthermore, this \stretching" is nonlinear and creates a bend in the \tail" of the set of points. Figure 7.6 shows an example of a more complicated behaviour. One can see that the initial ball of points is attened stretched and bent due to the more rapid movement of the point near the quasi-periodic orbit. The set of points is then folded and eventually squashed down upon itself (at the top right hand corner of the illustration) in a manner analogous to the stretching and folding of the baker's map [25]. The baker's map f : [0; 1]  [0; 1) 7;! [0; 1]  [0; 1) can be de ned by

(

f (x; y ) =

(a1 x; by1 ); y < b1 1 ; y (a2(1 ; x); b2 ); y  b1

where a1 + a2 < 1 and b1 + b2 = 1 6. This phenomenon is also similar to the continuous stretching and folding exhibited by the Rossler system [113, 41]. Figure 7.7 compares the e ects of the maps used in gure 7.5 and gure 7.6.

7.3. Flow

111

Figure 7.5: Periodic model ow: Every second iteration of a small ball of points as it approaches the limit cycle (the solid lines) of a model of the data set of gure 6.1 (the small dots). The embedding used is (yt; yt;5 ; yt;10). This plot shows every second iteration of a small ball of points from the initial state to the 24th iteration. Note that as the ball is iterated it is squashed down onto two directions and stretched along the limit cycle. The stretching appears initially to by away from the limit cycle (indicating an unstable, and unobservable limit cycle) however the stretching is actually along a direction which moved toward the limit cycle (see the left hand side of the gure). Furthermore the tail of the \comet like" shape is bent by the slower dynamics away from the limit cycle. The corresponding computer le is located at http://maths.uwa.edu.au/watchman/thesis/vrml/flow1.iv.

112

Chapter 7. Visualisation, xed points, and bifurcations

Figure 7.6: Chaotic model ow: Every second iteration of a small ball of points as it approaches the limit cycle (the solid lines) of a model of the data set of gure 6.1 (the small dots). The embedding used is (yt ; yt;5; yt;10). This plot shows every second iteration of a small ball of points from the initial state to the 24th iteration. Note the stretching and folding behaviour. The initial ball of points is stretched and folded to resemble a boomerang (front, bottom, centre of the gure) the \wings" of which are then folded in on themselves (top, right corner of the limit cycle). The corresponding computer le is located at http://maths.uwa.edu.au/watchman/thesis/vrml/flow2.iv.

113

7.3. Flow

x3

0

−0.2 −0.15

−0.2

−0.25

−0.3

−0.35

−0.4

−0.65

−0.6

x2

−0.55

−0.5

−0.45

−0.4

x1

x3

−0.8

−1

−1.2 −0.9 −1 −1.1 −1.2

−1.1

−1

−1.05

x2

−0.95

−0.9

x1

x3

−0.5

−1

−1.5 −0.6 −0.8

−0.8

−1

−1

−1.2 −1.4 x2

−1.2 x1

Figure 7.7: Model ow: The three plots are (from top to bottom): the initial ball of points used in gure 7.5 and 7.6; the 24th iteration of the ball of points under the map of gure 7.5; and the 24th iteration of the same points under the map of gure 7.6. The embedding used is (yt ; yt;5; yt;10). Note that the map of gure 7.5 simply attens stretches and bends the initial ball, the map of gure 7.6 actually folds these points.

114

Chapter 7. Visualisation, xed points, and bifurcations

6

(a)

4

2

0 0

20

40

60

80

100

120

3

(b)

2

1

0 −1.71541

−0.516798

0.681818

1.88043

3.07905

2

2.125

2.25

2.375

2.5

1 2.25

2.28125

2.3125 bifurcation parameter

2.34375

2.375

2.5

(c)

2

1.5

1

2.5

(d)

2

1.5

Figure 7.8: The bifurcation diagram: Panel (a) shows the tidal volume (the di erence between peak inspiration and expiration) of the 131 breaths that occurred during the data set used to build the model. The data set is the same as that shown in gure 6.1. Each of panel (b), (c), and (d) show the asymptotic values of tidal volume which occurred in free run predictions (no noise) of the model for xed values of the bifurcation parameter  (t). The horizontal axis is  (t). Panels (c) and (d) are enlargements of plots (b) and (c), respectively. The region of the enlargement is shown by the dashed vertical lines. The horizontal axes in (a) is breath number, but this corresponds to the value of  (t) shown in (b).

115

7.4. Bifurcation diagrams

7.4 Bifurcation diagrams Models of the form discussed in chapter 6 are stationary and work under the assumption that the data are stationary. However in many complex systems, including physiological ones, this is not always the case. These models may be generalised so that instead of

zt+1 = F (zt ) = (f (zt); yt; : : : ; yt;(d;2)) as in (7.2) one builds a new model in which time is explicitly a parameter

zt+1 = F (zt;  (t)) = (f (zt;  (t)); yt; : : : ; yt;(d;2)):

(7.1)

The nonlinear modelling algorithm one uses to t F (actually f ) to the data should be able to model the transformation  so that one can build a model zt+1 = F (xt ; t). However, for ease of computation we apply an ane transformation  to t so that  (1) = min (yt) and  (N ) = max (yt ). One may think of  (t) as the bifurcation parameter of the model F and in general choose  to be a nonlinear transformation that represents the changing behaviour of the system. It need not even be monotonic. A similar approach has been applied by Judd and Mees [63] to model the chaotic motion of a string and infer the presence of a Shil'nikov mechanism [41, 124, 125, 126]. This additional parameter has the e ect of adding an extra dimension and stretching out the data in phase space. Hence the original (quasi-)periodic orbit occupied by the data has become a thin helix through phase space and the problems associated with modelling it have also increased. However, in this section we build a model of the form (7.1). The data set we use is the same as in chapter 6. It has been illustrated in gure 6.1. From this data set we build a model with the bifurcation parameter  (t) constrained to be a simple ane transformation of sample time. From this model we xed  (t) and observed the asymptotic behaviour of F (;  (t)). The results of gure 7.8 clearly show that the amplitude of the limit cycle (equivalently, the Poincare section of F (;  (t))) undergoes a period doubling bifurcation and degenerates to chaos precisely before the sigh in this recording and the onset of apnea [65]. Repeated application of this modelling method to the same data set was unable to produce identical results. Similar results were obtained but not with identical features 5 At

least in a qualitative sense. In chapter 10 we discuss a quantitative analysis of this behaviour and the problems inherent in those approaches. Chapter 9 presents a method of linear approximation which has lead to substantial success. 6 The baker's map is a two dimensional, injective variant on the tent map ( 2x; x < 21 f (x) = 2 ; 2x; x  12 However, the baker's map is discontinuous. The phenomenon we observe in gure 7.6 is continuous.

116

Chapter 7. Visualisation, xed points, and bifurcations

and not on every occasion. Hence, although this is an interesting and particularly appealing phenomenon we are tempted to treat it as an artifact of the modelling process, and not representative of the data. These calculations show that such a spectacular bifurcation o ers an acceptable model for respiration prior to the onset of apnea. This model exhibits qualitative and quantitative features of the data, simulations from this model has the same features as the data. Hopf bifurcations have been o ered by other authors [17] as an explanation for phenomena, including periodic breathing, in respiration. Unlike our models, these systems are constructed to share some qualitative features with the data and have (by construction) the necessary bifurcation. The period doubling bifurcation we observe in gure 7.8 is not a consequence of the form of model we choose to examine, it is a property of the t of equation (7.1) to the data. We are not programming these features into the model, we extract them from the data. We believe that the model which produced the bifurcation diagram of gure 7.8 o ers a far superior t to this data. It shares more qualitative similarities with the data the possible arti cial systems. However, it is not the only acceptable explanation | in chapter 6 we showed that models with no explicit time-dependence o ered a satisfactory representation of this data set.

7.5 Conclusion In this chapter we presented a characterisation of several features of the hypothesised generic dynamics of respiration based upon the qualitative and quantitative features of models of respiratory data. We demonstrated a new method by which one can visualise these complex cylindrical basis models, and using this we drew conclusion about the modelling algorithm itself. In particular, we demonstrated that the modelling method described by Judd and Mess [62] often over ts the data. Some basis functions had an e ect on only a very few number of data points | fewer than the number of parameters required to specify those basis functions. We demonstrated that not only did the modelling methods described in chapter 6 avoid this but they were more able to t particularly large basis functions to account for subtly slight nonlinearities evident in the data. In section 7.2 we made some general comments about the nature of the phase space of models of these data. In general these models will exhibit a periodic or quasi periodic orbit and at least on xed point. That xed point (on the line f (y; y; : : : ; y ) = y ) will lie in the \centre" of the periodic orbit and has complex eigenvalues with the magnitude of the real part less than one (in almost all cases this occurs with the largest eigenvalues). Hence the xed point of this system exhibits a stable focus in at least two directions. Using a three dimensional viewer we made a qualitative examination of features of this (quasi-)periodic orbit and showed two typical type of behaviours. One associated with periodic orbits, and one with chaotic quasi-periodic orbits. For models exhibiting periodic orbits we showed the presence of stretching and twisting as points

7.5. Conclusion

117

approach the attracting set. For models which exhibit chaotic quasi-periodic orbits this behaviour is further exaggerated, the stretching and twisting becomes stretching and folding in a manner analogous to the baker's map. The analysis of these features has been mainly qualitative, in chapter 9 and chapter 10 we examine some linear and nonlinear (respectively) quantitative methods of describing features associated with cyclic amplitude modulation (CAM). Finally, we built a new type of cylindrical basis model, extending the methods of chapter 6 and incorporating time as a state variable. Some of these models exhibited complex time dependent behaviour, and in models built on data recorded immediately before a sigh and switching to periodic breathing we demonstrated the presence of a period doubling bifurcation leading to chaos.

118

Chapter 7. Visualisation, xed points, and bifurcations

CHAPTER 8

119

Correlation dimension estimates This chapter describes and summarises a study of infant breathing using data analysis techniques derived from dynamical systems theory. We apply correlation dimension estimation techniques (section 2.2), linear surrogate tests (chapter 3), and nonlinear surrogate tests (chapter 4) using cylindrical basis models (chapter 6) to data of infant respiratory patterns. Such techniques have been useful for examining other complex physiological rhythms such as heart rate, electroencephalogram, parathyroid hormone secretion and optico-kinetic nystagmus and can distinguish variations that are random from those that are deterministic. Section 1.1.3 is a critical discussion of recent applications of these techniques. A similar study with di erent data was reported in [136], in this chapter we describe a generalisation of the study reported in [140]. Some of these methods were presented in a preliminary form in [133]. Most studies of the dynamical behaviour of biological systems have used fractal dimension estimation to try to establish that a system's behaviour is chaotic or to classify distinct types of behaviour by their complexity. Recent studies have suggested that respiration in man is chaotic. If that is the case, then techniques derived from DST should allow the dynamical structure of respiratory behaviour to be better described thus improving our understanding of the control of breathing. However, these earlier studies have important limitations. Most studies have used the Grassberger and Procaccia algorithm [44, 45] for estimating fractal dimension, which is simple and easy to implement. Unfortunately, it is now recognised [60, 107] that this algorithm has some technical problems that can lead to misinterpretations of data (see section 2.2). The most serious problems occur with small data sets or when the system incorporates a substantial noise component. The study reported here employs the estimation algorithm of Judd [60] to determine fractal dimension. This analysis is technically more complex, but is in practice more reliable, more robust under the restrictions of nite data, and less prone to misinterpretation. Estimates of fractal dimension are used in identifying the dynamical system that produced the data we have measured. From dimension estimations we conclude that the dynamics of breathing during quiet sleep are consistent with a large scale, low dimensional system with a substantial small scale, high dimensional component i.e., a periodic orbit with a few (perhaps two or three) degrees of freedom supplemented by smaller more complex uctuations. The nature of the low dimensional system is investigated further by constructing surrogate data, which enabled us to test whether the dynamics were consistent with linearly ltered noise or a nonlinear dynamical system. When testing for nonlinear dynamics one also needs to admit the possibility of some combination of linear and nonlinear, deterministic and stochastic components. Our class of nonlinear dynamical systems must also include linear systems and admit the possibility of a noise component.

120

Chapter 8. Correlation dimension estimates

The nonlinear models we use here to test for nonlinear determinism include such a combination of linear and nonlinear, deterministic and stochastic e ects (chapter 6). Our results show clearly that in almost all cases, the dynamics are best described as a low-dimensional nonlinear dynamical system being driven by a high-dimensional noise source. In all cases where such a model is inconsistent with the data, the measured data have strong indications of non-stationarity, that is, the breathing patterns changed during the recording (for example, a sudden switch to periodic breathing occurred). Following a brief introduction to the new dimension estimation algorithm, we describe the experimental methodology, including a description of our surrogate data generation methods. Finally, we discuss the dimension calculations and the results of the hypothesis testing using the surrogate data sets.

8.1 Methods Using standard non-invasive inductive plethysmography techniques we obtained a measurement proportional to the cross sectional area of the chest or abdomen, which is a gauge of the lung volume (see section 1.2). The present study collected measurements of the cross-sectional area of the abdomen of infants during natural sleep. The study was approved by the Princess Margaret Hospital ethics committee.

8.1.1 Subjects Ten healthy infants were studied at 2 months of age, in the sleep

laboratory at Princess Margaret Hospital.1 Data recorded from these infants constitute group A (section 1.2.2).

8.1.2 Data collection The experimental scheme is described in section 1.2. In

this section we make some relevant observations about the collection of data for this study. The 27 observations used to calculate dimension where selected based on sleep state (quiet, stage 3 ; 4 sleep) and then on the basis of sucient stationarity and a minimum of four minutes in length. From each of these 240 seconds of stationary data (the 240 seconds which had the most stationary moving average) were used to calculate dimension. All 27 observations used to calculate dimension are between 240 and 360 seconds, those used to identify CAM are between 400 and 1400 seconds. In contrast to the study by Pilgram and colleagues [95], that examined breathing in REM sleep, we have studied infants in quiet sleep. From measurements of electroencephalogram, electromyogram and electrooculogram, sleep stage was determined using standard polysomnographic criteria [7]. During quiet sleep breathing often appears relatively regular. The possibly chaotic features of most interest are the small variations 1 The

study reported in [136] employed more data over a wider range of physiological conditions. In that study thirteen healthy infants where studied at 1 month of age, in the sleep laboratory at Princess Margaret Hospital. A further nine infants where studied at 2 months. Eight of the infants where studied at both ages. Data were collected and analysed from infant in all sleep states at 2 di erent ages. In the study described here all calculations are performed on 2 month old infants in quiet sleep (stage 3{4).

121

8.2. Data analysis

from this regular periodic behaviour. Because we wish to observe such ne detail we did not lter signals. The analogue output of the respiratory plethysmograph (operating in its DC mode) has no built in ltering. Filtering methods, such as linear lters and singular-value decomposition methods [95], can remove some features that we wish to observe. Furthermore, ltering (even to avoid aliasing) has been shown in some cases to lead to erroneous identi cation of chaos [84, 92].

8.2 Data analysis In this study we employed three main analysis methods: correlation dimension estimation and surrogate data analysis. This section will provide a description of these methods as they are applied here. The mathematical detail has been described in the preceding chapters. First we discuss correlation dimension estimation and then we will provide an overview of surrogate data techniques.

8.2.1 Dimension estimation For a detailed discussion of generalised fractal

dimension and estimation of correlation dimension dc see section 2.2. The estimation algorithm used for the calculations in this chapter is described in detail by Judd [60, 61], an alternative treatment may be found in (for example) [58]. One important advantage of the new method is that it is possible to calculate error bars for dimension estimates. The con dence intervals on the dimension the algorithm provides are dependent on the length of the time series. For each time series the dimension was calculated for time-delay embedding (see section 2.1) in 2, 3, 4, 5, 7, and 9 dimensions. A far greater range than necessary, but one which encompasses suitable values of embedding dimension suggested by false nearest neighbour methods (section 2.1.1). Hence, for each data set our dimension estimation methods produced a graph with many lines on it. Each line on the graph is the dimension estimate for the same data set with a di erent embedding dimension. These lines are a plot of the change in correlation dimension (vertical axis) with scale (horizontal). Scale is calculated as the logarithm of \viewing scale", so moving to the right on a plot indicates increasing scale. The right hand end of the plots is the estimate of dimension at the largest scale (the most obvious features) whereas the left hand end is the dimension estimate at the smallest scale (the nest details).

8.2.2 Linear surrogates Estimating the dimension of the data set gave valuable

information about the geometric structure of that data, but dimension estimation alone is not enough to give a sure indication of the presence of low dimensional chaos or even nonlinear dynamics. Any experimentally obtained data will include some observational noise and when added to a deterministic linear process, can produce dimension estimates not dissimilar to the results of our calculations.

122

Chapter 8. Correlation dimension estimates

To determine if our results indicate the presence of anything more complicated than a noisy linear system we employed the surrogate data methods described by Theiler [152]. Standard linear surrogate techniques were discussed at some length in chapter 3

8.2.3 Cycle shued surrogates Similarly we generated surrogates according

to Theiler's cycle randomising method [151, 154] (section 3.3) to test for any temporal correlation between cycles. Unlike epileptic electroencephalogram signals (which have regular sharp spikes) many data sets do not have a convenient point at which to break the cycles. It is important to separate the cycles at points which will not introduce non-di erentiability that is not present in the original data. For our data we split the data at maximum and minimum value, as respiratory data have reasonably at peaks and troughs. We also split mid inspiration (inhalation) as the gradient is fairly constant over this part of the respiratory cycle. To split the cycles we rst must decide on an appropriate place to break them. Three obvious candidates are at the peak and trough values (where the data are relatively

at) and mid inspiration (where the gradient is steep and almost constant). Figure 8.1 illustrates these three di erent methods for a relatively regular data set (irregular data results in more non-stationary surrogates).

8.2.4 Nonlinear surrogates For each set of data we have calculated its corre-

lation dimension. Using a slight generalisation of the modelling algorithm described in chapter 6 we constructed a cylindrical basis model of the data. We build a model of the form

yt+1 = f (vt ) + g (vt)t ;

(8.1)

where vt is a d-dimensional embedding the scalar time series yt and t are Gaussian random variates. Observe that by using a time-delay embedding the only new component of vt+1 that the model needs to predict is yt+1 (for these models embedding lag  = 1). Both f and g are distinct functions of the form d X

n X

 j  1 ;  k P ( v ;  ) k j j t j a0 + bi yt;i + j exp  ; j j i=0 j =1 

(8.2)

where a0, bi, j , j and j are scalar constants, j are arbitrary points in Rd and Pj are projections onto arbitrary subsets of coordinate components. Such a model is called a pseudo-linear model with variable embedding and variance correction. For computational simplicity we set j = 2 for all j in the function g . The precise meaning of most of these parameters is not important, the parameters can change greatly without a ecting the actual behaviour of the model. Some models of the form described in chapter 6 left non-identically distributed modelling errors (section 6.4.2). These models implied that the system exhibited state dependent noise. Models of the form 8.1 produced simulations (noise driven free run predictions) suciently similar to the data.

123

8.2. Data analysis

data −2

−2.5 0

500 Shuffled − maximum 1000

1500

500 Shuffled − mean value 1000

1500

500 Shuffled − minimum 1000

1500

500

1500

−2

−2.5 0 −2

−2.5 0 −2

−2.5 0

1000

Figure 8.1: Cycle shued surrogates: Examples of cycle shued surrogates and the data used to generate them. The three surrogates have had the cycles split at the peak, mid inspiration (upwards movement), and at the trough. Note that the data are slightly more stationary than the surrogates. These surrogates are typical of those generated from this data set. In many other data sets however the stationarity was more pronounced in the surrogates whose cycles were split at the troughs. Most data sets exhibited greatest non-stationarity in surrogates generated by splitting at the peaks. The degree of stationarity is re ected in the correlation dimension estimates (see gure 8.7).

