Feb 6, 2011 - over-reliance on subjective interpretation can lead to inter-observer differences in the ... The continuous performance task (CPT) test was orig-.
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Role of computerised continuous performance task tests in ADHD Michael O Ogundele MSc, DTCH, MRCPCH, Hani F Ayyash PhD, MMedSci, PGDipPsych, FRCPCH, Somnath Banerjee MSc (Paed), DCH, FRCPCH
Diagnosis of attention deficit-hyperactivity disorder (ADHD) is traditionally based on subjective assessments of behaviour by clinicians and carers in different settings, but this approach is prone to biases. Recent advances in computerised continuous performance task (CPT) tests have greatly improved their clinical utility in ADHD. In this article, the authors review the history of computerised CPT tests and their potential role in the diagnosis and management of children and adolescents with ADHD.
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ttention deficit-hyperactivity disorder (ADHD) is a heterogeneous neurodevelopmental syndrome characterised clinically by the core signs of inattention, hyperactivity and impulsiveness. The diagnosis of ADHD is hinged on two main sets of clinical diagnostic criteria: the World Health Organization’s ICD10 1 and the American Psychiatr y Association’s DSM-IV.2 Without early diagnosis and treatment, children and adolescents with ADHD may suffer educational and social disadvantage. Estimates of the prevalence of ADHD vary widely within and between countries. The estimated prevalence of ADHD in school-aged children in England and Wales is around 5 per cent (350 000 in England and 21 000 in Wales).3 The need for a more objective ADHD assessment tool It has been argued that ADHD is not a distinct diagnostic entity, but that it is a ‘symptom complex’ characterised by multiple possible aetiologies and a constellation of pathological behaviours.4 There is no single laboratory test or set of physiological features that has been identified as an unequivocal ‘gold standard’ for the diagnosis of ADHD. In the absence of an objective gold standard, the ‘reference standard’ is the clinician’s judgment. The diagnosis of ADHD typically involves obtaining information from multiple sources, including the parents’, teachers’ or (in older adolescents) patient’s own ratings of behaviour, clinical interviews of the parents and child, the clinician’s observations of behaviour and neuropsychological testing. However, this over-reliance on subjective interpretation can lead to inter-observer differences in the diagnosis of ADHD. A multidisciplinary approach to the assessment of ADHD is desirable, especially in severe cases, to determine the presence and severity of symptoms across different settings, tasks and caretakers, and to rule out 8
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other conditions that may account for a child’s attentional problems such as anxiety or learning disability.5 There is a paucity of clinical guidelines in the literature that provide an algorithm for how the wide range of instruments, rating scales, questionnaires and surveys that have been developed should be used to assess ADHD symptoms and in what combination.6 What are continuous performance task tests? The continuous performance task (CPT) test was originally developed to examine the performance of radar operators and was later employed as a neuropsychiatric assessment research tool.7 The CPT test is a computerbased test that involves the rapid presentation of a series of visual or auditory stimuli over a period of time (typically numbers, letters, number/letter sequences or geometric figures) for up to 30 minutes. Subjects taking the CPT tests are instructed to respond to the ‘target’ stimulus by pressing a button and to refrain from responding to ‘non-target’ stimuli. Different versions of CPT have been evaluated in the literature. The most common version presents a single target stimulus to respond to such as the letter ‘X’, in contrast to any other non-target stimulus, and is referred to as the ‘X’ CPT. A more difficult variant of the ‘X’ CPT requires subjects to respond to the main stimulus such as the letter ‘X’ only when it directly follows the letter ‘A’. This format is known as the ‘AX’ CPT. Another common variant is the ‘identical pairs’ CPT in which the subject is required to respond only to consecutive stimuli that are identical, such as ‘AA’ or ‘XX’. Other ways of making the task more difficult include providing additional visual or auditory noises (distractions) to the presented stimuli, such as degrading the stimuli by blurring them on the screen or adding adjacent, ‘distracting’ stimuli – known as ‘noise-generated’ CPT.8 www.progressnp.com