124

Chapter 8. Correlation dimension estimates

The embedding parameters utilised in these models are the same as those described in section 2.1. We build cylindrical basis models with a time delay embedding using de = 4 and  = 14 (approximate period)  ( rst zero of autocorrelation) according to the methods described in chapter 2 and 5. These models will typically produce free run predictions (iterated predictions without noise) that exhibit periodic or almost periodic orbits. The addition of dynamic noise will produce simulations (iterated predictions with noise) that exhibit behaviour similar in appearance to the experimental data. Figure 8.6 gives an example of some data generated by the methods we use. From each model we generate surrogates as noise driven simulations of that model. Some theoretical concerns with this type of surrogate generation was discussed in chapter 4. We demonstrated that statistics based on the correlation integral are pivotal (proposition 4.1) provided they can be reliably estimated. In the analysis described here we calculated the correlation dimension curve for each set of surrogate data for each of de = 3; 4; 5. We expect our data to be most consistent with some type of nonlinear dynamical system. Before considering this type of surrogate it is necessary to determine if a simpler description of the data would be sucient. To do this we compared our data to surrogates generated by the traditional (linear) methods (see section 3.2). Many studies in biological sciences have employed these traditional surrogate methods (in particular [3, 100, 118, 156, 168]). These methods determine if experimental data are signi cantly di erent from speci c (broad) categories of linear systems. In addition to these linear surrogate tests, we applied a new more complicated nonlinear surrogate test [137, 134]. This method was used to determine if the data are distinguishable from that generated by a broad class of nonlinear models (see section 4.1.3 and 4.3).

8.3 Results We rst present our results from applying our dimension estimation algorithm. Following this we describe the results of our surrogate data and RARM calculations.

8.3.1 Dimension estimation The results of the calculations of dc("0), as shown

in gure 8.2, can be summarised as follows. All calculations fall into two broad categories. Most of the estimates of dc ("0 ) produced curves that increase, more or less linearly, with decreasing scale log "0 but some showed an initial decrease in dimension before increasing with decreasing scale ( gure 8.2, subjects 1 and 4). For any particular data set it was generally found that the the graph of dc ("0) was shifted to higher dimensions as the embedding dimension was increased, although the shape of the graph varied little with changes in embedding dimension. In nearly all cases the dimension estimates at the largest scale lay between two and three. The more or less linear increase in dimension with decreasing scale "0 , and the shift to higher dimensions as the embedding dimension is increased, are both indications

125

8.3. Results

Subject 2

Subject 3 4

4

4

3.5

3.5 3 2.5

Dimension

5 Dimension

3 2 1

2

0

−2.5 −2 −1.5 −1

−2.5 −2 −1.5 −1 −0.5

Subject 5

Subject 6 4.5

3.5

Dimension

Dimension

Dimension

2

3 2.5

1

2

3 2.5 2

−2.5 −2 −1.5 −1 −0.5

Subject 7

−3

Subject 8

Dimension

3 2 1

−2

−1

Subject 9

4.5

4 Dimension

4 3.5

1.5

0 −2.5 −2 −1.5 −1 −0.5

0

2

−2.5 −2 −1.5 −1 −0.5

4

3

2.5

1.5

Subject 4 4

3

6

4

Dimension

Dimension

Subject 1 4.5

3.5 3 2.5

5 4 3

2 −2

−1.5

−1

−0.5

−2 −1.5 −1 −0.5

2 −4

−3

−2

Dimension

Subject 10

4 3 2

−2.5

−2 −1.5

−1 −0.5

Figure 8.2: Correlation dimension estimates: Correlation dimension estimates for one representative data set from each of the ten subjects. Any data sets that produced dimension estimates dissimilar to those illustrated here are discussed in the text (see section 8.3.1) The plots are of scale (log "0 ) against correlation dimension with con dence intervals shown as dotted lines (often indistinguishable from the estimate). Correlation dimension estimates where produced for embedding dimensions of 2, 3, 4, 5, 7 and 9 for all data sets except subjects 2, 4, and 7. Subjects 4 and 7 failed to produce an estimate for the 9 dimensional embedding. Subject 2 did not produce an estimate when embedded in 3 or 9 dimensions. All other dimension estimates are illustrated; higher embedding dimension produces larger correlation dimension.

126

Chapter 8. Correlation dimension estimates Data Dimension

6

3

4

2.5

2

2

0

1.5

−2 0

−2 50

100 150 time (sec)

−1

0

200

Figure 8.3: Dimension estimate for subject 8: One of the data sets used in our analysis. The periodic breathing caused the dimension estimates (the dimension estimates used embedding dimensions of 2, 3, 4, 5, 7, and 9) at large scale to increase. that the system, or measurements, have a substantial component of small scale high dimensional dynamics, or noise, at small to moderate scales. The increase of dimension with decreasing scale is an obvious e ect of high-dimensional dynamics or noise. The shifting to higher dimensions with increasing embedding dimension occurs because in higher-dimensional embedding the points \move away" from their neighbours and tend to become equidistant from each other, which in e ect ampli es, or propagates, the small scale, high-dimensional properties to large scales. (This e ect is related to the counterintuitive fact that spheres in higher-dimensions have most of their volume close to their surfaces rather than near their centres as is the case in two and three dimensions.) Some of the dimension estimates, particularly in two and three dimensions, produced curves which linearly increased for large length scales, but appeared to level o as length scale decreased. For most of the estimates we have computed this is the case when the data are embedded in two dimensions. Furthermore for these embeddings in two dimensional space the correlation dimension estimate seemed to approach two. This indicates that as we look \closer" at the data (that is, at a smaller length scale), it appears to ll up all of our embedding space. For many of the dimension estimates ( gure 8.2, subjects 7 and 9) the embedding in three dimensions also levelled at values slightly less than three. This behaviour can be attributed to an attractor with correlation dimension of approximately 2:8 to 2:9. However, it is probably more likely that this too is simply due to the data \ lling up" the three dimensional space. This is consistent with the results of our false nearest neighbour calculations which suggested that three or four dimensional space would be required to successfully embed the data. There is one particular estimate which appeared to behave quite di erently to all the others. Some of the curves of the estimates for subject 8 appeared to increase, decrease,

127

8.3. Results Data 4

Dimension 3

2 2 0 1 −2 0

50

100 150 time (sec)

−3

−2

−1

200

Figure 8.4: Dimension estimate for subject 2: One of our data sets along with the dimension estimates (shown are the estimate with an embedding dimension of 2, 3, and 4). Note the large sighs during the recording and the corresponding increase in the dimension estimate at moderate scale. Another data set from the same infant exhibited similar behaviour and produced a similar dimension estimate. and then increase again2 . This could indicate that as we look closer at the structure there is some length scale for which the embedding structure seems to be relatively high in dimension, whilst by looking at an even small length scale the behaviour has signi cantly lower dimension. These observations are supported by what we can observe directly from the data. This time series includes an episode of periodic breathing | increasing the complexity of the large scale behaviour (see gure 8.3). Similarly, some of the data sets for subject 2 include large sighs causing the dimension estimate to increase at large scales (see gure 8.4). Finally, the remainder of the estimates (for example gure 8.2, subjects 1, 2 4, 6, 7, 8 and 10) behaved in yet another manner. These estimates are approximately constant for a small range of large length scales and gradually increased over small length scales. The estimates at large length scales were generally about two to three, indicating that the large scale behaviour is slightly above two dimensional. The increase in dimension estimate for smaller length scales can again be attributed to either noise or high dimensional dynamics. However, the scale of \small scale structure" in the dimension estimates is at a larger scale than the instrumentation noise level. Typically the smallest scale is ln("0 )  ;2:5, a scale of approximately 5% of the attractor (e;3  0:049787  0:05). The digitised signal will typically use at least 10 bits of the AD convertor (2;10 = 1=1024 < 0:001), other sources of instrumental error are certainly at levels less that 5%. The approximately two dimensional behaviour is probably due to the regular inspi2 This

is not the case in gure 8.2, gure 8.3 gives an example of this behaviour

128

Chapter 8. Correlation dimension estimates

ration/expiration cycle along with breath to breath variation within that cycle. This is easily visualised as the orbit of a point around the surface of a torus. A dimension estimate of two could indicate that the attractor was any two dimensional surface, the embedded data however have an approximately toroidal or ribbon like shape (see gures 7.5 and 7.6). In this motion there is two characteristic cycles, rstly the motion around the centre of the torus or ribbon, and secondly a twisting motion around the surface. Our estimates slightly over two indicate that this behaviour is complicated further by some other roughness over the surface of the attractor. The shape of a toroidal attractor would very closely resemble the textured surface of a doughnut. A ribbon like attractor would consist of some portion of the surface of this doughnut.

8.3.2 Linear surrogates Dimension estimation has given information about the

shape of the dynamical system we are studying. In an attempt to classify this system we apply surrogate data techniques. First we compare breathing dynamics to linear systems. Following this, we compare the breathing dynamics to nonlinear dynamical systems by tting a type of nonlinear model to the data. By comparing the value of dimension obtained from our data and surrogates consistent with each of these three null hypotheses we were able to reject all three null hypotheses (see gure 8.5 for an example of such a calculation). These results are summarised in appendix A. Pilgram's [95] work with respiratory traces during REM sleep produced similar observations for a di erent physiological phenomenon. By rejecting these null hypotheses we may make two important observations. Firstly, the data are not a (monotonic) transformation of linearly ltered noise. And secondly, correlation dimension alone is sucient to distinguish between our data and data consistent with these hypotheses. These results, however comforting, are not particularly surprising. Our data are regular and periodic, and the surrogates are not (see, for example gure 8.6).

8.3.3 Cycle shued surrogates The dimension estimates for cycle shued

surrogates in gure 8.7 are typical of those produced by these surrogates. In almost all cases the dimension of the data was signi cantly lower than that of the surrogates. For 26 of our 27 data sets data and surrogate were signi cantly di erent for each of these linear hypotheses for at least one of de = 3; 4; 5. This would suggest that shuing the cycles has increased the dimension of the time series, replacing deterministic behaviour with stochastic. Figure 8.7 shows calculation of dimension estimates for such surrogates. There is a clear rejection of the hypothesis that there is no temporal correlation between cycles. Shuing the cycles produces surrogates that are often non-stationary and are distinguishable from cursory examination. We are unable to reject the hypothesis that the system is a noise driven (or chaotic) periodic orbit. In all our calculations the surrogate dimension estimates are highest when the surrogates are most non-stationary. The most

129

8.3. Results

Algorithm 0; 4 dimensional embedding 4

Algorithm 0; 5 dimensional embedding 4.5

4 3.5 3.5 3 3

2.5 −2

−1.5

−1

−0.5

2.5 −2

Algorithm 1; 4 dimensional embedding 4.5

−1.5

−1

−0.5

0

Algorithm 1; 5 dimensional embedding 5.5 5

4 4.5 3.5

4 3.5

3 3 2.5 −2.5

−2

−1.5

−1

−0.5

2.5 −2

Algorithm 2; 4 dimensional embedding 4

−1.5

−1

−0.5

Algorithm 2; 5 dimensional embedding 5 4.5

3.5 4 3.5 3 3 2.5 −2

−1.5

−1

−0.5

2.5 −2

−1.5

−1

−0.5

0

Figure 8.5: Linear surrogate calculations: An example of the surrogate data calculations for algorithm 0, 1 and 2. Here we compared the correlation dimension estimate for one of our data sets (solid line) and 30 surrogates (dotted lines). There is a clear di erence between the correlation dimension of the data and that of the surrogates.

130

Chapter 8. Correlation dimension estimates

Data 4 2 0 −2 0

20

40

60 Algorithm 0

80

100

120

20

40

60 Algorithm 1

80

100

120

20

40

60 Algorithm 2

80

100

120

20

40

60 Non−linear surrogate

80

100

120

20

40

60

80

100

120

4 2 0 −2 0 4 2 0 −2 0 4 2 0 −2 0 4 2 0 −2 0

Figure 8.6: Surrogate data: Sections of three surrogates generated by the traditional techniques | algorithms 0, 1 and 2 and a section of a surrogate data set generated from a cylindrical basis model. Also shown is a section of the real data used to generate these surrogates. There are obvious similarities between the true data and the nonlinear surrogate, whilst the other surrogates are obviously di erent.

131

8.3. Results

(normalised) dc

Shuffled at peaks 3

3.5

2.5

3

3.5 3

2

1.5 −2

2.5

−1

0

2 −2

2.5

−1

0

Shuffled at mid inspiration 3.5

3 (normalised) dc

4

2.5

2 −2

−1

0

−1

0

4 3.5

3

3 2

1.5 −2

2.5

−1

0

2 −2

2.5

−1

0

2 −2

(normalised) dc

Shuffled at troughs 3

3.5

2.5

3

4 3.5 3

2

1.5 −2 −1 0 Embedding dimension 3

2.5

2 −2 −1 0 Embedding dimension 4

2.5 2 −2 −1 0 Embedding dimension 5

Figure 8.7: Dimension estimates for cycle randomised surrogates: Surrogate data calculations for one of our data sets, embedded in R3 , R4 and R5 . The data set and representative surrogates are illustrated in gure 8.1. In each gure the solid line is the correlation dimension estimate for the data, whilst the dotted lines are estimates for 30 surrogates. The cuto scale log("0) is plotted against correlation dimension estimate dc ("0 ). Note that in each case the correlation dimension estimates are signi cantly higher for the surrogates | indicating an increase in complexity with cycle randomisation.

132

Chapter 8. Correlation dimension estimates

stationary surrogates appear reasonable to cursory inspection, but yield clearly distinct dimension estimates.

8.3.4 Nonlinear surrogates For each set of data we have calculated its corre-

lation dimension. Using a modelling algorithm described in chapter 6 we constructed a cylindrical basis model of the data. From this model we constructed 30 surrogate data sets. The surrogates were embedded in 2, 3, and 4 dimensions, using the same embedding strategy as the true data set. We then calculated the correlation dimension curve for each set of surrogate data. The results (see gure 8.8) of these calculations fell into two very distinct categories. For many of the data sets the surrogates very closely resembled the true dimension estimate whilst for some others the data and the surrogates appeared to be very di erent. Upon a closer examination of the time series, it appears that the model failed to produce accurate surrogates only when the data set was signi cantly non-stationary. Although no data set used in these calculations had an obvious drift or changed sleep state, nonstationarity occurred with sudden change in respiratory behaviour (see, for example, gure 8.3). Hence, when the data was suciently stationary (as was the case with 24 of our 27 data sets) the modelling algorithm produced surrogate data which were indistinguishable (according to the method of surrogate data, with respect to correlation dimension) from the true data. Furthermore, the models exhibited a toroidal or ribbon like attractor with small scale complex behaviour (stochastic or chaotic) consistent with the correlation dimension estimates. Even if both data and surrogate were stationary the dimension estimates of the surrogates could still be di erent from that of the data. In all these cases however this has been found to be a problem with the level of dynamic noise introduced to the model to generate the surrogates. By changing the noise level the dimension would also change, e ectively moving the dimension estimate vertically. Since, in these cases, the shape of the dimension estimate curves were approximately the same, by altering the noise level it was possible to produce surrogate estimates that were indistinguishable from the data. In all cases however, the dynamic noise was substantially less than the model's root mean square prediction error. The root mean square prediction error is the noise level predicted by the modelling algorithm. However this is the total noise and includes both dynamic and observational noise. Dynamic noise and observational noise have a di erent e ect on the correlation dimension estimates. Observational noise will increase the value of correlation dimension at length scales less than and equal to the noise level. It appears from our calculations that increasing the level of dynamic noise increases the correlation dimension estimate equally across all length scales | e ectively producing a vertical shift in the estimate. Increasing dynamic noise will certainly have a greater a ect on dc ("0 ) for larger "0 than a similar increase in observational noise would. Assuming one has correctly identi ed the

133

8.3. Results

Data set 1 2.2

3 2.4

2 2.2 2.5

1.8

2

1.6

1.8

1.4

1.6

1.2

1.4

1

−3

−2

−1

2

1.5

1.2 −3.5 −3 −2.5 −2 −1.5

−3

−2

−1

Data set 2 2.2

3 2.4

2 2.2 1.8

2.5

2 1.6 1.8

2

1.4 1.6 1.2

1.5 1.4

1

−3 −2 −1 2 dimensional embedding

−3 −2 −1 3 dimensional embedding

−3 −2 −1 4 dimensional embedding

Figure 8.8: Nonlinear surrogate dimension estimates: Surrogate data calculations for two of our data sets, embedded in 2, 3, and 4 dimensions. The rst set indicated a close agreement between data and surrogate. The second set of calculations indicated very clear distinction. Hence the model of the rst data set is indistinguishable (according to correlation dimension) from a noise driven periodic orbit, whilst the model of the second fails to produce particularly strong similarities. Notice that for almost any value of "0 , comparison of the value of dc ("0) of the data and the surrogates would also lead to these conclusions.

134

Chapter 8. Correlation dimension estimates

underlying deterministic dynamics, it may be possible to \tune" the level of dynamic noise so that surrogates and data have approximately the same value of correlation dimension estimates at moderate to large length scales, and then alter the level of observational noise to tune the dimension estimates at small length scales. Hence, the level of noise required to be unable to reject the surrogate data is an indication of the relative proportion of dynamic and observational noise in the system. That is, we can distinguish between random behaviour within the system (dynamic noise) and experimental error (observational noise).

8.4 Discussion This study has con rmed that apparently regular breathing during quiet sleep is possibly chaotic. This conclusion should be quali ed. Rapp [107] observation that to conclude that a phenomenon is chaotic is both dicult and often irrelevant is particularly signi cant here. In real data sets noise contamination will always increase the dimensional complexity of the data and almost any experimental data will exhibit non-integer correlation dimension. Identi cation of apparently chaotic behaviour is, however, a good rst step in dynamical analysis. We have extended our observations and analyses to describe the dynamical structure of the system in greater detail. Our dimension estimate results indicate that on a large scale there is low dimensional behaviour while the small scale behaviour was often dominated by very high dimensional dynamics or noise (that is, extremely high dimensional dynamics). Even though false nearest neighbour techniques suggest that we were embedding in high enough dimensions, there was still some small scale behaviour which lled the embedding space. The scale at which the embedding space is lled by the dynamics could indicate level of experimental noise. The most conclusive estimates from this study indicated that the structure of the attractor is likely to be similar to a torus or twisted ribbon with small scale, very high dimensional dynamics. Hence at large length scales the structure looked like the surface of a torus or ribbon whilst at smaller length scales dimension increased. This indicates that the attractor appears to be a torus with a very rough surface. The most important conclusion from these data is that this two dimensional, periodic system indicates two levels of periodicity. Hence, in addition to the periodic inspiration/expiration motion it is likely that there was some cyclic breath to breath variation. By applying the method of surrogate data we demonstrated that the correlation dimension is related to the data from which we estimate it in a nontrivial way. The surrogates produced by algorithms 0, 1, and 2 are clearly inadequate. It is apparent that they should fail and this was con rmed by our results. These simple surrogates con rm that our data are not generated by linearly ltered noise. Similarly the surrogates produced by shuing the cycles are di erent from the data. This produces a more substantial result; there is signi cant temporal correlation between cycles. We

8.4. Discussion

135

have constructed our own surrogates using a nonlinear modelling process and compared surrogates and data to test the accuracy of the model. For 24 of 27 data sets we found that the data and nonlinear surrogates were indistinguishable according to correlation dimension. For those data sets that were distinguishable from their surrogates, we found that there were several possible reasons for this. Usually, if the data was non-stationary the model simply failed to produce surrogates that were close enough to the data. The model is stationary and periodic, whilst the data is not. Occasionally, with non-stationary data the model failed to produce even periodic surrogates. If this was the case then the model had a stable xed point. In these cases the dimension estimates of data and surrogate were obviously di erent and a better model is required. The fact that this modelling algorithm failed in cases where the data were not stationary is not particularly surprising | both modelling and dimension estimation algorithms require stationarity. Perhaps with improved modelling techniques similar results could be obtained in these cases. In conclusion, the results of this chapter address the limitations of previous studies that have examined whether respiration is chaotic. We investigated children in quiet sleep when breathing appears most regular. Correlation dimension estimates are consistent with a chaotic system. Furthermore, unlike most previous studies, we used surrogate data analyses to test whether the apparently chaotic behaviour was due to linearly ltered noise. We found this unlikely and concluded that the simplest system consistent with our data is a noise driven nonlinear cylindrical basis model. Our data are the most convincing evidence that respiratory variability in infants is deterministic and not random, due to noise. A recent study has demonstrated reduced variability of respiratory movements in infants who subsequently died of sudden infant death syndrome (Schechtman [119]). This observation was retrospective but suggests that because the variability that we have observed during quiet breathing is deterministic, then further study using dynamical systems theory could allow early identi cation of infants at risk of SIDS from simple measurements of respiratory patterns.

136

Chapter 8. Correlation dimension estimates

CHAPTER 9

137

Reduced autoregressive modelling Chapter 8 demonstrates the possible existence of multiple oscillators within the respiratory system. In this chapter we utilise new linear modelling techniques which are an adaption of the nonlinear techniques of chapter 6 to detect cyclic amplitude modulation (CAM). Cyclic amplitude modulation is evidence of a second oscillator within the respiratory system. In chapter 10 we will discuss some more general nonlinear techniques that can be used to detect CAM type behaviour.

9.1 Introduction Periodic breathing is a familiar phenomenon that is not dicult to observe. It is characterised by periodic increases and decreases in tidal volume. Furthermore, the period of this periodic behaviour can be easily measured and remains relatively constant (see section 1.1.2, gure 1.2). During quiet sleep, however, it is often possible to observe that successive breaths uctuate almost periodically, in a way reminiscent of periodic breathing, but not nearly as pronounced and certainly not periodically apneaic (see gure 1.2 prior to the onset of periodic breathing). This phenomenon we will call cyclic amplitude modulation (CAM). The method we employ here extends the traditional autoregressive model of order n (AR(n)) which predicts the next value in a time series as a weighted average of the last n values. We consider instead a reduced autoregressive model (RARM) where any past values may be used to predict the upcoming value, but only those that are important are used. To determine which past values are important we employed Rissanen's minimum description length (MDL) criterion [110] (see section 2.3.2), using a modelling procedure originally described by Judd and Mees [62, 64]. In chapter 2 and 6 we outline this modelling procedure in the context of nonlinear radial (cylindrical) basis models our implementation of these methods for linear modelling has been presented elsewhere [133] (abstract), and will be discussed in future work [138]. A description of the mathematical methods is presented in a nonlinear context in section 2.3.3 and a linear application will be described in section 9.4. For now let us assume that RARM can produce a model consisting only of those previous values that are useful in predicting future values. This is not necessarily a particularly good model in terms of prediction | it is only an approximation to the breath to breath dynamics which we utilise to extract important information. We built reduced autoregressive models of tidal time series extracted from the original data. Successive elements of this tidal time series correspond to the magnitude of successive breaths. Using this information we deduce the period of approximately periodic behaviour in the time series from the temporal separation of the previous values. Hence RARM can identify the period of CAM in much the same way as autocorrelation may, except our methods prove to be more sensitive and more discriminatory.

138

Chapter 9. Reduced autoregressive modelling

By reducing the original data to a breath to breath time series we e ectively rescale the time axes so that each breath is of equal length. However, CAM on a breath to breath basis does not (necessarily) suppress time dependent dynamics. A hypothesised cyclic variation in breath duration may be related to a cyclic variation in breath amplitude (and hence evident in the breath amplitude time series). These could essentially be two separate observations of the same periodic behaviour. The \duration" of a single breath is also far more dicult to measure accurately due to (relatively) long at peaks and troughs. Other authors (see for example [11, 160]) have attempted to identify cyclic behaviour in breath sizes. Unlike previous methods which require careful measurement of respiratory parameters from a strip chart, our method is purely quantitative and completely automated. Furthermore, our method is applied to time series for which there is no obvious cyclic amplitude modulation. We will show that RARM algorithm can identify CAM when other methods, such as spectral analysis and estimates of autocorrelation do not. Fleming and others [34] have demonstrated cyclic oscillations in infants under 48 hours old during quiet sleep and after a sigh. In older infants the observed a decrease in this phenomenon. Some time ago Waggener and colleagues [12, 160] observed cyclic variation in high altitude ventilatory patterns of adult humans. They identi ed the period of cyclic variation by inspection of the strip chart and drew most of their conclusions from variation in the strength of the ventilatory oscillation. In [12] and another series of studies, Waggener and colleagues applied a comb lter [11] to detect periodicities. A comb lter is a series of band pass lters, which, e ectively act as a coarse approximation to the Fourier spectrum. Using this technique they demonstrated apparent ventilatory oscillations preceding apnea [162] and a link between apnea duration and ventilatory oscillations [164, 161]. However, no link between periodic oscillations (detected using a comb lter) and sudden infant death [163] was found. More recently Schechtman and others [119] identi ed signi cant di erences in the rst return plot of inter-breath times of sudden infant death syndrome (SIDS) victims and normal infants. Despite dramatically under-sampled data Schechtman demonstrated signi cant breath to breath variation. This chapter deals with the application of linear modelling techniques to detect and measure CAM. We introduce a new mathematical method of detecting periodicities based upon autoregressive modelling and the information theoretic work of Rissanen [110]. We compare this technique to the traditional autoregressive models and traditional methods of autocorrelation and spectral analysis. The data used in this study was collected at Princess Margaret Hospital for Children, the experimental protocol is described in section 1.2.

139

9.2. Tidal volume

9.2 Tidal volume In this section we will outline our data and pre-processing methods. In sections 9.3 and 9.4 we describe our mathematical techniques, and in section 9.5 we present some experimental results.

9.2.1 Subjects Using standard non-invasive inductance plethysmography tech-

niques (section 1.2) we obtained a measurement proportional to the cross sectional area of the chest or abdomen, which is a gauge of the lung volume. The present study collected measurements of the cross-sectional area of the abdomen of infants during natural sleep. From the data described in section 1.2.2 we examine 31 infants, studied at ages between 1 and 12 months. Seventeen of these infants where healthy (exhibited normal polysomnogram) and had been volunteered for this study. These infants are from group A. Fourteen children aged between 1 and 12 months, whom had been admitted to Princess Margaret Hospital for an overnight sleep study, were also studied. Eight of these subjects had been admitted to the hospital for clinical apnea, these are from the group B data. The remaining ve infants su ered from bronchopulmonary dysplasia (BPD), these are from group C.

9.2.2 Pre-processing The recorded time series represents the respiratory pat-

tern and from this we derived new time series, the successive elements of which represent the depth of successive breaths. To generate this time series we rst identi ed the value and location of the peaks and troughs in this time series. That is, peak inspiration and peak expiration (see gure 9.1). The peak and trough values were located by taking the most extreme value of the time series in a sliding window. Having selected the extremum from the time series it is possible to perform a quadratic or cubic spline interpolation. However, from our calculation this did not change the results signi cantly. From these time series of local extremum we determined the size of a given breath by calculating the di erence between the magnitude of each peak and the following trough. This di erence represents the total change in the cross sectional area over one exhalation. Hence, successive elements of this time series represent the tidal volume of successive breaths. Since inductance plethysmography measures cross sectional area, this new time series is actually \proportional" to change in the cross sectional area (and not lung volume). This \proportionality" is not constant. The undeveloped rib cage of infants is soft, and the relationship between abdominal area and lung volume may change with sleep state, sleep position and respiratory e ort. Furthermore it is not uncommon for infants to undergo paradoxical breathing, that is the rib and abdomen act 180 degrees out of phase. During data collection both rib and abdominal volume as well as air ow

140

Chapter 9. Reduced autoregressive modelling

Bs2t8 8 6 4 2 0 −2 −4 770

780

790

800

810

820 830 time (seconds)

840

850

860

870

850

860

870

Peak and trough values 8 6 4 2 0 −2 −4 770

780

790

800

810

820 830 time (seconds)

840

Breath size (peak value − trough value) 8 6 4 2 0 480

490

500

510 520 breath number

530

540

Figure 9.1: Derivation of the tidal volume time series: The circles are the points identi ed as peak inspiration and peak expiration. The second plot shows the peak and trough values as a function of time. It is from this that we extracted the tidal volume series | illustrated in the third graph. The horizontal axes in the third panel is the index of the breath size, whilst the other two panels are time: hence there is some horizontal shift between the second and third panel. This time series shows a section of irregular breathing and is not indicative of the data used in this study. It is used here for illustrative purposes.

141

9.3. Autoregressive modelling

through the mouth and nose (recorded with nasal and oral thermistors1) was recorded. From these it is possible to determine when paradoxical breathing occurred, all the recordings in this study occurred when rib and abdominal movement were in phase. Furthermore, EEG, EMG and EOG measurements were used to determine sleep state. The position of an infant remained constant during each recording. For the purposes of this study change in abdominal volume was used as an adequate representation of lung volume. An increase in lung volume will cause an increase in cross sectional area so that any periodic change in lung volume will cause a periodic change in cross sectional area. All analysis is of this derived \tidal volume" time series. In section 9.3 we apply standard autoregressive modelling techniques to detect CAM. However, surrogate tests will show that these methods are unreliable. Furthermore, this method is unable to estimate the period of CAM. In section 9.4 we describe the new RARM technique and section 9.5 describes some results from this method.

9.3 Autoregressive modelling For a scalar time series y1 ; y2; : : : ; yt one may apply a time delay embedding and assume a simple two dimensional model for the dynamics "

#

"

#

yt+1 = f yt : yt yt;1

Linearising f about the xed point (y0 ; y0) (where y0 = f (y0 ; y0)) we get that "

yt+1 yn

#

"

=

a b

#"

yt

yt;1

1 0

#

"

#

c ; + 0

(9.1)

@f j @f were a = @x (x;y)=(y0 ;y0 ) , b = @y j(x;y)=(y0 ;y0 ) , and c = (1 ; a ; b)y0. One can con rm that the xed point of (9.1) occurs at ( 1;(ca+b) ; 1;(ca+b) )T . Furthermore the eigenvalues of (9.1) are given by

1;2 =

1 2



p



a  a2 + 4b ;

(9.2)

and hence the stability of (9.1) is dependent on the value of (a2 + 4b) | see gure 9.2. By tting a model (9.1) to a scalar time series and examining the value of the parameters a and b one would hope to be able to infer the nature of the dynamics in the original time-series | i.e. if there exist periodic behaviour in the original time-series. In this section we perform some calculations to determine the reliability of estimates of a and b from a data set and conclude that this method has limited practical use for noisy data such as ours. However, these results do provide some evidence supporting CAM and motivate a closer examination of this phenomenon. 1 A temperature

sensitive electrode. Since exhaled air is warmer than room temperature this device give an indication of air ow.

142

Chapter 9. Reduced autoregressive modelling

b SN

SN

b = 1-a b = 1+a

S

S a

UN UN

(-2,-1)

(2,-1)

SF

SF UF

UF

2 a = -4b SN

SN a=-2

a=2

Figure 9.2: Stability diagram for equation (9.1): A plot in (a; b) space of the stability of the xed point of (9.1). The notation SN, UN, S, SF, UF denote regions were the xed point exhibits a stable node, unstable node, saddle, stable focus and unstable focus respectively. The diagram is symmetric about the b-axis. Evidently if a2 + 4b < 0 then the xed point exhibits a focus. This focus is stable if jaj < 2.

9.4. Reduced autoregressive modelling

143

9.3.1 Estimation of (a; b) Writing the eigenvalues (9.2) of the xed points of equation (9.1) as  i! one may ask how reliable are the estimates of and ! from

a data set. It is useful to compare the estimates of 1;2 (or simply the discriminant a2 + 4b) for data sets to algorithm 0 surrogates. Algorithm 1 and 2 surrogates do not produce signi cant results2 however, if the results of estimates of a and b for data are indistinguishable from algorithm 0 surrogates then this would indicate that our estimates of a and b are not signi cant. Figure 9.3 shows the distribution of values of (a2 + 4b) and b for algorithm 0 surrogates and a sample of 51 data sets derived from over 10 minutes of respiratory data recorded in the usual way. Data for this analysis is from all the groupings described in section 1.2.2. The results of gure 9.3 show that in the majority of data sets the estimates of a2 + 4b and a2 are indistinguishable from estimates of these quantities for i.i.d. noise. Hence, although the values of a2 + 4b and a2 for the data may suggest the presence of a stable focus these statistics would yield similar results if applied to i.i.d. noise. Furthermore, the variance of estimates of a2 + 4b and a2 is great, and therefore we require more satisfactory techniques of detecting CAM.

9.4 Reduced autoregressive modelling The essence of the new modelling method is to rst accurately and eciently express the tidal volume of the current breath as a linear combination (weighted average) of the tidal volumes of preceding breaths (on average). The best way to imagine this rst step is that the more preceding breaths one uses in a weighted average the more accurate the expression | but this is not ecient. To achieve eciency one would select fewer preceding breaths that more strongly in uence the present breath; this might be the immediately preceding breaths, but might also mean a breath 9 or 10 breaths ago if there were a strong periodicity. We use new mathematical methods drawn from information theory to determine which preceding breaths are most strongly in uencing the current breath. It is then a simple matter to look at the selected breaths to see periodicities. We deduce approximately periodic behaviour in the time series by identifying a strong similarity between the present breath size and previous breaths. If the present breath is most similar to those immediately preceding it we cannot deduce the presence of any periodic behaviour. However, if we can identify a signi cant similarity between this breath and one further in the past we can deduce the presence of some periodic behaviour in the data. In the same way we can use the autocorrelation function to detect periodic behaviour by observing a strong positive correlation between breaths. Although the Fourier spectral estimate is often used to identify periodic behaviour it is inappropriate to use this method for our data. Spectral estimation is good at 2 Algorithm

1 and 2 surrogates address the hypothesis that the system is linearly ltered noise, in tting the model (9.1) one assumes that the data are linearly ltered noise.

144

Chapter 9. Reduced autoregressive modelling

a2+4b

a/2 10

10

8

8

6

6

4

4

2

2

0

0

1

2 3 4 standard deviations

5

0

0

1

2 3 4 standard deviations

5

Figure 9.3: Surrogate data comparison of the estimates of (a2 +4b) and a2 from data to algorithm 0 surrogates: 51 data sets of tidal volume derived from respiratory recordings were used to estimate (a2 + 4b) and a2 . The value of these estimates was compared to algorithm 0 surrogates and the number of standard deviations between the two recorded. That is, for each data set we estimated (a2 + 4b) and a2 and calculated estimates of (a2 +4b) and a2 for algorithm 0 surrogates (data with the same rank distribution but no temporal correlation). Shown are plots of the distribution of the number of standard deviation between the value of these statistics for data and surrogates. Clearly the majority of these data sets are indistinguishable from noise. This demonstrates that the estimates of (a2 +4b) and a2 that we obtained from data are indistinct from estimates we would be likely to obtain from i.i.d. (independent and identically distributed) noise. Hence we cannot make any conclusion concerning dynamic correlations from estimates of (a2 + 4b) and a2 .

145

9.4. Reduced autoregressive modelling

identifying moderately high frequency behaviour, the periodicities we expect to identify are comparatively long period. To describe the reduced autoregressive modelling (RARM) algorithm we will rst discuss linear modelling. Following this we will describe an adaptation of the description length criteria of section 2.3.2 for linear models and our implementation of a model selection algorithm.

9.4.1 Autoregressive models The traditional autoregressive model of order n (an AR(n) model) attempts to model a time series fyt gNt=1 by nding the constants a1 ; a2; a3; : : : ; an such that

yt = a1 yt;1 + a2yt;2 + a3 yt;3 + : : : + anyt;n + et 8 t = n + 1; n + 2; : : : ; N: (9.3) where et is the model error. Methods for dealing with such models are well known [104, 155]. However, a time series exhibiting periodic behaviour with period  would have strong dependence of yt on yt; . Hence, by building an AR(n) model and determining which parameters are most signi cant it may be possible to estimate the period of some periodic behaviour or, more signi cantly, several di erent periods within the same series. Deciding which parameters are most \signi cant" requires sophisticated methods. To do so just on the basis of the size of the coecients ai ; i = 1; 2; 3; : : : ; n will rarely be useful. We discuss the selection problem in section 9.4.2. We wish to t the best model to the data. A traditional AR(n) model has n parameters but it may be the case that only some of these are necessary. Essentially then we are looking to nd the best model of the form

yt = a`1 yt;`1 + a`2 yt;`2 + a`3 yt;`3 + : : : + a`k yt;`k + et i = n + 1; n + 2; : : : ; N: where, 1  `1 < `2 < `3 < : : : < `k  n: `i 2 Z+ 8i 2 f1; 2; 3; : : : ; kg: That is, we only consider those parameters from equation (9.3) that are \signi cant", all others we set to zero. Since the data we consider does not have zero mean we will also allow for the possible selection of a constant term. For clarity we will also relabel the coecients and consider the model 8 >


or

for t = n + 1; n + 2; : : : ; N , where, 1  `1 < `2 < `3 < : : : < `k  n: `i 2 Z+ 8i 2 f1; 2; 3; : : : ; kg:

(9.4)

146

Chapter 9. Reduced autoregressive modelling

as before. The utility of setting some of the parameters to zero is that we are not over tting the data. If n  k then an AR(n) (or even an AR(`k )) model will have far more parameters than necessary, many of which will be tted to the noise of the system. Note that the coecients ai estimated in (9.4) are distinct from the corresponding coecients in (9.3). Some coecients of (9.3) are set to zero to obtain (9.4) but those remaining coecients in (9.4) must be reestimated. Indeed the value of these parameters will change upon reduction of the model (9.3) to a model of the form (9.4). To achieve this in a consistent and meaningful way it is necessary to test the signi cance of all parameters and determine which terms are not signi cant, and therefore which coecients may be set to zero. Using the concept of description length (section 2.3.2) we have a method of deciding which parameters o er a substantial improvement to the model. Rissanen's description length is just one way to compare the size of a model to its accuracy, other methods include the Schwarz [122] and Akaike [4] information criteria. Methods based on other measures of \signi cance" have been proposed by other authors, see for example [48] and the citations therein.

9.4.2 Description length Roughly speaking the description length of a particu-

lar model of a time series is proportional to the number of bytes of information required to reconstruct the original time series3 . That is, the compression of the data gained by describing the model parameters (a0; a1; a2; : : :ak ; `1; `2; : : : ; `k ; k) and the modelling prediction error (fetgNt=1 ). We discussed an application of description length to radial basis modelling in section 2.3.2. Obviously if the time series does not suit the class of models being considered then the most economical way to do this would be to simply transmit the data. If however, there is a model that ts the data well then it is better to describe the model to the receiver in addition to the (minor) deviations of the time series from that predicted from the model. Thus description length o ers a way to tell which model is most e ective. Our encoding of description length is identical to that outlined by Judd [62] and follows the ideas described by Rissanen [110]. For a model of the form (9.4) the description length will be given by (2.13), k

X L(zj^) + ( 12 + ln )k ; ln ^j :

j =1

The precisions j satisfy (2.12) (Q )j = 1=j where

Q = DL(aj^)  T =2 2 1 ;  e = D ; ln (2 2)n=2 3 To

within some arbitrary (possibly the machine) precision.

9.4. Reduced autoregressive modelling

147



 T   n n  = D 2 + 2 ln 2 n   = n2 D ln (B VB ; y )T (B VB ; y ) ;nVBT VB = (B VB ; y )T (B VB ; y )

can be easily calculated.