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The child’s age is generally taken into account when selecting the appropriate CPT version. Examples of commercially available CPT tests include TOVA (Test of Variables of Attention), QbTest (Quantified behavioural Test), SCAT (Seidel Continuous Attention Test), GDS (Gordon Diagnostic System), IVA (Integrated Visual and Auditory) CPT, and an auditory version – the Auditory Continuous Performance Test (ACPT). Measuring CPT test performances in ADHD CPT test performances are measured using several direct and derived parameters. Responding to the designated target is referred to as a ‘correct response’, while missing a target is referred to as an ‘omission error’. Response to any stimulus other than the target is referred to as a ‘commission error’, or false alarm. Omission errors have been empirically assumed to measure inattention while commission errors are considered to measure impulsivity. Other measures of CPT responses include the number of correct responses, reaction time and variability in reaction time. A recent development in the CPT test involves the introduction of parameters for independent measurement of levels of motor activity in children with ADHD, as a separate entity from impulsivity and inattention. Normal neurodevelopmental progress may affect the performance of the subject on the CPT test and influence the interpretation of the results. Normative data has been shown to demonstrate progress with age in different parameters of CPT testing, including reaction time (RT), RT standard error, errors of omission, errors of commission and signal detection parameters.9 Significant gender differences were also discovered, which included more impulsive errors, less variability and a faster RT in males. Reliability and validity of CPT measurements The reliability of a diagnostic test refers to the extent to which the test results are consistent over time or across conditions and is generally expressed as a correlation coefficient (or ‘r’). The value of r equals 1.0 if there is a perfect positive correlation, –1.0 for a perfect negative correlation, or 0 if there is no correlation, ie no consistency. A desirable level of reliability for a diagnostic tests is .80 or above.10 For the typical ‘AX’ CPT test, various studies have found test-retest reliability measures ranging from 0.14 to 0.94 for hits, misses (omission errors), commission errors, hit reaction times and the derived inattention and impulsivity scores. Omission errors tend to have the lower reliability measures while commission errors and response times have moderate or high measures respectively. 10
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The validity of a diagnostic test refers to what the test measures and how well it does so. The validity of a test is the most important consideration in test evaluation and must be addressed for three categories: content-related validity, construct-related validity and criterion-related validity. The reported concordance rate between CPT outcome measures and clinical diagnosis of ADHD varies between 44 and 80 per cent.5,11 An analysis of eight studies in which CPT measurements were employed in the diagnosis of ADHD revealed low to moderate measures of sensitivity ranging from 9 to 88 per cent. Measures of specificity ranged from 23 to 100 per cent. However, the studies with higher specificities (100 and 94 per cent) had low sensitivities (13 and 62 per cent, respectively). Thus, it was concluded that the utility of the CPT test as a stand-alone diagnostic tool is not very high.6 More recent studies using DSM-IV and ICD-10 diagnostic criteria have confirmed moderately high levels of sensitivity (72 per cent) and specificity (46-56 per cent).12 The wide ranges observed and apparent conflicts in the measured validity and reliability of CPT tests might be related to the presence of several confounding factors such as developmental changes affecting performances, including sex differences and effect of different comorbidities, all of which require further investigation in larger epidemiological studies. Correlation of ADHD symptoms with CPT performance measures Numerous studies and meta-analyses have shown that children with ADHD perform poorly on CPT tests compared to those without ADHD.13 Prediction of ADHD symptoms from CPT measurements have been based mainly on empirical but poorly researched assumptions. For example, errors of commission (responses that occur when no response is required) are assumed to reflect impulsivity. Errors of omission (the absence of a response to a target) are assumed to reflect symptoms of inattention. In a large epidemiological study that examined the relationships between ADHD symptoms and specific CPT parameters, Epstein et al. found that commission errors and omission errors had a nonspecific relationship to ADHD symptomatology, contrary to predictions.14 Omission errors were related to hyperactivity symptoms, not inattention symptoms, and though commission errors were related to impulsivity symptoms, they were also related to hyperactivity and inattention symptoms. Few studies have compared CPT tests with other more subjective behavioural questionnaires and CPT measurements have been shown to demonstrate higher test-retest reliability.15 www.progressnp.com