9.4.3 Analysis We apply this new mathematical modelling technique to identify

any approximately periodic behaviour present in the time series of breath size. To determine which model is best we apply the model selection algorithm of Judd [62] to the trivial case | the case in which only linear models are required. This algorithm was discussed in section 2.3.3 and it is exactly this algorithm we apply here. The set fVigmi=1 of candidate basis functions is constrained to contain only the linear terms. If

y V0 V1 V2

= = = = .. . Vj = .. . Vm = P

(ym+1 ; : : : ; yN )T ; (1; 1; : : : ; 1)T ; (ym ; : : : ; yN ;1)T ; (ym;1 ; : : : ; yN ;2)T ; (ym;j +1 ; : : : ; yN ;j )T ; (y1 ; : : : ; yN ;m )T :

then we build the best model y = i i V`i + , subject to minimising T  and select the model which minimises the description length (2.13). This new method is similar to identifying the extremum of the autocorrelation function. However, it is more sensitive and discriminatory. Our modelling method implicitly requires a parameter m, a maximum number of past values. To overcome this we examine the models produced for a variety of di erent maximum model sizes m (number of past values). The RARM procedure will produce a (possibly changing) indication of period as a function of maximum model size. We then look for the stage at which the previous breaths used to predict the next does not change by increasing the maximum model size. From this we deduce the period of any periodic behaviour. Figure 9.4 gives an illustration of such a calculation. From each such illustration we can list the periods detected along with the number of occurrences of each period. Using this information we deduce the period of any periodic behaviour present. From the calculations displayed in gure 9.4, for example, we can conclude that periodic behaviour exist over 5, 9 and 12 breaths. We can infer that the breathing is approximately periodic, with period

148

Chapter 9. Reduced autoregressive modelling

Spectral estimate

RARM algorithm 15

5

parameters

4444444444444444444444444444444444444444444444445 10

5

3333333333333333333333333333333333333333333333333333 3 5444 22222222222222222222222222222222222222222222222222222222 3

4 4555555555555555555555555555555555555555555555555554 111111111111111111111111111111111111111111111111111111111111 0 222333 0 20 40 60 model size

0 0

0.5 frequency (/breaths) Autocorrelation

1

10

40

1 0.5 0 0

20 lag

30

Figure 9.4: Reduced autoregressive modelling algorithm: Results of a calculation to detect periodic behaviour. The numbers indicate the order in which the parameters are selected, hence they are an indication of the relative importance of the parameters. Also shown is an estimate of the autocorrelation function and a spectral estimate using a 256 point overlapping (with 128 point overlap) Hanning window. Note the peak in the spectral estimate at approximately 0:35 breaths;1 this corresponds to periodicity over 2.8 breaths. The more important detail | over 5, 9 and 12 breaths according to the RAR model | is not evident in the spectral estimate. Periodic behaviour with period 5, 9 and 12 corresponds to a frequency of approximately 0:2, 0:11 and 0:083 breaths;1 . The autocorrelation function does, however have a peak at about 5 breaths and smaller peaks at 9 and 12 breaths. These peaks are not very pronounced and would be much harder to detect without the RARM results. This data set was selected as an example because the autocorrelation and the spectral estimate both have pronounced peaks. It is not representative of all our data sets: the spectral estimate and autocorrelation of most data sets have no pronounced peaks. 12. The presence of periodic behaviour over 5 and 9 breaths does not contradict this conclusion. These periods may represent sub-harmonics of the CAM, or (more likely) signi cant structure within the periodic waveform.

9.4.4 Data processing For each of the data sets we used the RARM technique

to determine the previous breath that most strongly in uences the current breath. We built RAR models for maximum model size ranging from 1 to 60. From these models we identi ed any long period time dependence within the data set, and deduce the likely period of approximately periodic behaviour. The autocorrelation function was also calculated and the extremum of this function are compared to the periodic behaviour detected by the RARM algorithm. Fourier spectral estimates proved to be of no help detecting these periodicities. To test the

149

9.5. Experimental results

signi cance of our results we applied three surrogate data tests (see chapter 3). For each data set we built 30 surrogates of each of the three linear types described by Theiler [152] (algorithm 0, 1, and 2) and applied our RARM algorithm to them. Applying algorithm 0 type surrogates is analogous to applying Theiler [151] cycle shued surrogates to the original time series (see section 3.3). Both surrogate generation algorithm destroy temporal correlation over more than one breath. The tidal volume time series removes a great deal of further information of the dynamics within a breath.

9.5 Experimental results In the following section we describe our results with RARM. We compare our RARM algorithm to the traditional autocorrelation function. We also verify our results using surrogate data calculations. We then use our algorithm to determine the existence of CAM during quiet (stage 3{4) sleep in 58 data sets from 27 infants. Following this we applied our RARM method to 102 data sets from 31 infants (irrespective of sleep state) and examine the relationship between CAM and apnea, and the nature of CAM before the onset of apnea. Data used in this study are from all groups described in section 1.2.2. A comparison of the results for groups A, B, and C is described latter in this section.

9.5.1 CAM detected using RARM In this section we present some prelimi-

nary results of the detection of CAM in the respiratory traces of infants in quiet sleep. The data used for these calculations are di erent from that for which the correlation dimension was calculated in chapter 8. The data requirements of this algorithm are moderately large (typically 10 minutes of recording), calculation of correlation dimension and radial (cylindrical) basis models for such data sets proved prohibitive. Moreover, the two types of models are entirely distinct: RARM is more robust to non-stationarity while cylindrical basis models are better at capturing qualitative (and many quantitative) features of respiration. Table 9.1 outlines the results of our calculations applied to 14 data sets from 14 infants. Data used for these calculations were recorded during quiet sleep. Subjects 1-10 are the same subjects as used for correlation dimension estimates of chapter 8. Data for subjects 1-6 were recorded during the same study as those used for dimension estimates. Data for subjects 7-12 were recorded at 4 months of age, for subjects 13-14 at six months. Respiratory rate is the average respiratory rate over the duration of the recording. Note that although there was some variability both in the respiratory rate and the period expressed as a number of breaths, the period in seconds is relatively constant. In most cases this period also falls within the range of periodic breathing. In subject 11 periodic breathing with cycle times from 13:5 to 15:5 seconds occurred during the same study.

150

Chapter 9. Reduced autoregressive modelling

subject

age (months)

1 2 3 4 5 6 7 8 9 10 11 12 13 14

2 2 2 2 2 3 4 4 4 4 4 4 6 6

respiratory rate (bpm) 20 37 24 26 48 27 25 32 22 22 24 23 22 21

CAM (breaths)

(seconds)

5 9 none 5 9 none 7 none 6 36 5 none 5 9

15 15 none 11 11 none 17 none 17 97 13 none 14 26

Table 9.1: Detection of CAM using RARM: The CAM detected by RARM for 14 data sets. The values are shown both in time and number of breaths.

9.5.2 RAR modelling results For each time series of breath size we computed

autocorrelation and Fourier spectral estimates. We applied our RARM algorithm to each data set and compared this to the result of applying traditional techniques. From this we obtained the following results. The period of periodic behaviour detected by the RAR algorithm is consistent with the periods detected by autocorrelation. That is, if RARM detects periodic behaviour, then it is of the same period as that detected by the autocorrelation estimate, if the autocorrelation detects periodic behaviour at all. Furthermore, if the RARM does not detect periodic behaviour, then neither does the autocorrelation estimate. Fourier spectral estimates was not able to detect CAM of a period greater than about three. The traditional techniques will often fail to detect periodic behaviour when the RARM algorithm does detect it. Furthermore, whenever periodic breathing, or visually obvious CAM respiratory motion occurred the period of this behaviour agrees with the period predicted by the RARM algorithm and by the traditional techniques, if the spectral estimation or autocorrelation techniques detect anything. The results of the RARM process almost always agree with one of the largest extremum of the autocorrelation function. However traditional techniques alone rarely indicate a clear periodicity. Detection of periodic behaviour with our RARM algorithm is an indication of CAM. In our data CAM was detected by RARM in 49 of our 102 datasets (28 of 58 in quiet

9.5. Experimental results

151

A: Volunteers Subject

Data Length Age Resp. Apnea CAM set (seconds) Rate. (bpm) (breaths) (seconds) subjectA As4t1 693 6 24.19 no 15 37 subjectA As4t2 2402 6 20.41 yes 10 26 29 76 subjectBb Bs2t8 951 2 37.97 yes 5 28 8 45 subjectBb Bs3t5 489 4 23.81 no 15 38 subjectG Gs3t3 1647 4 29.41 no 9 18 subjectJ Js3t4 916 4 47.62 yes 9 11 subjectJ Js4t4 1122 6 32.26 yes 34 6 63 11 subjectL Ls3t2 1174 4 34.09 no 68 11 14 subjectM Ms3t3 1700 4 27.03 yes 7 27 16 60 subjectN Ns3t4 509 4 26.79 no 23 52 subjectR Rs2t4 1357 2 35.71 yes 8 13

Table 9.2: continued on next page. sleep). The period of the CAM detected by RARM in quiet sleep is summarised in table 9.2. The respiratory rate given in this table is the average rate of respiration over the time of the recording. Applying standard statistical tests at the 95% con dence level we found no signi cant statistical link between sleep state and the occurrence or period of CAM. Similarly we found that there is no signi cant link between occurrence of apnea and the period of CAM detected by RARM, nor is there any statistically signi cant link between the period of CAM and the subject groupings. We consider the possibility of statistical links between CAM, apnea and the subject groupings in section 9.5.4.

9.5.3 Veri cation of RARM algorithm with surrogate analysis By com-

paring our results to results obtained from surrogate data we determined that our algorithm was behaving as expected. When we compare our data to surrogates generated by shuing the data (algorithm 0) we would expect any CAM detected in the data to not be present in the surrogates. Whereas surrogates generated by algorithm 1 and 2 are expected to be similar to the data. Both surrogate generation and RARM rely on identifying the linear system that is the most likely source of our data. Therefore, both methods should identify the same linear system. In all our surrogate calculations algorithm 0 failed to produce surrogates suciently similar to the data, whilst algorithm 1 and 2 succeeded in generating surrogates apparently from the same class of linear phenomena. Hence this RARM procedure provides a superior test of CAM to the AR(2) statistics of section 9.3. Figure 9.5 gives a representative example of such a calculation.

9.5.4 Prevalence of CAM and apnea Table 9.3 shows a summary of our obser-

vation of the incidence of CAM and apnea in subjects from each of our three groupings.

152

Chapter 9. Reduced autoregressive modelling

B: Subjects admitted with pronounced apnea Subject

Helena Tessa Tessa Jarred Jarred Jarred Jarred Alexander Alexander Morgan Morgan Morgan DavidM

Data Length Age Resp. Apnea set (seconds) Rate. (bpm) Helena1 7078 9 26.55 yes Tessa1 1412 4 29.41 yes Tessa8 1560 4 27.27 yes Jarred1 960 3 66.67 no Jarred4 877 3 63.83 no Jarred5 2779 3 63.83 no Jarred7 2315 3 65.22 no Alex1 1063 5 26.55 yes Alex2 1624 5 27.78 yes Morgan1 29603 10 31.25 yes Morgan3 67046 10 30.93 yes Morgan4 56565 10 29.13 no DavidM2 47042 6 27.27 no

CAM

(breaths)

(seconds)

11 16 13 18 16 8 7 12 21 11 19 4 20 12 50 39 26 10 27 47 6

25 36 26 40 14 8 7 11 20 10 17 9 45 26 108 75 50 20 4 14 8 14 13

C: Subjects admitted with BPD Subject

Data Length Age Resp. Apnea CAM set (seconds) Rate. (bpm) (breaths) (seconds) Joel Joel5 1345 8 29.7 yes 46 8 12 Kristopher Kris8 47124 4 34.09 no 8 38 25 33 33 23 8 5 Andrew Andrew3 99848 9 29.7 yes 65 50 6 Andrew Andrew7 55845 9 26.55 yes 532 53 3 2

Table 9.2: Results of the calculations to detect periodicities: The main period, or periods of any behaviour detected is shown as a number of breaths. The periods noted on this table are those most frequently used to build the RAR model (over models size m from 1 to 60). Only periods greater than 2 are recorded. All recordings are of infants in quiet sleep. The duration of the recording, and the respiratory rate for each data set is also recorded. Results are shown only for the time series in which CAM was detected | slightly under half of all our data.

153

9.5. Experimental results

Algorithm0 parameters

60 40 20 0

5

10

15 surrogate Algorithm1

20

25

30

5

10

15 surrogate Algorithm2

20

25

30

5

10

15 surrogate

20

25

30

parameters

10

5

0

parameters

10

5

0

Figure 9.5: The surrogate data calculation for one data set: For algorithms 0, 1, and 2, 30 surrogate data sets were calculated and the period of periodic behaviour determined using the RARM algorithm. The 30 surrogate data sets are shown horizontally (there is no temporal horizontal ordering), the result of applying our RARM algorithm are shown vertically. The parameters selected by RARM (which imply CAM of the same period is shown on the vertical axis for each surrogate). According to the RARM algorithm the true data set had periodic behaviour over 7 and 8 breaths. Algorithm 0 never produces this behaviour. Algorithm 1 predicts this behaviour in 27 of 30 surrogate data sets (the remaining 3 indicate periodic behaviour over only 8 breaths). Algorithm 2 surrogates have CAM over 7 and 8 breaths in 16 of 30 surrogates, the remaining 14 have no periodic behaviour (period 1).

154

Chapter 9. Reduced autoregressive modelling

subjects (total number)

data sets apnea (number)

total 0.57 0.40 0.64 0.55y 0.86z 0.55x

CAM during apnea otherwise 0.41 0.40 0.52 0.58x 0.58y 0.33

A: volunteers 17 47 B: apnea 9 33 C: BPD 5 22 Table 9.3: Prevalence of CAM and apnea: The data observed from all subjects

have been divided into two categories, non apneaic subjects and those exhibiting apnea. For each data set we observe the presence or absence of both CAM and apnea (de ned 3 minutes,  to be movement of not more than 0:2   for at least RR RR is the mean respiratory rate). Using a binomial distribution the probability p that the fractions x, y and z are generated by the same random variable as the corresponding result for group A satis es p < 0:18, p < 0:10 and p < 0:05 respectively. All other values in the table have a lower signi cance. We detected apnea in the data by looking for variation of no more than 0.2 (where 3 (where   denotes the standard deviation of the data) for a duration of RR RR is the average respiratory rate). From our relatively limited data it appears likely that infants su ering from BPD are more likely to exhibit CAM during apneaic episodes than their normal counter parts. Apneaic infants have a higher incidence of CAM, the level of signi cance associated with these results are not great. However, if the estimated proportions are accurate then we would not expect a greater signi cance for this limited quantity of data.

9.5.5 Pre-apnea periodicities An increase in CAM before onset of apnea can

commonly be observed by eye. In two of our subjects from group A we observed periodic breathing following a large sigh and a short pause in eupnea. In data sets from both these infants we observed CAM during quiet sleep of approximately the same period as the periodic breathing (see gure 9.6). A further ve time series from four other infants exhibited marked CAM following a sigh. We were able to measure this directly and we compared the period of this behaviour to the period of CAM detected by RARM in a sample of quiet sleep recorded from the same infant during the same session. The period of these behaviours agreed closely and are summarised in table 9.4. Furthermore, by building complex nonlinear models described in chapter 8.2 we were able to observe CAM in arti cial data generated from such models built from a short section of data from directly before the onset of periodic breathing. Results of these calculations are presented in table 6.2 (section 6.3.3). Such models may prove helpful in further analysis of breath to breath respiratory variation.

155

0 −2 −4 0

50

100 150 time (sec)

200

Abdominal movement

2

6 4 2 0 −2 −4 0 10

6

peak−trough

peak−trough

Abdominal movement

9.5. Experimental results

4 2

50

100 150 time (sec)

200

5

0 0

50 breath (number)

100

0

50 breath (number)

100

Figure 9.6: Pre-apnea periodicities: The top two plots illustrate sections of respiratory data taken from the same subject (1 month old male). The left hand data set was recorded 25 minutes before the right, and both are 240 seconds in length. The bottom two plots are the corresponding breath size time series for the same data. This rst recording exhibited CAM detected using RARM of between 13.3 and 15.6 seconds. The second data set exhibited periodic breathing with cycle times between 13.5 and 15.5 seconds.

156

Chapter 9. Reduced autoregressive modelling

subject subjectA subjectBb subjectBb subjectG subjectH subjectM subjectR

CAM detected time data set by RARM elapsed data set (before) (breaths) (seconds) (minutes) (after) As4t1 15 37 25 As4t2 Bs2t8 5 8 0 Bs2t8 Bs3t5 4 10 ;100 Bs3t1 Gs2t1 5 9 15 Gs2t4 Hs1t1 9 10 5 Hs1t2 Ms1t4 6 13 25 Ms1t6 Rs2t2 6 8 20 Rs2t4

CAM after sigh (breaths)

5 6 5 5 9 5 8

(seconds)

25 9 10 9 13 14.5 16

Table 9.4: CAM after sigh and RARM: Comparison of CAM after sigh (apparent to visual inspection), the second set of results, and CAM detected using RARM, the rst set of results. Data sets Ms1t6 and Bs2t8 exhibited periodic breathing. The elapsed time is the time between the measurements; a negative value indicates that the second recording was made rst, zero indicates that the second recording commenced immediately after the end of the rst. Table 6.2 compared the detection of CAM in model simulations to that evident letter in the recording. This table compares the detection of CAM in data before and after sigh. The data sets with visually evident CAM are the same as in table 6.2, the data sets of quiet respiration are di erent. Data for these calculations are from group A (section 1.2.2).

157

9.6. Conclusion

9.6 Conclusion Standard autoregressive techniques and stability analysis of AR(2) models were shown to not be useful. After comparing RARM to autocorrelation and Fourier spectral estimates we conclude that this new method is more sensitive than traditional techniques, whilst being more decisive. Traditional techniques tend to be produce broader,

atter peaks. The RARM process will, by virtue of the description length criteria, select precise values (see gure 9.4). Notice that in the case of gure 9.4, the autocorrelation does have local maximum values at the same point as that predicted by the RAR model; the precise value is less certain. The spectral estimate also detects similar peaks in the same regions. However, spectral estimation is more sensitive to high frequency activity than it is to lower frequencies which we are trying to detect. In many cases these results identify more than one period of behaviour. This may be for several reasons. The behaviour may not be exactly periodic, or the RARM process may by building a model which involves harmonics or sub-harmonics. These harmonics and sub-harmonics are detected in much the same way as spectral analysis often shows more than one peak in a periodic data set. For example, data set Jarred5 yields a RAR model with lags of 7, 12, and 21. This probably indicates periodic behaviour over about 12 or 21 breaths. Note that these values are approximately multiples of one another, it is dicult to tell which is the period and which is the harmonic, or sub-harmonic. The observation of CAM is intriguing. We serendipitously recorded periodic breathing from one infant. The cycle time of CAM (13:3{15:6 seconds) in the same infant corresponded almost exactly with that of the observed periodic breathing (13:5{15:5 seconds) as demonstrated in gure 8.3. The relationship to periodic breathing needs further investigation, but we believe that these two behaviours with identical cycle lengths (CAM and periodic breathing) are likely to be related and determined by similar factors whatever they might be. These data support the hypothesis that oscillatory activity responsible for periodic breathing is ubiquitously present but masked during apparently regular breathing by the regular stimulation from respiratory motor neurons4 . Periodic breathing occurs when this normal regular drive is decreased (for example, in infants when core body temperature is raised) [59]. The adoption of one particular physiological state, regular tonic respiration with CAM or periodic breathing, is likely to be dependent upon the environmental conditions and maturity of respiratory control as well as the presence of any pathological conditions. Ours are the rst convincing 4 The

observation of CAM is consistent with the regular stimulation of the respiratory system from respiratory motor neurons. This would imply that the respiratory system is a forced system. However the modelling techniques we utilise in this thesis (chapter 6) are autonomous. These two distinct types of systems are not, however, mutually exclusive. The autonomous system model we construct is a model of the whole respiratory system (including, if necessary, ring of respiratory motor neurons) and so includes any necessary periodic forcing within the system as a regular driving force. Our nonlinear models are able to mimic the respiratory system well, and these models are therefore capable of emulating the necessary neurophysiological driving force for human respiration.

158

Chapter 9. Reduced autoregressive modelling

data to support such a hypothesis. Furthermore, it is possible that multiple periods detected by RARM may indicate more than one period of behaviour. It is also possible that shorter lags may indicate the presence of substantial structure within the periodic cycle. For almost all of the data sets for which periodic behaviour is observed some component of this behaviour is present over 10{20 seconds, for most data sets this range is even narrower, perhaps 13{17 seconds. Note that this behaviour is almost independent of the respiratory rate. After calculating RAR models we generated surrogates and compare the models produced by the surrogate data to that produced by the original time series. We found that, as expected, algorithm 0 surrogates produced RAR models dissimilar from that of the original data. Algorithm 1 and 2 performed better producing a close agreement with the data. However, algorithm 1 produced surrogates that more closely resembled the data than algorithm 2. We believe this to be because algorithm 2 represents a larger class of linear functions and so, fewer of the surrogates are suciently similar to the data. This demonstrates that the RARM algorithm produces superior statistics to the parameters of AR(2) models. Algorithm 1 surrogates are all forms of linearly ltered noise, that is noise driven ARMA (autoregressive/moving average) processes. Our RARM algorithm builds a model of this form and so can detect ARMA process very well. Algorithm 2 surrogates represent a (monotonic) nonlinear transformation of ARMA process. This nonlinear transformation can produce surrogates suciently dissimilar from our data that the RARM algorithm identi es a di erent type of behaviour. This may indicate that a linear model does not suciently model every aspect of the system generating the data | a more complicated (possibly nonlinear) model is required. Another explanation for this is o ered by Schreiber and Schmitz [121]: algorithm 2 surrogates will not have exactly the same Fourier spectrum as the data, these small di erences between Fourier spectra (and hence autocorrelation) may be signi cant enough for the RARM algorithm. Based on our own calculations we believe it is more likely that a monotonic nonlinear transformation changes the estimate of the RARM parameters suciently and that the concerns raised by Schreiber and Schmitz are less signi cant [137] (see chapter 4). Our surrogate calculations lead us to conclude that there is some time dependent structure in the data. Our linear (RAR) models are a good method to identify the general nature of this structure, but, are insucient to describe completely the behaviour of the system responsible for our data. Complex nonlinear models such as those described in chapters 2 and 6 would o er a more accurate description of the dynamics of respiration. In chapter 10 we describe a more complex nonlinear analysis on CAM. Our data suggest a possible link between CAM and clinical apnea. However, our results are preliminary and we would need many more data sets to produce results which are statistically meaningful.

9.6. Conclusion

159

We speculate that since CAM is an important contributor to the complexity observed during quiet breathing, further studies might demonstrate distinct patterns of CAM in infants with respiratory control problems for example, absence of CAM might explain the reduction in variability observed by Schechtman [119] in infants who died of SIDS. Finally our results suggest that the period of periodic breathing is the same as CAM detected in quiet sleep by RARM algorithm.

160

Chapter 9. Reduced autoregressive modelling

CHAPTER 10

161

Quasi-periodic dynamics Chapter 9 demonstrates the existence of cyclic amplitude modulation (CAM) in the amplitude of infant respiration. However, the analysis of chapter 9 o ers only a linear approximation to that behaviour. In a previous chapter (section 7.3) we presented some preliminary attempts at an analysis of qualitative features of this behaviour. In this chapter we will introduce two useful tools for a more quantitative analysis of that same phenomenon. Namely, Floquet theory [47] and analysis of Poincare sections (the rst return map) [65]. Both of these techniques utilise nonlinear models described in chapter 6, dynamic properties of the models are calculated, it is inferred that the original system has the same properties. All the data used in this chapter are from group A (section 1.2.2). There is some evidence in the physiological literature to support such an approach. In their analysis of respiration in rats, Sammon and Bruce [118] demonstrated substantial structure in the rst return maps. In particular, they showed that models of respiration exhibit parabolic rst return plots supporting the existence of a period doubling bifurcation. Finley and Nugent [29] describe an analysis of Fourier transformation which support the presence of a low frequency periodic component approximately equation to periodic breathing during normal respiration. A arimaa and Valimaki [1] have shown a stronger high frequency component in healthy term infants compared to healthy pre-term. By analysing the rst return plots for breath to breath intervals Schechtman and colleagues [119] showed reduced variability of respiratory movements in infants who subsequently died of sudden infant death syndrome. This study utilised a particularly large sample of infants, unfortunately the data recording methods produced dramatically under sampled results. Despite this, the results were fairly conclusive. With measurements from strip charts Waggener and colleagues [160] demonstrate the presence of a similar CAM mechanism in human adults at extreme altitude. Using a comb lter [162, 164, 161] the observe some oscillatory behaviour in infants before apnea. Unlike these studies we utilise nonlinear models of data and do not use the data directly. In this chapter we will apply the techniques of Floquet theory and Poincare sections to determine the presence and nature of nonlinear mechanism in models of infant respiration.

10.1 Floquet theory From a data set we can build a map F of the dynamics of respiration. That is, the map F approximates the dynamics of the hypothesised underlying dynamical system over a short, xed time span. Let z be a point on a periodic orbit of period p, that is

z = F p (z ) = F|  F {z  : : :  F}(z): p times

162

Chapter 10. Quasi-periodic dynamics

Hence z is a xed point of the map F p and we can calculate the eigenvectors and eigenvalues of that xed point. These eigenvectors and eigenvalues correspond exactly to the linearised dynamics of the periodic orbit: one eigenvector will be in the direction DF (z ) and will have associated eigenvalue 1, the others will be determined by the dynamics [47]. To calculate these eigenvectors and eigenvalues we must rst linearise F p at z. We have that

Dz F p (z) = DF p;1 (z) F (F p;1(z))Dz F p;1(z) = DF p;1 (z) F (F p;1 (z ))DF p;2 (z) F (F p;2 (z )) : : :Dz F (z ) =

pY ;1

k=0

DF k (z) F (F k (z)):

(10.1)

One may then calculate the eigenvalues of the matrix pk;=01 DF k (z) F (F k (z )) to determine the stability of the periodic orbit of z . Unfortunately the application of this method has several problems. To calculate (10.1) one must rst be able to identify a point z on a periodic orbit. In practice a model built by the methods described in chapter 6 will typically have been embedded in approximately 20 dimensional space. In this situation, we limit ourselves to the study of stable periodic orbits. Fortunately this is a common feature of these models. However, a supposed periodic orbit may not, in fact be strictly periodic. The map F is a discrete approximation to the dynamics of a continuous system and it is unlikely that the \periodic orbit" of interest will be periodic with exactly period p | the period will be of the order of the embedding dimension (see chapter 5). In most cases it is only possible to nd a point z of an approximately periodic orbit. By this we mean that z and F p (z ) are close. If the map F is not chaotic then one can choose a point z such that fF p (z )g1 p=1 is bounded and p will be chosen to be the rst local p minimum of kF (z ) ; z k for p > 1. Having found a point z such that fz; F (z ); F 2(z ); : : : ; F p;1 (z )g form points of an \almost periodic" orbit the expression (10.1) may be evaluated. However since p is approximately 20 and the periodic orbit fz; F (z ); F 2(z ); : : : ; F p;1 (z )g is (presumably) stable the calculation of the eigenvalues of (10.1) will be numerically highly sensitive. Q The eigenvalues will be close to zero and the matrix pk;=01 DF k (z) F (F k (z )) will be nearly singular. By embedding the data in a lower dimension (perhaps not using a variable embedding strategy) this calculation becomes more stable. However, as the Q calculation of pk;=01 DF k (z) F (F k (z )) becomes more stable the periodic orbit itself will be more \approximate", and the model will possibly provide a worse t of the data. Figure 10.1 demonstrates some of the common features of models with a low embedding dimension. Models that predict a short time (less than 14 (approximate period)) ahead by only using the immediately preceding values provide a poor t of the data. However if we embed using a uniform embedding strategy such as (yt ; yt; ; yt;2 ), where   1 (approximate period) we can build a model y t+1 = f (yt ; yt; ; yt;2 ). However, it is 4 Q

163

10.1. Floquet theory

3 2 1 0 −1 50

100

150

200

3 2 1 0 −1 −1

250

x3

x3

−2 0

0

1

2 x1

3

1 −1 0 x2

2

3

300

350

400

450

500

3 2 1 0 −1 −1

0

1

2 x1

3

1 −1 0 x2

2

3

Figure 10.1: Free run prediction from a model with uniform embedding: The top plot shows a free run prediction of a model yt+ = f (yt ; yt; ; yt;2 ) where  is the closest integer to 14 (approximate period) of the data. The bottom two panels show an embedding (x1; x2; x3) = (yt ; yt; ; yt;2 ) of that free run prediction. The plot on the left shows that the free run prediction is not periodic, the one on the right demonstrates that it does have a bounded 1 dimensional attractor. The problem with this model is that the approximate period of the model and 4 do not agree precisely.

164

Chapter 10. Quasi-periodic dynamics

impossible to iterate a model of this form to produce a free run prediction. Models of the form yt+ = f (yt ; yt; ; yt;2 ) are not likely to produce periodic orbits as it is unlikely that the relationship 4 = (approximate period of data) will hold exactly. For a given embedding lag  and embedding dimension d determined by the methods discussed in chapters 2 and 6, we have applied this technique to two types of models. The rst type of model is those with cylindrical basis functions and the embedding strategies described in chapter 6 (e ectively producing periodic orbits with period d ). The second are models with only a uniform embedding strategy with constant lag  to predict  points into the future (producing periodic orbits with periods of approximately d). We Q expect that the rst type of model will produce matrices pk;=01 Dz F (F k (z )) that are close to singular, the second approach will produce short periodic orbits and an inferior model of the dynamics of the data. As expected, the second type of models (those with a uniform embedding) produce non periodic behaviour. Therefore, we did not use these models. From models built with a nonuniform embedding we calculate the eigenvalues and eigenvectors of the periodic orbits. The results of these calculations are summarised in appendix B, table B.1. Most (35 of 38) of these models produces complex eigenvalues with absolute value less than one. This indicates that the map F p has a stable focus, or that trajectories will spiral towards the periodic orbit. This provide additional evidence for the presence Q of CAM. However, the shortcomings of these calculation of pk;=01 DF k (z) F (F k (z )) or approximation of the periodic orbit for low values of p limit the signi cance of these results somewhat.

10.2 Poincare sections In this section we redress some of the limitations of the previous section by using a more qualitative approach to the same problem. The method of Poincare sections, or rst return maps is a widely applied tool in the study of nonlinear dynamics [65]. In general one makes a plot of successive intersections of a ow  in d dimensions with a d ; 1 dimensional hyper plane (generally normal to r, the time derivative of ). For d = 2 this is particularly easy. If zt and zt+p are successive intersections of a ow  with the hyper plane (line) ; one can calculate the projections of zt and zt+p onto ; and plot proj; zt against proj; zt+p in 2 dimensions. If zt is a periodic orbit of  then zt = zt+p so there is a xed point at proj; zt . However, if d > 2 the situation becomes slightly more complex as the plot of proj; zt against proj; zt+p will be in R2d;2 . For cylindrical basis models with d  201 the situation is substantially more complex. However, in a manner analogous to the approach of section 7.3 we can examine the deformation of a rectangular hyper prism in Rd ;1 | or at least the deformation of a projection of that prism into R3 . 1 Typically, d

is of the order of the period of the data. Table B.1 includes typical values of the length of one orbit of the map.

10.2. Poincare sections

165

Figure 10.2: Iterates of the Poincare section: The points represent successive iterates of the intersection of the data with the hyper surface yt;15 = constant. The embedding used is (yt ; yt;5; yt;10). Note that the points converge to a 1 dimensional subset of the embedding space. Hence the attractor is contained in this 1 dimensional subset | either it is a xed point or a section of the curve. The three axes show the location of the coordinate axes over the range [;1; 1]. The corresponding URL is http://maths.uwa.edu.au/watchman/thesis/vrml/Poincare.iv.

166

Chapter 10. Quasi-periodic dynamics

Figure 10.3: First return map for a large neighbourhood: The frame of a rectangular prism is the neighbourhood of a xed point of the Poincare section of the ow approximated by a model of the data shown in gure 6.1. The distorted shape is the next intersection of points on that prism with the hyper surface yt;15 = constant. The embedding used is (yt ; yt;5; yt;10). To provide a sense of scale the (quasi-)periodic orbit of a free run iteration of this model is also shown. Each side of the prism is coloured the same in the distorted next intersections as it is in the initial shape, however grey scaling obscures much of the detail. The corresponding (colour) computer le is located at http://maths.uwa.edu.au/watchman/thesis/vrml/firstreturn1.iv.

10.2. Poincare sections

167

Figure 10.4: First return map for a small neighbourhood: The frame of a rectangular prism is an immediate neighbourhood of a xed point of the Poincare section of the ow approximated by a model of the data shown in gure 6.1. The small dark curve is the next intersection of points on that prism with the hyper surface yt;15 = constant. The embedding used is (yt ; yt;5; yt;10). To provide a sense of scale the (quasi-)periodic orbit of a free run iteration of this model is also shown. The corresponding computer le can be obtained from the URL http://maths.uwa.edu.au/watchman/thesis/vrml/firstreturn2.iv.

168

Chapter 10. Quasi-periodic dynamics

Unfortunately the global embedding we use to build these models is approximately 20 dimensional, and generating sucient points on such a surface is computational intensive. Instead of examining the projection of a deformation of that prism we are forced to work with the deformation of a projection of that prism into R3 . E ectively we look at a set of points on the prism in Rd ;1 and on a 3 dimensional surface in Rd ;1 . The particular three dimensional surface we choose is determined by the embedding coordinates we view, but also by the dynamics of the data. Three of the coordinates correspond to points on the surface of this prism, one is determined by the Poincare section we choose, the remaining d ; 4 coordinates are determined so that the points in Rd are \close" to the data. The could be done as a complex minimisation problem, we choose to apply a form of linear interpolation. In this way each point of the prism corresponds to a point in Rd which is the time delay embedding of a set of d point in R which represent an \arti cial" (but \realistic") breath. Figure 10.2 shows the general structure of the attracting set of the rst return map. The data point converge to a 1 dimensional curve after about 2 iterations of the rst return map. This indicates the presence of either a stable xed point, a periodic/quasiperiodic orbit, or chaotic behaviour. All models of all data sets which we have examined in this way exhibit a similar 1 dimensional attracting set (either containing a xed point, or a periodic, quasi-periodic or chaotic limit set). Figure 10.3 and gure 10.4 are not so clear. These gures are grey scale representations of 3 dimensional coloured structures and much of the detail is obscured by these illustrations. The prism illustrated is the bounding box of the rst intersection of the data with the hyper surface yt;15 = (constant) in R16. However, one can see from gure 10.3 that there is a substantial amount of nonlinearity in the rst return map. In this manner it is possible to identify the attractor of the rst return map: starting with the data, iterate the rst return map until the size (diagonal length) of the bounding box of the intersection of the data with the Poincare section does not decrease, successive iteration of the map will eventually cover the attractor. In gure 10.4 the prism is the second intersection of the data with the same hyper surface. Figure 10.4 clearly shows the nature of the limiting behaviour of the rst return map, the initial points are projected onto a 1 dimensional set. Note the intersection of this one dimensional set with the limit cycle, successive iterations of the rst return map cause that 1 dimensional set to shrink onto the limit cycle. Also note that the right hand end of the rectangular prism maps to the left hand end of the attractor. This indicates a stable focus in the rst return map.

10.3 Remarks Many of the results of this chapter are preliminary. However, the estimates of eigenvalues of the \periodic orbit" using Floquet theory clearly present substantial evidence for a stable focus like structure | at least on a 2 dimensional set. Furthermore, qualita-

10.3. Remarks

169

tive analysis of a rst return map of these models yield similar results. The application of these methods is somewhat limited due to the high dimensional nature of the map. Even with a 3 dimensional viewer one can only examining a very few aspects of the rst return map. These methods do show that the rst return map of models of infant respiration very quickly converges to a curved 1 dimensional set, this set is evidence of either a xed point in the rst return map, a periodic or quasi-periodic orbit or a chaotic rst return map. If a xed point exists then its eigenvalues are likely to complex and so it is a stable focus. If the rst return map exhibits either a stable focus or a (quasi-)periodic orbit then the observation of CAM in chapter 9 is to be expected and appears to be ubiquitous.

170

Chapter 10. Quasi-periodic dynamics

171

Part IV

Conclusion

CHAPTER 11

173

Conclusion This thesis describes an application of existing and new methods within the eld of dynamical systems theory to the analysis of human infant respiratory patterns during sleep. We have show that the respiratory system of human infants is not a linear system and exhibits two or three degrees of freedom (chapter 8). The complexity of this system is augmented by small scale high dimensional behaviour. The scale of this behaviour is distinct from instrumentation noise due to digitisation of a continuous analogue signal. Observed high dimensional behaviour is therefore due to the complex interaction within the respiratory system and with other physiological processes. We show that cyclic amplitude modulation (CAM) may be observed directly from recordings of respiratory movement during quiet sleep (chapter 9). Cyclic uctuations in amplitude are also present in free run predictions of nonlinear models tted to respiratory recordings (section 6.3.3). Dynamic analysis1 of these models have provided further evidence of CAM. We have shown that CAM has a period similar to that of periodic breathing (tables 9.1 and 9.2) and when infants exhibit periodic breathing the period of that behaviour and CAM coincide (sections 6.3.3 and 9.5.5). Our data indicate a increased incidence of CAM in infants likely to be at risk of sudden infant death syndrome and a higher incidence of CAM during apneaic episodes of bronchopulmonary dysplastic infants (section 9.5.4). Our evidence demonstrates that CAM is ubiquitous and is a manifestation of periodic breathing during eupnea. Section 11.1 provides a summary of the mathematical techniques of this thesis and the limitations of the results obtained. Section 11.2 describes some consequences and future directions for this research.

11.1 Summary To reach the conclusions outlined above it has been necessary to apply many existing techniques from dynamical systems theory as well as develop several new tools. In chapter 4 we described a new type of surrogate data based on nonlinear modelling techniques. Simulations from nonlinear models of a data set may be used as surrogate data to test the hypothesis that the data came from a system consistent with some general class of dynamical system, which, includes that model. The scope of this hypothesis testing technique is determined by proposition 4.1. We have shown that the correlation dimension is a pivotal test statistic, for traditional linear surrogate techniques as well as nonlinear hypothesis testing, using cylindrical basis model simulations as surrogates. We demonstrated that it is necessary to numerically test the broadness of the class of functions for which the probability density function of the test statistic is the same. Stability analysis of xed points (section 7.2) and periodic orbits (Floquet theory, section 10.1), qualitative features of the asymptotic behaviour (section 7.3) and analysis of rst return maps (section 10.2) have all demonstrated results consistent with CAM. 1

174

Chapter 11. Conclusion

Chapter 5 demonstrated the selection of appropriate values of the embedding parameters  and de for our data. In this section we also discussed an extension of uniform embeddings to include nonuniform and variable embedding strategies, these concepts have previously been discussed by Judd and Mees [64]. Application of modelling procedures suggested by Judd and Mees [62] to respiratory data recordings produced unsatisfactory results. Simulations from these models exhibited symmetric wave forms, unlike the data, and would often exhibit stable xed points, unlike most infants. However modi cations to this algorithm, described in chapter 6, improved the results suciently so that nonlinear surrogate testing was unable to distinguish between data and surrogates (section 6.3.3 and chapter 8). These new modelling techniques and alterations to the algorithm suggested in [62] produced models which more accurately model the dynamics of respiration. Simulations from these models exhibited stable periodic or quasi-periodic orbits and had wave forms similar to the data. Using free run predictions from these models we demonstrated that immediately before the onset of periodic breathing, CAM is evident in normal respiration. Asymptotically, models tted to eupnea immediately preceding periodic breathing exhibit cyclic amplitude modulation with a period identical to the period of periodic breathing. Section 6.4 brie y proposed some alternative methods for dealing with non-Gaussian and non-identically distributed noise | one of these techniques was utilised in chapter 8. A genetic algorithm was discussed in section 6.5 and shown to be a viable alternative to the nonlinear optimisation techniques described in section 6.2.4 and the embedding simpli cations of section 6.2.6. The modelling techniques developed in chapter 6 proved to be much more e ective in modelling the dynamics of infant respiration. Data from other dynamical systems may still prove a challenge for this modelling regime2 . Chapter 7 was concerned primarily with the application of the methods described in chapter 6. We calculated the location and stability of xed points of cylindrical basis models. Almost all data sets exhibited models for which the largest eigenvalue of the central xed point was complex (section 7.2). This indicates that the dynamics of this system contains a stable focus on at least a two dimensional manifold. However, in all cases the xed points were located away from the data (in phase space). Determining the stability of these xed points therefore required extrapolation of attributes of the tted model. Analysis of the ow (section 7.3) and visualisation of these models (section 7.1) demonstrated that these models have many more common qualitative features and that they exhibit an asymptotically stable periodic or quasi-periodic orbit. In cases which exhibit a quasi-periodic orbit the attractor appears as either a torus or twisted ribbon. In section 7.4 the modelling regime of chapter 6 was extended to explicitly include time dependence. Models built from apparently non-stationary data, speci cally quiet respiration immediately preceding the onset of periodic breathing, exhibit time For example, this modelling technique still assumes Gaussian additive noise (possibly with state dependent variance). 2