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Clinical role of CPT tests in the diagnosis of ADHD In the absence of any unequivocal markers for ADHD, it is suggested that clinicians include instruments that assess parent observations, teacher observations and the child’s test performance (including CPT tests) when making diagnostic and treatment decisions. It is unlikely that any test, rating scale or behavioural assessment will be used as a sole diagnostic tool. The CPT test would be particularly useful in the clinical assessment of a patient with suspected ADHD where the subjective ratings from different settings provide conflicting or equivocal results. It would avoid undue delay in making a firm diagnosis as a result of inconclusive subjective opinions of carers or clinicians. There are conflicting views about the ability of CPT tests to differentiate between different conditions associated with attention deficits. Grouping CPT scores into different sub-functions has been suggested as a way of improving its ability to differentiate ADHD subtypes. Cost implications Most commercially available CPTs are software packages that can be loaded onto a personal computer. The cost of the test packages includes the computer software, a technical manual and unlimited use of the test. The cost of the test packages varies significantly, from approximately £200 up to £1000.6 Titrating and monitoring the treatment of ADHD The most common management strategy for ADHD in the UK is pharmacological intervention, the most widely prescribed treatments being methylphenidate, dexamfetamine and atomoxetine.3 Optimal initial titration and dose adjustment over time for the control of the symptoms are very important objectives for successful treatment. Research evidence suggests that CPT would be a useful objective tool to measure the effect of methylphenidate in children with ADHD compared with the more subjective observations of behaviour. CPT has a potential role in monitoring the need for ongoing therapy in children with ADHD after a prolonged period of stimulant pharmacotherapy. Various studies have demonstrated variable improvements in CPT performance in children with ADHD while on neurostimulant medications compared with placebo.16-19 CPT tests have a potential role in monitoring the need for ongoing therapy in children with ADHD after a prolonged period of stimulant pharmacotherapy.20 Few studies have demonstrated the superiority of CPT tests for assessing the effects of psychostimulants in ADHD patients over other laboratory tools for measuring vigilance such as Progress in Neurology and Psychiatry
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Key points • The continuous performance task (CPT) test is a computer-based test originally developed to examine performance of radar operators, which has been adopted as an objective assessment tool for ADHD • CPT tests require the subject to respond to simple target stimuli and refrain from responding to non-target stimuli • Response to a stimulus other than the target (a commission error) is assumed to measure impulsivity and missing a target (an omission error) is assumed to measure inattention, although the relationship to ADHD symptomatology is still not clearcut • Meta-analyses have shown that children with ADHD perform poorly on CPT tests compared with those without ADHD; however, CPT tests cannot distinguish the diagnosis from other disorders of inattention • CPT tests may have a role in monitoring response to therapy as well as in the diagnosis of ADHD • CPT tests cannot replace subjective behavioural interviews, observations and other clinical assessments, but may be useful as an additional tool in the diagnosis and management of ADHD
the Stroop test.21 A recent review has presented a balanced view of the usefulness and limitations of CPT tests in monitoring the effects of psychostimulants.22 Using OPtax (the research model of the CPT test QbTest), statistically significant results were found for micro-events, spatial scaling, errors of commission, accuracy and variability after methylphenidate treatment in children with ADHD. 23 There are a few instances where stimulant medications may worsen the symptoms of ADHD, and an objective CPT medication trial test (pre- and post-medication) would rapidly predict the outcome, thus preventing long, costly and unsuccessful medical treatment. It is conceivable that use of objective measurements to directly quantify activity, impulsivity and attention would increase the accuracy and quality of medical treatment for children with ADHD. Identifying the aetiology of ADHD Research into genetic polymorphisms Recent advances in identification of candidate genes responsible for the development of ADHD have shown correlations between some neuropsychological phenotypes and some susceptible genes. CPT tests have been widely utilised in ongoing interesting research projects aiming to identify the role of different genetic polymorphisms and environmental factors such as maternal smoking and anxiety in the 12