11.1. Summary

175

varying behaviour. In some cases these models exhibited period doubling bifurcations and chaos in the rst return maps. This phenomenon did not occur in all models of the same data sets. However, all models which exhibited period doubling bifurcations accurately modelled the data. Cleave and colleagues [17] proposed a Hopf bifurcation model of respiration and have demonstrated that it is consistent with data. Our results demonstrate that period doubling bifurcations may be observed directly from nonlinear models tted to data. These models are not constrained to include a bifurcations, but, in many incidence they do. Our results indicate that a period doubling mechanism may occur immediately preceding a sigh and the onset of periodic breathing. The observation of a toroidal or ribbon-like attractor is consistent with the dimension estimate calculated in chapter 8. Surrogate hypothesis testing3 demonstrated that our data are inconsistent with a monotonic nonlinear transformation of linearly ltered noise and has dynamic structure over more than a single period. To generate adequate nonlinear surrogate data it was necessary to extend the form of the model described in chapter 6 to include nonuniform noise (section 6.4.2). With this additional feature we found that the data and surrogates were indistinguishable (with respect to correlation dimension). We concluded that the respiratory system is consistent with a periodic system with two to three degrees of freedom and small scale high dimensional behaviour. The attractor is likely to be either toroidal or ribbon-like. The results of chapter 8 also indicate that these techniques may be employed to provide an estimate of the relative magnitude of dynamic and observational noise. Our calculations indicate that dynamic noise and observational noise have a di erent e ect on correlation dimension estimates. Dynamic noise will increase correlation dimension over a large range of length scales whilst the e ect of observational noise is limited to the smallest length scales. Hence, provided one has correctly identi ed the deterministic dynamical system, it is possible to adjust the dynamic and observational noise levels of nonlinear surrogates (noise driven simulations) so that the correlation dimension estimate of the data and the distribution of estimates for the surrogates coincide. That is, one may maximise the likelihood of the correlation dimension estimate for the data given the distribution of dimension estimates of the surrogates, over the dynamic and observational noise levels. This method has not been fully developed or tested and some future work is still possible. A closer examination of the additional one or two degrees of freedom evident in models tted to respiratory data and from dimension estimates gave some evidence of cyclic amplitude modulation. In chapter 9, stability analysis of simple linear models (AR(2) models) of tidal volume time series4 was not useful (section 9.3). The results of these calculations was indistinguishable from i.i.d. noise (algorithm 0) surrogates. However, the application of a novel reduced autoregressive modelling algorithm produced signi Using linear and cycle shued surrogates. The tidal volume time series were calculated by locating the peaks and trough of respiratory recordings and determining the di erence between a peak and the following trough. 3 4

176

Chapter 11. Conclusion

cant results (sections 9.4 and 9.5). The algorithm is based on the nonlinear modelling methods described by Judd and Mees [62, 64], however this is a new application of this method and utilises this algorithm to infer the period of periodic behaviour [138]. We found that CAM is ubiquitous and likely to be a manifestation of periodic breathing during eupnea. The reduced autoregressive modelling (RARM) technique we introduced in chapter 9, when applied to detect periodicities in times series constitutes a new signal processing technique and an alternative to Fourier spectral based methods. In [138] we compare the application of RARM to detect periodicities to Fourier spectral techniques (fast Fourier transforms and autocorrelation estimates). The results of this paper demonstrate that the RARM technique detects periodicities present in test data, even when spectral techniques are inconclusive. In this thesis the RARM technique has been applied to detect CAM in infant respiratory patterns. These results are somewhat preliminary, however we demonstrated that it is likely that CAM is ubiquitous and is the same mechanism as that responsible for periodic breathing. Fleming [32, 34] has demonstrated age dependent periodic amplitude modulation in infants responding to a spontaneous sigh. Age dependent e ects of CAM detected by RARM has not yet been investigated. Hathorn [49, 50, 51] investigated amplitude modulation in infant respiration. However the methods used by Hathorn searched for real time scaled modulation, whereas RARM detected CAM in a breath number/amplitude time series. The results of Hathorn, and the results of this thesis may not be directly comparable. Finally, Waggener and colleagues [11, 12, 162, 160, 161] applied Fourier spectral comb lters to detect periodic uctuations in infant respiration. Waggener's conclusions were limited to speci c environment dependent e ects. Finally, we presented some preliminary results utilising existing nonlinear techniques to detect periodic amplitude modulation in the dynamics of models of respiration. Floquet theory (section 10.1) and an analysis of Poincare sections (section 10.2) con rmed the existence of CAM in models tted to respiratory recordings. Stability analysis of models that exhibit a periodic orbit demonstrated the existence of complex eigenvalues associated with that orbit. This indicates that this orbit corresponds to a stable focus of the rst return map. Models which exhibit quasi-periodic dynamics have either periodic or chaotic rst return maps. Some of these results were preliminary and relied heavily on several approximations to estimate the eigenvalues of the periodic orbit. A model with a smaller prediction time step may o er a closer approximation but would require much greater numerical precision.

11.2 Extensions Several important questions concerning CAM remain unanswered. The work in this thesis has identi ed a measurable amplitude modulation during eupnea. We have observed an increased incidence of this during apneaic episodes of infants su ering from

11.2. Extensions

177

bronchopulmonary dysplasia, and an increase incidence of CAM in infants at risk of SIDS. Our current RARM algorithm will detect CAM as \signi cant" according to the description length criteria. Physiologically it would be useful to also have a measure of the strength of CAM. That is, we wish to quantify the \signi cance" of CAM in a given data set. By calculating the description length of a (normalised) data set and the compression obtained with a minimum description length best model one may quantify the \compression per datum". Calculations of this quantity for the time series in this thesis have produced no signi cant results. However, more data may prove useful. Similarly, it may be useful to investigate the change in period of CAM within one infant, between groups of infants, and in various physiological states. Our data provide evidence of a link between CAM and periodic breathing. We have observed that the period of CAM coincides with the period of periodic breathing. Furthermore, we have preliminary evidence of period doubling bifurcation and the onset of chaos immediately preceding an episode of periodic breathing. CAM detected preceding a sigh may only be a stationary linear approximation to the nonlinear bifurcation that has been observed in some models. To explore this area further it is necessary to improve the nonlinear modelling techniques. Although we have been able to observe a period doubling bifurcation and demonstrate that it provides a satisfactory description of the dynamics of respiration we have not been able to produce this phenomenon consistently. Our results do not support this as the only satisfactory description of the dynamics of respiration preceding the onset of periodic breathing. In this thesis we have adapted modelling algorithms described by other authors to produce consistent accurate models of the stationary respiratory process during quiet sleep. Further improvements to this, or some other, modelling algorithm may yield consistent models of a bifurcation preceding a sigh and the onset of periodic breathing. Regardless, the nonlinear modelling techniques employed in this thesis have been demonstrated to provide evidence of CAM from short experimental data sets. RARM techniques require relatively large data sets, cylindrical basis modelling methods identify CAM in far short recordings5 . Development of these modelling techniques and further experiments may yield signi cant results in our understanding of CAM. There are several directions for the further development of the cylindrical basis modelling algorithm discussed in this thesis. A di erent implementation of a genetic algorithm may yield more useful results. At present the genetic algorithm is only used to optimise the \sensitivity" of a single basis function. If one has a suitable representation of the entire cylindrical basis model it may be possible to apply a genetic algorithm technique to select the model with optimal description length. Our calculations have also indicated that the noise present in these models is signi cant. Correlation dimension and nonlinear surrogates o er a way of estimating the level of observational and dynamics Typically, RARM requires 10 minutes of continuous (quiet) sleep to identify CAM. Cylindrical basis models may be built from 1 or 2 minutes of data and identify CAM. 5

178

Chapter 11. Conclusion

noise present in a model, but the cylindrical basis modelling procedure largely relies on i.i.d. noise. We have implemented models with noise of variable (state dependent) amplitude and these have provided more accurate models of this data in some incidences. Ideally one would want to be able to provide a state dependent estimate of the expected distribution of the noise. Conversely, if one were to assume that a model is only an accurate representation of data when the modelling error is i.i.d., then one has another form of surrogate hypothesis test. For a given model one may test the hypothesis that the model is an accurate representation of data by comparing the modelling errors to i.i.d. noise (an algorithm 0 surrogate test applied to the residuals). This could provide an alternative modelling criterion to Rissanen's description length and the Schwarz and Akaike information criteria. Our calculations of dynamic quantities (speci cally, the application of Floquet theory to \periodic orbits") of this dynamical system have demonstrated another weakness of this modelling method. Finite sampling of an experimental system gives one a discrete time series, from this we build a model of the map of that system. However, the underlying dynamical system is undoubtedly continuous and one is more interested in properties of the ow of this system. Estimating eigenvalues of a periodic orbit of a ow from an \almost" periodic orbit of a model of a map is numerically dicult. Ideally one would want to be able to extract the continuous dynamics directly from the data [141, 142].

179

Part V

Appendices

APPENDIX A

181

Results of linear surrogate calculations Table A.1 shows the number of standard deviations between the values of dc ("0) for data and surrogate, for the value of log("0 ) which gave the greatest di erence. This is calculated over the range ;2:5  log("0)  ;0:5, and for de = 3; 4; 5. Data are from infants at two months of age. The symbol n/a indicates that none of the surrogates produced convergent dimension estimate at any value of "0 . For each data set and each hypothesis test there are three pairs of numbers. These three pairs of numbers are the results for de = 3; 4; 5 respectively. The rst number is the number of standard deviations by which the mean value of dimension for the surrogates exceeded that for the data. The second number (in parentheses) is the value of log("0 ) for which this occurred.

Appendix A. Results of linear surrogate calculations

182

subject data algorithm 0 1 1-1 4.1 ( -1.9) 6.8 ( -1.8) 7.9 ( -1.7) 1-2 6.0 ( -1.7) 10.6 ( -2.1) 12.2 ( -2.0) 1-3 5.2 ( -1.5) 6.1 ( -1.7) 40.8 ( -2.5) 1-4 -0.7 ( -2.5) 0.7 ( -1.7) 1.7 ( -2.4) 2 2-1 6.7 ( -2.0) 9.3 ( -2.1) 18.7 ( -2.5) 2-2 -2.3 ( -1.9) -1.7 ( -1.9) -1.3 ( -2.1)

linear surrogates cycle shued surrogates algorithm 1 algorithm 2 split at maximum split at midpoint split at minimum 27.8 ( -2.1) 3.0 ( -1.9) 4.6 ( -2.0) 6.6 ( -2.3) -0.3 ( -2.5) 38.5 ( -2.0) 2.9 ( -1.8) 5.7 ( -2.5) 6.6 ( -1.9) 2.8 ( -2.3) 17.5 ( -1.9) 2.4 ( -1.9) 3.6 ( -2.4) 5.0 ( -2.3) -0.4 ( -2.5) 64.1 ( -2.1) 7.9 ( -1.7) 2.4 ( -1.7) 9.4 ( -1.9) 2.2 ( -2.5) 147.1 ( -2.2) 8.1 ( -1.9) -0.4 ( -2.5) 9.4 ( -2.1) 1.7 ( -2.5) 39.5 ( -2.2) 6.9 ( -2.0) -0.2 ( -2.5) 8.1 ( -2.5) 2.1 ( -2.5) 83.9 ( -1.6) 4.4 ( -1.5) 4.6 ( -1.5) 7.1 ( -2.1) 2.2 ( -1.5) 124.7 ( -1.7) 3.4 ( -2.5) 8.3 ( -2.2) 13.4 ( -2.5) 3.2 ( -2.2) 25.5 ( -2.4) 4.3 ( -2.4) 3.5 ( -2.0) 21.1 ( -2.4) 2.6 ( -2.3) 57.8 ( -1.7) -0.5 ( -2.5) 8.8 ( -2.3) 6.0 ( -2.0) 1.0 ( -1.7) 9.8 ( -1.8) 0.5 ( -1.7) 35.9 ( -2.5) 24.2 ( -2.5) 1.2 ( -2.3) 10.2 ( -1.7) 1.7 ( -2.4) 59.8 ( -2.3) 7.1 ( -2.1) 1.3 ( -2.4) 7.1 ( -1.9) 4.4 ( -2.1) -0.3 ( -2.5) 4.9 ( -1.9) 2.7 ( -1.9) 22.7 ( -1.9) 7.7 ( -2.1) 2.4 ( -1.9) 7.4 ( -1.9) 2.7 ( -1.9) 13.1 ( -1.8) 6.4 ( -2.2) -9.9 ( -2.5) 4.9 ( -2.4) -3.7 ( -2.5) -3.0 ( -1.8) -1.1 ( -1.9) -2.0 ( -2.5) -0.4 ( -2.5) -1.0 ( -2.5) -3.8 ( -1.9) -1.5 ( -1.9) -11.8 ( -2.2) 0.5 ( -1.6) -1.6 ( -2.3) -30.2 ( -1.7) -1.2 ( -2.1) -1.3 ( -2.1) -0.6 ( -2.1) -1.2 ( -2.1) Table A.1: continued on next page.

Table A.1: continued on next page.

linear surrogates cycle shued surrogates subject data algorithm 0 algorithm 1 algorithm 2 split at maximum split at midpoint split at minimum 2 2-3 n/a ( -2.5) 47.0 ( -2.2) n/a ( -2.5) -0.7 ( -2.2) 2.7 ( -2.5) -1.3 ( -1.8) -25.1 ( -2.2) 138.6 ( -2.3) 1.1 ( -2.5) 0.5 ( -2.1) 4.0 ( -2.5) -0.7 ( -2.2) 1.3 ( -2.5) 173.5 ( -2.3) 0.8 ( -2.5) -0.6 ( -2.5) 2.2 ( -2.2) -0.6 ( -2.3) 3 3-1 25.0 ( -2.5) 26.1 ( -2.4) 19.5 ( -1.9) 3.4 ( -2.0) 9.3 ( -2.3) 2.8 ( -1.9) 31.4 ( -2.5) 21.0 ( -2.5) 14.4 ( -2.5) 3.2 ( -2.0) 8.0 ( -2.3) 3.6 ( -2.4) 27.2 ( -2.5) 16.4 ( -2.0) 12.0 ( -2.5) 2.7 ( -2.0) 8.1 ( -2.5) 2.2 ( -2.0) 3-2 8.5 ( -2.2) 83.2 ( -1.1) 9.8 ( -2.2) 3.0 ( -0.9) 9.1 ( -0.9) 1.9 ( -1.4) 23.8 ( -1.8) 102.4 ( -1.2) 19.1 ( -1.8) 14.8 ( -1.7) 39.7 ( -1.7) 14.6 ( -1.8) 6.9 ( -1.6) 140.3 ( -1.0) 6.0 ( -1.8) 2.5 ( -1.0) 6.0 ( -1.3) 0.4 ( -1.5) 3-3 15.2 ( -2.0) 17.7 ( -2.1) 13.5 ( -2.0) -0.7 ( -2.5) 11.5 ( -2.0) 2.8 ( -2.0) 82.7 ( -1.9) 11.4 ( -2.1) 13.6 ( -1.8) -0.4 ( -2.5) 8.3 ( -2.0) 2.3 ( -1.8) 24.9 ( -1.9) 50.0 ( -2.0) 20.2 ( -1.6) -0.4 ( -2.4) 13.0 ( -1.6) -1.5 ( -2.2) 3-4 16.6 ( -2.0) 28.2 ( -2.0) 17.2 ( -2.0) -0.5 ( -2.5) 7.4 ( -2.0) 2.6 ( -2.0) 69.5 ( -1.8) 78.4 ( -2.1) 22.4 ( -2.0) -0.6 ( -2.5) 6.0 ( -2.0) 3.9 ( -1.8) 37.0 ( -2.0) 136.6 ( -2.0) 8.2 ( -2.0) -0.9 ( -2.5) 9.5 ( -2.4) 2.9 ( -2.2) 3-5 17.0 ( -1.9) 66.9 ( -2.0) 13.0 ( -1.9) 2.8 ( -1.9) 6.5 ( -1.9) 1.3 ( -1.9) 37.3 ( -2.0) 60.5 ( -2.2) 11.7 ( -2.0) -0.5 ( -2.5) 7.2 ( -2.2) 1.9 ( -2.0) 15.6 ( -2.1) 14.5 ( -2.2) 6.8 ( -2.5) -0.4 ( -2.5) 6.8 ( -2.5) 2.1 ( -2.5)

Appendix A. Results of linear surrogate calculations

183

Appendix A. Results of linear surrogate calculations

184

subject data algorithm 0 3 3-6 1.7 ( -1.9) 2.3 ( -2.1) 2.5 ( -1.3) 4 4-1 55.1 ( -0.9) 40.5 ( -0.9) 23.6 ( -1.1) 4-2 42.7 ( -1.1) 35.5 ( -1.2) 28.5 ( -1.1) 4-3 20.3 ( -1.4) 91.2 ( -2.4) 58.9 ( -1.2) 4-4 27.5 ( -1.4) 52.4 ( -1.4) 136.7 ( -2.3) 5 5-1 23.3 ( -1.1) 72.7 ( -2.2) 164.4 ( -1.1)

linear surrogates cycle shued surrogates algorithm 1 algorithm 2 split at maximum split at midpoint split at minimum 8.0 ( -1.4) 1.8 ( -2.2) 2.1 ( -1.3) 3.1 ( -2.2) 1.3 ( -2.2) 2.3 ( -2.1) 1.4 ( -2.1) 2.7 ( -1.4) 13.0 ( -2.1) 3.8 ( -1.4) -0.6 ( -1.5) 1.3 ( -1.3) 1.3 ( -1.4) 2.8 ( -1.4) 1.6 ( -1.6) 21.2 ( -2.0) 62.9 ( -0.9) 16.5 ( -2.2) 28.6 ( -2.2) 1.5 ( -2.1) 16.3 ( -2.1) 92.9 ( -0.9) 8.0 ( -2.0) 39.7 ( -2.1) 2.2 ( -0.8) 112.7 ( -1.1) 62.6 ( -0.8) 35.0 ( -0.6) 6.7 ( -0.6) 6.8 ( -0.6) 104.4 ( -1.3) 36.5 ( -2.5) 32.0 ( -2.4) 15.3 ( -2.5) 1.5 ( -0.8) 25.5 ( -2.3) 118.1 ( -1.1) 13.1 ( -2.3) 17.6 ( -2.2) 2.8 ( -2.5) 19.1 ( -2.3) 22.3 ( -1.1) 5.1 ( -0.9) 8.4 ( -2.3) 2.3 ( -2.2) 31.1 ( -2.3) 14.0 ( -1.4) -2.5 ( -2.5) 27.0 ( -0.9) 6.1 ( -0.9) 150.3 ( -1.4) 64.9 ( -2.5) -267.7 ( -2.5) 7.8 ( -2.4) 2.2 ( -2.5) 144.6 ( -1.5) 26.2 ( -1.2) -1.4 ( -2.4) 13.0 ( -1.1) 1.6 ( -2.0) 120.5 ( -1.4) 16.5 ( -1.4) -0.8 ( -2.5) 9.5 ( -2.5) 3.4 ( -2.5) 151.7 ( -1.5) 10.8 ( -1.6) 83.1 ( -2.5) 21.1 ( -2.5) 3.1 ( -2.5) 22.4 ( -1.5) 142.8 ( -1.2) 6.8 ( -2.3) 23.4 ( -1.2) 3.0 ( -2.5) 80.0 ( -1.3) 15.8 ( -1.2) 6.7 ( -1.0) 29.2 ( -2.4) 3.2 ( -2.4) 104.8 ( -1.3) 19.2 ( -1.2) 5.6 ( -1.1) 45.4 ( -2.3) 6.3 ( -2.4) 35.7 ( -1.3) 21.3 ( -1.1) 5.7 ( -1.9) 4.8 ( -1.1) 2.4 ( -2.2) Table A.1: continued on next page.

Table A.1: continued on next page.

linear surrogates cycle shued surrogates subject data algorithm 0 algorithm 1 algorithm 2 split at maximum split at midpoint split at minimum 6 6-1 64.9 ( -0.7) 11.3 ( -2.2) 10.4 ( -1.5) 14.7 ( -2.1) 19.7 ( -2.1) -0.8 ( -2.2) 117.2 ( -1.8) 74.7 ( -1.0) 7.8 ( -1.9) 14.3 ( -2.0) 11.1 ( -2.0) 2.2 ( -2.3) 436.9 ( -0.7) 92.3 ( -2.5) 284.6 ( -0.6) 232.0 ( -0.5) 86.0 ( -2.0) 1.0 ( -1.9) 7 7-1 -0.7 ( -2.5) 102.3 ( -2.2) 1.0 ( -2.1) 1.2 ( -2.1) 9.4 ( -2.5) 3.7 ( -2.1) -3.6 ( -2.5) 128.8 ( -2.2) -2.6 ( -2.5) -0.8 ( -2.5) 6.4 ( -2.0) 4.9 ( -2.0) 5.6 ( -2.1) 18.3 ( -2.4) 2.6 ( -2.2) -0.5 ( -2.5) 6.6 ( -2.0) 4.4 ( -2.0) 7-2 3.6 ( -2.0) 26.6 ( -2.1) 2.9 ( -2.0) -0.4 ( -2.5) 9.0 ( -2.3) 4.3 ( -2.3) 8.9 ( -1.9) 23.1 ( -2.1) 8.4 ( -1.9) 0.7 ( -1.9) 5.8 ( -2.5) 3.7 ( -1.9) 10.5 ( -1.9) 160.1 ( -1.9) 53.2 ( -1.8) 0.6 ( -1.8) 5.2 ( -1.9) 7.3 ( -1.8) 8 8-1 84.8 ( -0.9) 18.0 ( -1.4) 83.9 ( -0.9) 2.9 ( -1.5) 18.0 ( -0.9) 37.5 ( -1.0) 151.9 ( -1.0) 106.7 ( -1.3) 129.9 ( -0.9) 3.0 ( -1.2) 14.7 ( -0.9) 3.0 ( -1.2) 61.5 ( -1.9) 14.9 ( -1.3) 13.2 ( -1.6) 3.4 ( -1.5) 82.0 ( -2.0) -1.3 ( -2.2) 9 9-1 12.3 ( -2.2) 30.3 ( -1.4) 7.5 ( -1.9) 23.5 ( -2.1) 6.6 ( -2.4) 3.5 ( -1.9) 63.2 ( -2.4) 21.0 ( -2.2) 8.0 ( -2.3) 37.4 ( -2.2) 8.2 ( -2.4) 15.9 ( -2.5) 13.6 ( -1.4) 14.9 ( -1.5) 6.4 ( -1.4) 22.1 ( -2.1) 6.9 ( -1.2) 3.3 ( -1.3) 9-2 17.5 ( -1.1) 38.2 ( -1.3) 9.4 ( -1.7) 7.4 ( -1.3) 6.7 ( -1.7) 8.0 ( -2.4) 19.0 ( -2.0) 15.7 ( -1.3) 7.6 ( -1.2) 7.5 ( -1.2) 5.2 ( -1.5) 4.1 ( -1.4) 27.2 ( -1.2) 107.9 ( -1.3) 9.1 ( -1.1) 56.4 ( -2.0) 9.3 ( -2.1) 27.1 ( -2.2)

Appendix A. Results of linear surrogate calculations

185

Appendix A. Results of linear surrogate calculations

186

subject data algorithm 0 9 9-3 23.9 ( -1.8) 40.7 ( -2.0) 37.6 ( -2.0) 10 10-1 58.6 ( -0.8) 132.9 ( -1.0) 109.1 ( -0.9) 10-2 48.3 ( -1.6) 115.0 ( -1.7) 97.4 ( -2.5)

linear surrogates cycle shued surrogates algorithm 1 algorithm 2 split at maximum split at midpoint split at minimum 109.1 ( -1.1) 20.3 ( -2.0) -201.6 ( -2.1) 3.6 ( -1.5) 58.2 ( -1.0) 122.1 ( -1.3) 133.9 ( -2.3) -218.3 ( -2.3) 3.8 ( -1.2) 8.7 ( -2.2) 28.1 ( -1.9) 43.6 ( -2.1) -242.6 ( -2.1) 52.6 ( -2.1) 66.3 ( -2.1) 52.8 ( -1.2) 20.8 ( -0.9) 6.7 ( -1.0) 10.4 ( -0.8) 1.9 ( -0.8) 7.7 ( -1.3) 13.9 ( -1.0) 5.2 ( -0.9) 7.9 ( -1.4) 1.4 ( -0.9) 94.7 ( -1.1) 109.6 ( -0.9) 3.7 ( -0.9) 45.9 ( -1.8) 2.0 ( -0.9) 79.5 ( -1.7) 36.3 ( -1.6) 5.7 ( -1.6) 9.8 ( -1.9) 3.1 ( -1.8) 108.6 ( -1.9) 14.4 ( -1.7) 5.6 ( -1.7) 8.6 ( -1.8) 3.1 ( -1.9) 96.8 ( -1.8) 20.3 ( -1.6) 4.9 ( -1.5) 10.3 ( -1.5) 3.2 ( -1.6)

Table A.1: Hypothesis testing with standard surrogate tests: Shown are the of standard deviation between data and surrogate dc ("0 ) for the value of log("0 ) that yields the greatest value (for ;2:5  log("0 )  ;0:5) and de = 3; 4; 5. Data are from infants at two months of age. The symbol n/a indicates that none of the surrogates produced convergent dimension estimate at any value of ". Algorithm 1 surrogate calculations indicate a clear distinction between all data and surrogates (separation of at least 3 standard deviations in one of de = 3; 4; 5). In all but 5 data sets (1 ; 4, 2 ; 2, 2 ; 3, 3 ; 6, and 7 ; 1) the same is true for algorithm 2 surrogates. Similarly, cycle shued surrogates (either shued at peak, trough or midpoint) are clearly distinct from the data in all cases.

APPENDIX B

187

Floquet theory calculations This appendix contains the results of the Floquet theory calculations of chapter 10. Table B.1 shows estimates of the 6 largest eigenvalues of a periodic orbit of models of 38 data sets from 14 infants.

Appendix B. Floquet theory calculations

188

Subject length largest eigenvalues of orbit 1 2 3 4 5 6 28 1.212 0.6445 0.03023+0.01162i 0.03023-0.01162i 0.01839 0.0123 29 2.781 0.03375+0.1716i 0.03375-0.1716i -0.00601+0.007559i -0.00601-0.007559i 0.00418+0.003989i 29 2.092 -0.02934+0.2282i -0.02934-0.2282i 0.2276 -0.002712+0.01853i -0.002712-0.01853i 38 0.1792+0.2705i 0.1792-0.2705i -0.1306 0.001643 -0.001195 -6.16e-05+0.0003425i 41 0.6839 -0.3401 0.08192 -0.01484+0.0138i -0.01484-0.0138i 0.01242 40 -1.528 0.7309 -0.009669 0.003018 0.002366 -0.0002565+0.001873i 41 1.096 0.1508 -0.06137 0.00279 -0.001297+0.001678i -0.001297-0.001678i 25 1.001 -0.2517 0.03988+0.07281i 0.03988-0.07281i -0.01157+0.02975i -0.01157-0.02975i 32 0 0 0.9128 0.5813 0.02193 -0.01497 11 1.016 -0.0573 -0.04153 0.00916 -0.0003602 5.933e-15 35 0.8621 0.566 -0.08567 -0.001556+0.03784i -0.001556-0.03784i 0.02409 63 1.044 -0.1429 0.0001281 -2.23e-05 -5.656e-06+1.234e-05i -5.656e-06-1.234e-05i 39 0.9183 0.2805 -0.01402 0.001159+0.009884i 0.001159-0.009884i -0.00172+0.00046i 65 43.01 0.776 -0.0006324 0.0001645 -3.324e-06+1.731e-05i -3.324e-06-1.731e-05i 21 0.8103 0.3993 -0.318 0.01634+0.004118i 0.01634-0.004118i -0.01085+0.001889i 30 1.005 0.09508 -0.002396+0.03381i -0.002396-0.03381i 0.01728 0.004994+0.003284i 38 0.9208 0.1668 -0.02759+0.09472i -0.02759-0.09472i 0.0265 0.001076+0.01409i 40 1.038 -0.5377 0.1742+0.04704i 0.1742-0.04704i -0.02303+0.02856i -0.02303-0.02856i 46 -1.536 1.366 0.2298 -0.002385+0.009436i -0.002385-0.009436i -7.359e-05+0.002789i 36 1.009 0.6323 0.01248 -0.006573+0.003399i -0.006573-0.003399i 0.00283+0.001864i 37 0.8418 -0.7235 0.4268 0.02596+0.006182i 0.02596-0.006182i -0.02494 As2t1 As2t2 As3t3 Bs3t1 Bs3t12 Bs3t5 Bs3t8 Cs1t1 Cs1t2 Cs1t3 Cs1t8 Cs2t6 Cs4t2 Ds3t2 Fs1t2 Gs1t2 Gs2t3 Gs2t4 Gs2t6 Gs3t3 Gs4t2

Table B.1: continued on next page.

length largest eigenvalues of orbit 1 2 3 4 5 6 41 1.246 -0.1522 0.02263 -0.01949 0.0007596+0.00204i 0.0007596-0.00204i 34 0.805 0.09677 0.000634+0.001577i 0.000634-0.001577i 0.0007041+0.000537i 0.0007041-0.000537i 20 0.9335 -0.2281 -0.02409 0.01379 -0.005672+0.006925i -0.005672-0.006925i 30 0.6413+0.1885i 0.6413-0.1885i 0.001246+0.003135i 0.001246-0.003135i 0.001293 4.288e-05+0.0006778i 31 2.222 -0.2165 0.05076 -0.01509 0.002812+0.005332i 0.002812-0.005332i 36 0.737+0.2567i 0.737-0.2567i -0.002467+0.0006384i -0.002467-0.0006384i 0.0001184+0.0006608i 0.0001184-0.0006608i 39 1.355 0.6507 0.3215 -0.03247 0.03038 0.001613+0.02618i 41 1.27 -0.6618 0.5183 -0.02349+0.02519i -0.02349-0.02519i -0.01304+0.01893i 43 0.9619 -0.6763 -0.04587 -0.01844+0.00498i -0.01844-0.00498i -0.003138+0.00277i 32 1.029 -0.2356 0.0005757 -7.806e-05+6.176e-05i -7.806e-05-6.176e-05i -3.828e-06+6.535e-06i 49 0.9088+0.01318i 0.9088-0.01318i 0.0004399+0.0001869i 0.0004399-0.0001869i -3.047e-05+6.099e-05i -3.047e-05-6.099e-05i 30 1.059 0.5588 0.03369 -0.0298 0.009957 0.003117 41 1.646 0.7 -0.003657 0.001626+0.002005i 0.001626-0.002005i -0.0007428 32 0.5453+0.3211i 0.5453-0.3211i -0.08649+0.1149i -0.08649-0.1149i -0.002606 -0.001001+0.0009805i 23 0.7499 -0.07061 0.05281 -0.006362+0.002284i -0.006362-0.002284i 0.001389+0.006174i 20 0.9076 -0.3391 0.1763 -0.00816+0.02464i -0.00816-0.02464i 0.01351+0.01404i 28 -1.343 0.8858 -0.1509 0.06665 -0.003565+0.0172i -0.003565-0.0172i

Table B.1: Calculation of the stability of the periodic orbits of models: Calculation of the 6 largest eigenvalues of an \almost" periodic orbit of the map F generated as a model of a data set. This map is an approximation to a (presumably) periodic orbit of the ow of the original data. In almost all cases the 6 largest eigenvalues include complex conjugate pairs: evidence of a stable focus in the rst return map. These results are somewhat limited by the numerical accuracy of the procedure (see text).

Hs3t4 Is1t1 Js3t4 Js4t3 Js4t4 Ls3t2 Ls4t3 Ms1t6 Ms2t3 Ms3t1 Ms3t3 Ps1t2 Ps4t3 Qs4t1 Rs1t2 Rs1t7 Rs2t4

Subject

Appendix B. Floquet theory calculations

189

190

Appendix B. Floquet theory calculations

191

Bibliography [1] T. A arimaa and I. A. T. Valimaki, `Spectral analysis of impedance respirogram in newborn infants', Biology of the Neonate 54 (1988), 188{194. [2] H. D. I. Abarbanel, R. Brown, J. J. Sidorowich, and L. S. Tsimring, `The analysis of observed chaotic data in physical systems', Rev M Phys 65 (1993), 1331{1392. [3] P. Achermann, R. Hartmann, A. Gunzinger, W. Guggenbuhl, and A. A. Brobely, `All-night sleep EEG and arti cial stochastic control signals have similar correlation dimensions', Electroencephalogr Clin Neurophysiol 90 (1994), 384{387. [4] H. Akaike, `A new look at the statistical model identi cation', IEEE transactions on Automatic Control 19 (1974), 716{723. [5] A. M. Albano, J. Muench, C. Schwartz, A. I. Mees, and P. E. Rapp, `Singularvalue decomposition and the Grassberger-Procaccia algorithm', Phys Rev A 38 (1988), 3017{3026. [6] A. M. Albano, A. Passamante, and M. E. Farrell, `Using higher-order correlations to de ne an embedding window', Physica D 54 (1991), 85{97. [7] T. Anders, R. Emde, and A. Parmalee (eds.), A manual for standardized terminology, techniques and criteria for scoring of states of sleep and wakefulness in newborn infants (Brain Information Institute/Brain Research Institute, UCLA, Los Angeles, CA, 1971). [8] D. A. Berry and B. W. Lindgren, Statistics: Theory and methods (Brooks/Cole publishing company, 1990). [9] H. Bettermann and P. V. Leeuwen, `Dimensional analysis of RR dynamic in 24 hour electrocardiograms', Acta Biotheor 40 (1992), 297{312. [10] N. Birbaumer, W. Lutzenberger, H. Rau, C. Braun, and G. Mayer-Kress, `Perception of music and dimensional complexity of brain activity', International Journal of Bifurcation and Chaos 6 (1996), 267{278. [11] P. J. Brusil, T. B. Waggener, and R. E. Kronauer, `Using a comb lter to describe time-varying biological rhythmicities', J Appl Physiol 48 (1980), 557{561. [12] P. J. Brusil, T. B. Waggener, R. E. Kronauer, and J. Philip Gulesian, `Methods for identifying respiratory oscillations disclose altitude e ects', J Appl Physiol 48 (1980), 545{556. [13] L. Cao, A. Mees, and K. Judd, `Modeling and predicting nonstationary time series', International Journal of Bifurcation and Chaos 7 (1997), 1823{1831.

192

Bibliography

[14] M. C. Casdagli, L. D. Iasemidis, J. C. Sackellares, S. N. Roper, R. L. Glimore, and R. S. Savit, `Characterizing nonlinearity in invasive EEG recordings from temporal lobe epilepsy', Physica D 99 (1996), 381{399. _ An introduction to optimization, in Wiley-Interscience [15] E. K. Chong and S. H.Zak, Series in Discrete mathematics and optimization (John Wiley & Sons, 1996). [16] J. P. Cleave, M. R. Levine, and P. J. Fleming, `The control of ventilation: a theoretical analysis of the response to transient disturbances', J. Theor. Biol. 108 (1984), 261{283. [17] J. P. Cleave, M. R. Levine, P. J. Fleming, and A. M. Long, `Hopf bifurcations and the stability of the respiratory control system', J. Theor. Biol. 119 (1986), 299{318. [18] D. A. Coast, G. G. Cano, and S. A. Briller, `Use of hidden Markov models for electrocardiographic signal analysis', Journal of Electrocardiology 23 (1990), 184{ 191. Supplement. [19] D. A. Coast, R. M. Stern, G. G. Cano, and S. A. Briller, `An approach to cardiac arrhythmia analysis using hidden Markov models', IEEE Biomed 37 (1990), 826{ 836. [20] K. L. Cooke and J. Turi, `Stability, instability in delay equations modeling human respiration', J Math Biol 32 (1994), 535{543. [21] M. Ding, C. Grebogi, E. Ott, T. Sauer, and J. A. Yorke, `Plateau onset for correlation dimension: when does it occur?', Phys Rev Lett 70 (1993), 3872{3875. [22] W. Ditto, J. Langberg, A. Bolmann, K. McTeague, M. Spano, V. In, B. Meadows, and J. Ne , Controlling chaos in human hearts (1997). Seminar. [23] G. C. Donaldson, `The chaotic behaviour of resting human respiration', Respir Physiol 88 (1992), 313{321. [24] M. Dunne, `Chaos in infants!', Tech. Report (Department of Mathematics, University of Western Australia, 1993). [25] B. Eckhardt and F. Haake, `Periodic orbit quantization of bakers map', J. Phys. A. 27 (1994), 4449{4455. [26] R. J. Elliot, L. Aggoun, and J. B. Moore (eds.), Hidden Markov models: estimation and control, in Applications of Mathematics 29 (Springer-Verlag, New York, 1995). [27] J. D. Farmer, E. Ott, and J. A. Yorke, `The dimension of chaotic attractors', Physica D 7 (1983), 153{180.

Bibliography

193

[28] J. Feldman and J. Smith., `Neural control of respiration in mammals: an overview.', in Regulation of Breathing., Eds. J. Dempsey and A. Pack, pp. 39{ 69 (Marcel Dekker Inc, New York, 1995). [29] J. P. Finley and S. T. Nugent, `Periodicities in respiration and heart rate in newborns', Can J Physiol Pharmacol 61 (1983), 329{335. [30] J. Finley and S. Nugent, `Periodicities in respiration and heart rate in new borns', Can J Physiol Pharmacol 61 (1983), 329{335. [31] R. Fitzhugh, `Impulses and physiological states in theoretical models of nerve membrane', Biophysical Journal 1 (1961), 445{466. [32] P. J. Fleming, A. L. Gonclaves, M. R. Levine, and S. Wollard, `The development of stability of respiration in human infants: changes in ventilatory response to spontaneous sighs', J Physiol 347 (1984), 1{16. [33] P. J. Fleming, M. R. Levine, Y. Azaz, R. Wig eld, and A. J. Stewart, `Interactions between thermoregulation and the control of respiration in infants: possible relationship to sudden infant death', Acta Pdiatr Suppl 389 (1993), 57{59. [34] P. J. Fleming, M. R. Levine, A. M. Long, and J. P. Cleave, `Postneonatal development of respiratory oscillations', Annals of the New York Academy of Sciences 533 (1988), 305{313. [35] A. C. Fowler, G. Kember, P. Johnson, S. J. Walter, P. Fleming, and M. Clements, `A method for ltering respiratory oscillations', J. Theor. Biol. 170 (1994), 273{ 281. [36] A. M. Fraser and H. L. Swinney, `Independent coordinates for strange attractors from mutual information', Phys Rev A 33 (1986), 1134{1140. [37] A. Galka, T. Maa, and G. P ster, `Estimating the dimension of high-dimensional attractors: A comparison between two algorithms', Physica D (1998). Submitted. [38] A. Gar nkel, J. N. Weiss, W. L. Ditto, and M. L. Spano, `Chaos control of cardiac arrhythmias', Science 257 (1992), 1230. [39]

, `Chaos control of cardiac arrhythmias', Trends in Cardiovascular Medicine 5 (1995), 76{80.

[40] C. Gaultier, `Apnea and sleep state in newborn and infants', Biology of the Neonate 65 (1994), 231{234. [41] P. Glendinning and C. Sparrow, `Local and global behaviour near homoclinic orbits', J. Stat. Phys. 35 (1983), 645{697.

194

Bibliography

[42] D. E. Goldberg and K. Deb, `A comparative analysis of selection schemes used in genetic algorithms', in Foundations of Genetic Algorithms, Ed. G. J. Rawlins, pp. 69{93 (Morgan Kaufmann Publishers, Inc., San Mateo, CA, 1991). [43] L. Goodman, `Oscillatory behavior of ventillation in resting man', IEEE Biomed 11 (1964), 82{93. [44] P. Grassberger and I. Procaccia, `Characterization of strange attractors', Phys Rev Lett 50 (1983), 346{349. [45]

, `Measuring the strangeness of strange attractors', Physica D 9 (1983), 189{208.