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aetiology of ADHD. Possible candidate genes being investigated include dopamine D2 and D4 receptor genes (DRD2, DRD4), dopamine transporter gene (DAT1), norepinephrine transporter gene (NET), alpha2A-adrenergic receptor gene (ADRA2A), and solute carrier family 9 (sodium/hydrogen exchanger, member 9) gene (SLC9A9). 24-26 CPT tests have shown high validity and reliability values in relation to the candidate gene studies. High reaction variability time is the most common CPT parameter associated with those carrying certain genetic variants such as DRD4 and DAT1 alleles.27 Neuronal correlates during functional imaging studies CPT tests are commonly used in functional imaging studies such as positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) for elucidating the underlying neurophysiological abnormalities in patients with ADHD. These studies have shown inconsistent abnormalities in frontal lobe activation and frontostriatal dysfunction in children, adolescents and adults with ADHD during inhibitory control tasks.28-30 Other studies have reported more global dysfunction of brain activation in children with ADHD.31 Other areas of attention deficit research CPT tests have also been used widely in different areas of attention deficit research, such as EEG alpha asymmetry, event-related potentials, EEG-vigilance, EEG complexities, the cortisol response to stress, effects of lead poisoning, effects of prenatal smoking, effects of Caesarean section birth, and other environmental aetiological factors. Patient empowerment and improved compliance An objective representation of the symptoms of ADHD, visually presented with the aid of diagrams and graphs, would enable parents, and often patients, to gain a better understanding of the condition and to better appreciate and comply with the medical management proposed by the physician, whether this includes medications or not. Conversely, visual presentation of a normal CPT test may help to convince a parent that their child’s difficulties are not due to ADHD. Many highachieving parents whose children are not doing as well in school as they expect, and are desperately looking for an explanation, are often tempted to ascribe their children’s difficulties to ADHD, unless otherwise convinced. However, CPT tests can only act as an additional diagnostic tool and cannot replace frequent clinic appointments. Further research is needed to assess the impact of incorporation of CPT testing in the routine www.progressnp.com
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diagnostic algorithm of patients with ADHD on patient care and satisfaction. Limitations of CPT measurements There are many limitations to studies attempting to correlate CPT measurements with ADHD symptoms. Many studies in this field are heterogeneous, using different subjective questionnaires or observation assessment tools. Different studies have used different sources of information about ADHD symptomatology, which may include the parents’, teachers’ or clinicians’ obser vations. Furthermore, there is a large number of different CPT tests and designs with varying signal rates and signal probabilities. Most CPT test designs are visual but auditory CPT tests are also available.32 It is unclear if the auditory and the visual CPT tests are measuring the same deficits in children with ADHD. There are few studies comparing the different CPT tests. It is likely that different CPT tests measure different behavioural aspects of ADHD and are therefore not suitable for direct comparison. CPT tests used alone may over-diagnose children with high risk for inattention because they do not differentiate between children with other subclinical conditions. It has been noted that some of the core symptoms of ADHD such as inattention may also be present in other psychiatric conditions, which are indistinguishable by the CPT measurements. CPT identifies disorders of attention in several clinical conditions such as traumatic brain damage and schizophrenia but is unable to distinguish the diagnosis. A patient’s computer skills, level of motivation, mood, intelligence and ability to understand the test instructions may also variably and unpredictably influence the outcome of the CPT test performances independent of the underlying psychopathology. Furthermore, the CPT test is a snapshot assessment of a brief period in time and may not necessarily be representative of the overall clinical performance of the patient. There is also the possible ‘placebo effect’ of being watched while performing the test, which may temporarily influence the level of arousal during the test. Finally, the CPT test may not to able to discriminate between the effects of methylphenidate and other neurostimulants. Conclusion Despite the limitations and drawbacks outlined above, CPT testing appears to have significant adjuvant roles in the diagnosis and management of children and adolescents with ADHD. CPT tests provide clinicians www.progressnp.com