[46] F. S. Grodins, J. Buell, and A. J. Bart, `Mathematical analysis and digital simulation of the respiratory control system', J Appl Physiol 22 (1967), 260{276. [47] J. Guckenheimer and P. Holmes, Nonlinear oscillations, dynamical systems, and bifurcations of vector elds, in Applied mathematical sciences 42 (Springer-Verlag, New York, 1983). [48] V. Haggan and O. Oyetunji, `On the selection of subset autoregressive time series models', Journal of Time Series Analysis 5 (1984), 103{113. [49] M. Hathorn, `The rate and depth of breathing in new born infants in di erent sleep states', J Physiol 243 (1974), 101{113. [50]

, `Analysis of periodic changes in ventilation in new born infants', J Physiol 285 (1978), 85{89.

[51]

, `Respiratory modulation of heart rate in new born infants', Early Human Development 20 (1989), 81{99.

[52] H. Hayashi and S. Ishizuka, `Chaotic response of the hippocampal CA3 region to a mossy ber stimulation in vitro', Brain Research 686 (1995), 194{206. [53] M. P. Hlastala and A. J. Berger, Physiology of respiration (Oxford University Press, New York, 1996). [54] F. Hoppensteadt and C. Peskin, Mathematics in medicine and the life science, in Texts in Applied Mathematics 10 (Springer-Verlag, New York, 1992). [55] F. Hoppensteadt and P. Waltman, `A ow mediated control model of respiration', in Some mathematical questions in biology, Ed. S. A. Levin, pp. 211{218 (The American Mathematical Society, Providence, Rhode Island, 1979). [56] D. Hoyer, K. Schmidt, U. Zwiener, and R. Bauer, `Characterization of complex heart rate dynamics and their pharmacological disorders by non-linear prediction and special data transformations', Cardiovascular Research 31 (1996), 434{440.

Bibliography

195

[57] C. Hunt, `The cardiorespiratory control hypothesis for sudden infant death syndrome', Clinics in Perinatology 19 (1992), 757{771. [58] T. Ikeguchi and K. Aihara, `Estimating correlation dimensions of biological time series with a reliable method', Journal of Intelligent and Fuzzy Systems 5 (1997), 33{52. [59] P. Johnson and D. Andrews, `Thermometabolism and cardiorespiratory control during the perinatal period.', in Respiratory control disorders in infants and children, Eds. R. Beckerman, R. Brouilette, and C. Hunt, ch. 6, pp. 76{87 (Williams and Wilkin, Baltimore, 1992). [60] K. Judd, `An improved estimator of dimension and some comments on providing con dence intervals', Physica D 56 (1992), 216{228. [61]

429.

, `Estimating dimension from small samples', Physica D 71 (1994), 421{

[62] K. Judd and A. Mees, `On selecting models for nonlinear time series', Physica D 82 (1995), 426{444. [63]

, `Modeling chaotic motions of a string from experimental data', Physica D 92 (1996), 221{236.

[64] K. Judd and A. Mees, `Embedding as a modelling problem', Physica D 120 (1998), 273{286. [65] D. Kaplan and L. Glass, Understanding nonlinear dynamics, in Texts in Applied Mathematics 19 (Springer-Verlag, New York, 1996). [66] D. H. Kelly and D. C. Shannon, `Periodic breathing in infants with near-miss sudden infant death syndrome', Pediatrics 63 (1979), 355{360. [67] M. B. Kennel, R. Brown, and H. D. I. Abarbanel, `Determining embedding dimension for phase-space reconstruction using a geometric construction', Phys Rev A 45 (1992), 3403{3411. [68] M. C. Khoo (ed.), Bioengineering approaches to pulmonary physiology and medicine (Plenum Press, New York, 1996). [69] M. C. Khoo, A. Gottschalk, and A. I. Pack, `Sleep-induced periodic breathing and apnea: a theoretical study', J Appl Physiol 70 (1991), 2014{2024. [70] M. C. Khoo, R. E. Kronauer, K. P. Strohl, and A. S. Slutsky, `Factors inducing periodic breathing in humans: a general model', J Appl Physiol 53 (1982), 644{ 659.

196

Bibliography

[71] D. H. Kil and F. B. Shin, Pattern recognition and prediction with applications to signal characterization, in AIP Series in Modern Acoustics and Signal Processing (American Institute of Physics, Woodbury, New York, 1996). [72] M. H. Kryger (ed.), Respiratory medicine (Churchill Livingstone, 1990). [73] H. Kunsch, `The jackknife and the bootstrap for general stationary observations', Annals of Statistics 17 (1989), 1217{1241. [74] P. Landa and M. Rosenblum, `Modi ed Mackey-Glass model of respiratory control', Phys Rev E 52 (1995), R36{R39. [75] C. Lenfant, `Time dependant variations of pulmonary gas exchange in normal man at rest', J Appl Physiol 22 (1967), 675{684. [76] M. R. Levine, J. P. Cleave, and C. Dodds, `Can periodic breathing have advantages for oxygenation?', J. Theor. Biol. 172 (1995), 355{368. [77] M. R. Levine, J. P. Cleave, and P. J. Fleming, `Stability of the control of breathing: analysis of non linear physiological models', in Fetal and Neonatal Development, Ed. C. T. Jones, pp. 341{345 (Perinatology Press, 1988). [78] N. Lippman, K. M. Stein, and B. B. Lerman, `Nonlinear predictive interpolation', Journal of Electrocardiology 26 (1993), 14{19. Supplement. [79]

, `Nonlinear forecasting and the dynamics of cardiac rhythm', Journal of Electrocardiology 28 (1995), 65{70. Supplement.

[80] G. Longobardo, B. Gothe, M. Goldman, and N. Cherniack, `Sleep apnea considered as a control system instability', Respir Physiol 50 (1982), 311{333. [81] M. C. Mackey and L. Glass, `Oscillations and chaos in physiological control systems', Science 197 (1977), 287{289. [82] J. M. Martinerie, A. M. Albano, A. I. Mees, and P. E. Rapp, `Mutual information, strange attractors and optimal estimation of dimension', Phys Rev A 45 (1992), 7085{7064. [83] G. Mayer-Kress, F. E. Yates, L. Benton, M. Keidel, W. Tirsch, S. J. Poppl, and K. Geist, `Dimensional analysis of nonlinear oscillations in brain, heart and muscle', Math Biosci 90 (1988), 155{182. [84] A. I. Mees, P. E. Rapp, and L. S. Jennings, `Singular{value decomposition and embedding dimension', Phys Rev A 36 (1987), 340{346. [85] W. B. Mendelson, Human sleep: research and clinical care (Plenum Medical Book Company, 1987).

Bibliography

197

[86] M. Mitchell, An introduction to genetic algorithms (MIT Press, 1996). [87] M. Molnar and J. E. Skinner, `Correlation dimension changes of the EEG during the wakefulness{sleep cycle', Acta Biochim Biophys Hung 26 (1991), 121{125. [88] C. F. Murphy, D. J. Dick, S. M. Horner, B. Zhou, F. Harrison, and M. J. Lab, `Load-dependent period-doubling bifurcation in the heart of the anaesthetized pig', Chaos, Fractals and Solitons 5 (1995), 707{712. [89] T. Nguyen and W. Humpage, Basic electromagnetics and electromechnics (The Department of Electrical and Electronic Engineering, The University of Western Australia, Perth, Western Australia, 1991). [90] L. Noakes, `The Takens embedding theorem', International Journal of Bifurcation and Chaos 1 (1991), 867{872. [91] V. Padmanabhan and J. L. Semmlow, `Dynamical analysis of diastolic heart sounds associated with coronary artery disease', Annals of Biomedical Engineering 22 (1994), 264{271. [92] M. Palus and I. Dvorak, `Singular{value decomposition in attractor reconstruction: pitfalls and precautions', Physica D 55 (1992), 221{234. [93] M. Paulus, M. A. Geyer, L. H. Gold, and A. J. Mandell, `Application of entropy measures derived from the ergodic theory of dynamical systems to rat locomotor behaviour', Proc Nat Acad Sc USA 87 (1990), 723{727. [94] J. P. Pijn, J. V. Neerven, A. Noest, and F. H. L. da Silva, `Chaos or noise in EEG signals; dependence on state and brain site', Electroencephalogr Clin Neurophysiol 79 (1991), 371{381. [95] B. Pilgram, W. Schappacher, W. N. Loscher, and G. Pfurtscheller, `Application of the correlation integral to respiratory data of infants during REM sleep', Biol Cybern 72 (1995), 543{551. [96] S. M. Pincus, `Quanti cation of evolution from order to randomness in practical time series analysis', Methods in enzymology 240 (1994), 68{89. [97] M. J. D. Powell (ed.), Nonlinear optimization 1981, in NATO conference series, Series II: systems science (Academic Press, 1982). [98]

, `The theory of radial basis function approximation in 1990', in Advances in Numerical Analysis. Volume II: wavelets, subdivision algorithms and radial basis functions, Ed. W. Light, ch. 3, pp. 105{210 (Oxford Science Publications, 1992).

198

Bibliography

[99] M. Powell, `A fast algorithm for nonlinearly constrained optimization calculations', Lecture Notes in Mathematics 603 (1977), 144{157. [100] K. Prank, H. Harms, M. Dammig, G. Brabant, F. Mitschke, and R.-D. Hesch, `Is there low-dimensional chaos in pulsatile secretion of parathyroid hormone in normal human subjects?', American Journal of Physiology 266E (1994), 653{658. [101] I. Priban, `An analysis of some short term patterns of breathing in man at rest', J Physiol 166 (1963), 425{434. [102] D. Prichard and J. Theiler, `Generalized redundancies for time series analysis', Physica D 84 (1995), 476{493. [103] M. B. Priestly, Spectral analysis and time series (Academic Press, London, 1981). [104]

, Non-linear and non-stationary time series analysis (Academic Press, London, 1989).

[105] W. S. Pritchard, `The EEG data indicate stochastic nonlinearity', Behavioral and Brain Sciences 19 (1996), 308. [106] G. Radons, J. Becker, B. Dulfer, and J. Kruger, `Analysis, classi cations, and coding of multielectrode spike trains with hidden Markov models', Biol Cybern 71 (1994), 359{373. [107] P. E. Rapp, `A guide to dynamical analysis', Integrative Physiological and Behavioural Science 29 (1994), 311{327. [108] P. Rapp, T. Schmah, and A. Mees, Models of knowing and the investigation of dynamical systems. Unpublished. [109] G. J. Rawlins (ed.), Foundations of genetic algorithms (Morgan Kaufmann Publishers, Inc., San Mateo, CA, 1991). [110] J. Rissanen, Stochastic complexity in statistical inquiry (World Scienti c, Singapore, 1989). [111] J. Roschke and J. Aldenho , `The dimensionality of human's electroencephalogram during sleep', Biol Cybern 64 (1991), 307{313. [112] J. Roschke and J. B. Aldenho , `A nonlinear approach to brain function: deterministic chaos and sleep EEG', Sleep 15 (1992), 95{101. [113] O. E. Rossler, `Continuous chaos | four prototype equations', Annals of the New York Academy of Sciences 316 (1979), 376{392. [114] M. Sammon, `Geometry of respiratory phase switching', J Appl Physiol 77 (1994), 2468{2480.

Bibliography

[115]

199

, `Symmetry, bifurcations, and chaos in a distributed respiratory control system', J Appl Physiol 77 (1994), 2481{2495.

[116] M. Sammon, J. R. Romaniuk, and E. N. Bruce, `Bifurcations of the respiratory pattern associated with reduced lung volume in the rat', J Appl Physiol 75 (1993), 887{901. [117]

, `Bifurcations of the respiratory pattern produced with phasic vagal stimulation in the rat', J Appl Physiol 75 (1993), 912{926.

[118] M. P. Sammon and E. N. Bruce, `Vagal a erent activity increases dynamical dimension of respiration in rats', J Appl Physiol 70 (1991), 1748{1762. [119] V. L. Schechtman, M. Y. Lee, A. J. Wilson, and R. M. Harper, `Dynamics of respiratory patterning in normal infants and infants who subsequently died of the sudden infant death syndrome', Pediatr Res 40 (1996), 571{577. [120] G. B. Schmid and R. M. Dunki, `Indications of nonlinearity, intraindividual speci city and stability of human EEG: the unfolding dimension', Physica D 93 (1996), 165{190. [121] T. Schreiber and A. Schmitz, `Improved surrogate data for nonlinearity tests', Phys Rev Lett 77 (1996), 635{638. [122] G. Schwarz, `Estimating the dimension of a model', Annals of Statistics 6 (1978), 461{464. [123] M. Shelhamer, `Correlation dimension of optokinetic nystagmus as evidence of chaos in the oculomotor system', IEEE Biomed 39 (1992), 1319{1321. [124] L. Shil'nikov, `A case of the existence of a countable number of periodic motions', Sov. Math. 6 (1965), 163{166. [125]

, `On the generation of a periodic motion from trajectories doubly asymptotic to an equilibrium state of saddle type', Math. USSR Sbornik. 6 (1968), 427{438.

[126]

, `A contribution to the problem of the structure of an extended neighborhood of a rough equilibrium state of saddle-focus type', Math. USSR Sbornik. 10 (1970), 91{102.

[127] B. W. Silverman, Density estimation for statistics and data analysis, in Monographs on Statistics and Applied Probability (Chapman and Hall, London; New York, 1986).

200

Bibliography

[128] J. E. Skinner, `The role of the central nervous system in sudden cardiac death: heartbeat dynamics in conscious pigs during coronary occlusion, psychologic stress and intracerebral propranolol', Integrative Physiological and Behavioural Science 29 (1994), 355{361. [129] J. E. Skinner, C. Carpeggiani, C. E. Landisman, and K. W. Fulton, `Correlation dimension of heartbeat intervals is reduced in conscious pigs by myocardial ischemia', Circ Res 68 (1991), 966{976. [130] J. E. Skinner and M. Mitra, `Low-dimensional chaos maps learning in a model neuropil (olfactory bulb)', Integrative Physiological and Behavioural Science 27 (1992), 304{321. [131] J. E. Skinner, M. Molnar, T. Vybiral, and M. Mitra, `Application of chaos theory to biology and medicine', Integrative Physiological and Behavioural Science 27 (1992), 39{53. [132] J. E. Skinner, C. M. Pratt, and T. Vybiral, `A reduction in the correlation dimension of heartbeat intervals precedes imminent ventricular brillation in human subjects', Am Heart J 125 (1992), 731{743. [133] M. Small, K. Judd, and S. Stick, `Linear modelling techniques detect periodic respiratory behaviour in infants during regular breathing in quiet sleep', Am J Resp Crit Care Med 153 (1996), A79. (abstract). [134] M. Small and K. Judd, `Using surrogate data to test for nonlinearity in experimental data', in International Symposium on Nonlinear Theory and its Applications, 2, pp. 1133{1136 (Research Society of Nonlinear Theory and its Applications, IEICE, 1997). [135]

, `Comparison of new nonlinear modelling techniques with applications to infant respiration', Physica D 117 (1998), 283{298.

[136]

, `Detecting nonlinearity in experimental data', International Journal of Bifurcation and Chaos 8 (1998), 1231{1244.

[137]

, `Pivotal statistics for non-constrained realizations of composite null hypotheses in surrogate data analysis', Physica D 120 (1998), 386{400.

[138]

, `Detecting periodicity in experimental data using linear modeling techniques', Phys Rev E (1999). In press.

[139] M. Small, K. Judd, M. Lowe, and S. Stick, Detection of periodic breathing during quiet sleep using linear modelling techniques. In preparation.

Bibliography

[140]

201

, `Is breathing in infants chaotic? Dimension estimates for respiratory patterns during quiet sleep', J Appl Physiol 86 (1999), 359{376.

[141] M. Small, K. Judd, and A. Mees, `Modeling continuous processes from data', Physica D (1998). Submitted. [142]

, `Modeling with variable prediction step', Physica D (1998). Submitted.

[143]

, `Testing time series for nonlinearity', Statistics and Computing (1998). Submitted.

[144] R. Smith, `Estimating dimension in noisy chaotic time series', J R Stat Soc Ser B 54 (1992), 329{351. [145] C. Stam, J. Pijn, and W. Pritchard, `Reliable detection of nonlinearity in experimental time series with strong periodic components', Physica D 112 (1998), 361{380. [146] K. J. Stam, D. L. Tavy, B. Jelles, H. A. Achtereekte, J. P. Slaets, and R. W. Keunen, `Non-linear dynamical analysis of multichannel EEG: clinical applications in dementia and Parkinson's disease', Brain Topography 7 (1994), 141{150. [147] R. J. Storella, Y. Shi, H. W. Wood, M. A. Jimenez-Montano, A. M. Albano, and P. E. Rapp, `The variance and the algorithmic complexity of heart rate variability display di erent responses to anaesthesia', International Journal of Bifurcation and Chaos 6 (1996), 2169{2172. [148] F. Takens, `Detecting strange attractors in turbulence', Lecture Notes in Mathematics 898 (1981), 366{381. [149] F. Takens, `Detecting nonlinearities in stationary time series', International Journal of Bifurcation and Chaos 3 (1993), 241{256. [150] J. Theiler, `Estimating fractal dimension', J Opt Soc Am A 7 (1990), 1055{1073. [151] J. Theiler, `On the evidence for low-dimensional chaos in an epileptic electroencephalogram', Phys Lett A 196 (1995), 335{341. [152] J. Theiler, S. Eubank, A. Longtin, B. Galdrikian, and J. D. Farmer, `Testing for nonlinearity in time series: the method of surrogate data', Physica D 58 (1992), 77{94. [153] J. Theiler and D. Prichard, `Constrained-realization Monte-Carlo method for hypothesis testing', Physica D 94 (1996), 221{235. [154] J. Theiler and P. Rapp, `Re-examination of the evidence for low-dimensional, nonlinear structure in the human electroencephalogram', Electroencephalogr Clin Neurophysiol 98 (1996), 213{222.

202

Bibliography

[155] H. Tong, Non-linear time series: a dynamical systems approach (Oxford University Press, New York, 1990). [156] R. G. Turcott and M. C. Teich, `Fractal character of the electrocardiogram: distinguishing heart-failure and normal patients', Annals of Biomedical Engineering 24 (1996), 269{293. [157] B. van der Pol, `On \relaxation-oscillations"', Phil, Mag. 2 (1926), 978{992. [158] K. Vibe and J.-M. Vesin, `On chaos detection methods', International Journal of Bifurcation and Chaos 6 (1996), 529{543. [159] B. Vielle and G. Chauvet, `Cyclic model of respiration applied to asymmetrical ventilation and periodic breathing', J Biomed Eng 15 (1993), 251{256. [160] T. B. Waggener, P. J. Brusil, R. E. Kronauer, R. A. Gabel, and G. F. Inbar, `Strength and cycle time of high-altitude ventilatory patterns in unacclimatized humans', J Appl Physiol 56 (1984), 576{581. [161] T. B. Waggener, I. D. Frantz, B. A. Cohlan, and A. R. Stark, `Mixed and obstructive apneas are related to ventilatory oscillations in premature infants', J Appl Physiol 66 (1989), 2818{2826. [162] T. B. Waggener, I. D. Frantz, A. R. Stark, and R. E. Kronauer, `Oscillatory breathing patterns leading to apneic spells in infants', J Appl Physiol 52 (1982), 1288{1295. [163] T. B. Waggener, D. P. Southall, and L. A. Scott, `Analysis of breathing patterns in a prospective population of term infants does not predict susceptibility to sudden infant death syndrome', Pediatr Res 27 (1990), 113{117. [164] T. B. Waggener, A. R. Stark, B. A. Cohlan, and I. D. F. III, `Apnea duration is related to ventilatory oscillation characteristics in newborn infants', J Appl Physiol 57 (1984), 536{544. [165] C. Wagner, B. Nafz, and P. Persson, `Chaos in blood pressure control', Cardiovascular Research 31 (1996), 380{387. [166] C. L. Webber, Jr. and J. P. Zbilut, `Dynamical assessment of physiological systems and states using recurrence plot strategies', J Appl Physiol 76 (1994), 965{973. [167] B. J. West, Fractal physiology and chaos in medicine, in Studies in Nonlinear Phenomena in Life Sciences 1 (World Scienti c, Singapore, 1990). [168] Y. Yamamoto, R. L. Hughson, J. R. Sutton, C. S. Houston, A. Cymerman, E. L. Fallen, and M. V. Kamath, `Operation Everest II: An indication of deterministic

Bibliography

203

chaos in human heart rate variability at simulated extreme altitude', Biol Cybern 69 (1993), 205{212.