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with an objective method for assessing attention deficits, hyperactivity and impulsivity in children. They have the added advantage of avoiding the subjective biases of clinical interviews and rating scales. They provide patients and carers with easy-to-understand insight into the nature of the condition, and thereby help to improve their active participation and compliance with management. Though the CPT test should not be used as the only tool for the diagnosis of ADHD, it may be useful as a supplement to rating scales and other clinical assessments. Objective measurement of the difficulties experienced by patients using CPT tests in conjunction with the traditional subjective behavioural interviews and observations, could help to ensure the optimal diagnosis and management of children and adolescents with ADHD. An analysis of the use of the CPT testing against standard diagnostic tools to determine the most cost effective test battery is warranted. Declaration of interests None declared. Dr Ogundele is a Specialist Registrar at Alder Hey Children’s Hospital NHS Foundation, Dr Ayyash is an Honorary Senior Clinical Lecturer at Sheffield University Medical School and Consultant Paediatrician at Doncaster Royal Infirmary and Dr Banerjee is a Community Paediatrician at East Kent Hospitals University NHS Foundation Trust References 1. World Health Organization. International Classification of Diseases, 10th edn. Geneva: WHO, 1993. 2. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders 4th edn. Washington DC: APA, 1994. 3. National Institute for Health and Clinical Excellence (NICE). Guideline for attention deficit hyperactivity disorder: diagnosis and management of ADHD in children, young people and adults (final scope). London: NICE, 2006. http://www.nice.org.uk/nicemedia/pdf/ADHDFinalScope.pdf 4. Weinberg WA, Brumback RA. The myth of attention deficit-hyperactivity disorder: symptoms resulting from multiple causes. J Child Neurology 1992;7(4):431-45. 5. DuPaul GJ, Anastopoulos AD, Shelton TL, Guevremont D. Multimethod assessment of attention-deficit hyperactivity disorder: the diagnostic utility of clinic-based tests. J Clin Child Psychol 1992;21(4):394-402. 6. Emergency Care Research Institute (ECRI) Continuous Performance Tests (CPTs) for Diagnosis and Titration of Medication for Attention Deficit Hyperactivity Disorder (ADHD). Plymouth Meeting, PA: ECRI, 2000. http://ablechild.org/right%20to%20refuse/continuous_ performance_tests.htm 7. Grunebaum H, Weiss JL, Gallant D, Cohler BJ. Attention in young children of psychotic mothers. Am J Psychiatry 1974;131(8):887-91. 8. Uno M, Abe J, Sawai C, et al. Effect of additional auditory and visual stimuli on continuous performance test (noise-generated CPT) in AD/HD children - usefulness of noise-generated CPT. Brain and Development 2006;28(3):162-9. 9. Conners CK, Epstein JN, Angold A, Klaric, J. Continuous performance test performance in a normative epidemiological sample. J Abnormal
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predominantly inattentive and combined subtypes of attentiondeficit/hyperactivity disorder. J Child Adolescent Psychopharmacol 2009;19(6):663-71. 22. Riccio CA, Waldrop JJ, Reynolds CR, Lowe P. Effects of stimulants on the continuous performance test (CPT): implications for CPT use and interpretation. J Neuropsychiatry and Clin Neurosci 2001;13(3): 326-35. 23. Heiser P, Frey J, Smidt J, et al. Objective measurement of hyperactivity, impulsivity, and inattention in children with hyperkinetic disorders before and after treatment with methylphenidate. European Child and Adolescent Psychiatry 2004;13(2):100-4. 24. Markunas CA, Quinn KS, Collins AL, et al . Genetic variants in SLC9A9 are associated with measures of attention-deficit/hyperactivity disorder symptoms in families. Psychiatric Genetics 2010;20(2): 73-81. 25. Kollins SH, McClernon FJ, Epstein JN. Effects of smoking abstinence on reaction time variability in smokers with and without ADHD: an exGaussian analysis. Drug and Alcohol Dependence 2009;100(1-2):1 69-72. 26. Kim B, Koo MS, Jun JY, et al. Association between dopamine D4 receptor gene polymorphism and scores on a continuous performance test in Korean children with attention deficit hyperactivity disorder. Psychiatry Investigation 2009;6(3):216-21. 27. Kebir O, Tabbane K, Sengupta S, Joober R. Candidate genes and neuropsychological phenotypes in children with ADHD: review of association studies. J Psychiatry Neurosci 2009;34(2):88-101. 28. Rubia K, Overmeyer S, Taylor E, et al. Hypofrontality in attention deficit hyperactivity disorder during higher-order motor control: a study with functional MRI. Am J Psychiatry 1999;156(6):891-6. 29. Durston S, Tottenham NT, Thomas KM, et al. Differential patterns of striatal activation in young children with and without ADHD. Biol Psychiatry 2003;53(10):871-8. 30. Baumeister AA, Hawkins MF. Incoherence of neuroimaging studies of attention deficit/hyperactivity disorder. Clin Neuropharmacol 2001;24(1):2-10. 31. Li F, Li BJ, Hu DW, et al. [Article in Chinese]. Chinese J Contemporary Paediatrics [Zhongguo dang dai er ke za zhi] 2010;12(1):24-8. 32. Riccio CA, Cohen MJ, Hynd GW, Keith RW. Validity of the auditory continuous performance test in differentiating central processing auditory disorders with and without ADHD. J Learning Disabilities 1996;29(5):561-6.
