Attention Networks in Autism Spectrum Disorder: A Resting State Functional Connectivity MRI Study Merage aBrain
a Ghane ,
Aarti
a Nair ,
Brandon
a, b,c Keehn ,
Christopher
a Keown ,
Patricia
a,d Shih ,
Jeanne
c Townsend ,
Ralph-Axel
a Müller
Development Imaging Lab, Department of Psychology, SDSU b Children’s Hospital, Boston/Harvard Medical School c Research on Aging and Development Lab, Dept. of Neurosciences, UCSD d Department of Neuroscience, Brown University
Behavioral Correlates
fMRI Results
Introduction
• Within group results showed similar patterns of activation in TD and ASD, with TD results consistent to the networks as presented in Fan et al. (2005). • Group comparisons between TD and ASD showed under-connectivity in ASD for the alerting network at the local level in the right superior temporal gyrus. • For the orienting network seed, areas of both over- and under-connectivity in ASD were found. Under-connected regions consisted of the bilateral superior frontal gyrus, the right SMA, and the right inferior frontal gyrus. Over-connected regions include the right cerebellum, the left anterior cingulate cortex, and the left precuneus. • For the executive control network seed placed in the left pulvinar, over-connectivity in the ASD group was found in left inferior frontal gyrus, left inferior occipital gyrus, and right lateral cerebellum. No major group differences were found using the seed in the left superior frontal gyrus. • Functional connectivity indices (z’) for the alerting network, correlated with the orienting and executive function network indices, showed positive correlation in the ASD group (r = .630, p = .007) and ( r = .736, p = .001), respectively. Similarly, indices for the orienting network were also positively correlated with the executive control network indices solely in the ASD group (r = .602, p = .011). No significant between-network correlations were found in the TD group (all p > .10)
Alerting and ADOS Socio-Communicative Skills
• ANT Alerting
• Attention processes are crucial for various aspects of cognitive and affective functioning. • There is evidence of three functionally separate but interrelated attention networks: alerting, orienting, and executive control (Posner & Fan, 2004). • Individuals with Autism Spectrum Disorder (ASD) show impaired social interaction and communication, as well as repetitive or restrictive behaviors and interests (DSM-IV, 2000). • Research in ASD has indicated pervasive abnormalities of attention (Allen & Courchesne, 2001). • Atypical attention modulation may contribute to the development of sociocommunicative deficits in ASD. • Functional connectivity magnetic resonance imaging (fcMRI) measures the correlation of the blood oxygen level dependent (BOLD) signal between brain regions, which is considered an indicator of network organization. Resting state fcMRI identifies intrinsic (spontaneous) BOLD correlations within functional networks. • The Attention Network Test (Fan et al., 2002) was used to assess attentional efficiency. A previous behavioral ANT study suggested that attention networks may function less independently in ASD compared with TD individuals (Keehn et al., 2010).
Alerting Network
•
Correlations between alerting network efficiency and ADOS scores for sociocommunicative skills indicated a positive relationship (r = .671, p = .034). Results imply that socio-communicative symptom severity is related to greater alerting network inefficiency.
ADOS Socio-Communicative Skills
Alerting and ADOS Social Interaction
The present study utilized resting state functional connectivity and the ANT to assess network organization and efficiency in adolescents with ASD. To investigate relationships between attentional efficiency, network connectivity, and ASD symptomatology, we examined correlations between diagnostic measures and behavioral and neural indices of network efficiency.
•
Fig. 1. Local under-connectivity in ASD in the right superior temporal gyrus for seed in the same area.
Participants
•
Participants with resting state fMRI data included 17 high-functioning adolescents with ASD and 23 age, gender, and IQ matched TD individuals. A subsample with ANT data included 10 ASD and 10 TD individuals (data collection ongoing). TD (n = 23) 4 left-handed; 4 female
L
R
Correlations between measures of alerting network efficiency and diagnostic scores indicate a positive relationship between efficiency in this particular network and ADOS subscale scores for social interaction (r = .757, p = .011). This relationship demonstrates that greater alerting network inefficiency could be related to a higher level of social impairments in ASD.
ANT Alerting
Objective
Orienting Network ADOS Social Interaction
ASD (n = 17) 2 left-handed; 1 female
A
Mean
Range
SD
Mean
Range
SD
p
Age
14.3
12.1-16.8
1.5
14.6
12.1-17.1
1.5
.854
IQ
108.2
88-126
10.4
114.9
81-139
14.5
.355
B
D
C
Orienting and Social Responsiveness Scale Correlation
•
fMRI Data Acquisition • 6-minute resting state functional EPI scan acquired on 3T GE scanner using an 8-channel head coil. • 180 whole-brain volumes, TR: 2000ms, TE: 30ms; flip angle: 90°, 3.4mm slice thickness, 3.4mm2 in-plane resolution fMRI Preprocessing and Analysis • Preprocessed/analyzed using AFNI (Cox et al., 1997) • Band-pass filtering; motion correction; spatial smoothing (6 FWHM); orthogonal white matter and vascular regressors Functional Connectivity Analysis • Attention network ROIs were based on fMRI activation results from Fan et al. (2005) • The peak ROIs for the alerting, orienting, and executive function networks were the right superior temporal gyrus, the left Broadman Area 37, and the thalamus (left-pulvinar) respectively. An additional seed for the executive function network was placed in the right superior frontal gyrus. • Single 6 mm spherical seeds were placed in regions showing peak activation for each network. • A whole brain correlation analysis was performed with peak seed time series. • All connectivity thresholds have been corrected to p = .05. Behavioral and Diagnostic Assessments • ANT data was available for a subsample of participants. • fcMRI and ANT results were correlated with the Autism Diagnostic Observation Schedule (ADOS) (Lord et al., 1999), the Autism Diagnostic Interview-Revised (ADI-R) (Rutter et al., 2003), and the Social Responsiveness Scale (SRS) (Constantino et al., 2003). References Allen, G. & Courchesne, E. (2001). Attention function and dysfunction in autism. Frontiers in Bioscience, Vol. 6, pp. D105-119. Constantino, J.N., et al. (2003). Validation of a brief quantitative measure of autistic traits: comparison of the social responsiveness scale with the autism diagnostic interview-revised. Journal of Autism and Developmental Disorders, Vol. 33, No. 4, pp. 427-433. Fan, J., McCandliss, B.D., Sommer, T., Raz, A. & Posner, M.I. (2002). Testing the efficiency and independence of the attentional networks, Journal of Cognitive Neuroscience, Vol. 14, No. 3, pp. 340-347. Fan, J., McCandliss, B.D., Fossella, J., Flombaum, J.I., & Posner, M.I. (2005). The activation of attentional networks. Neuroimage, Vol. 26, pp. 471-479. Keehn, B., Lincoln, A.J., Müller, R.A. & Townsend, J. (2010). Attentional networks in children and adolescents with autism spectrum disorder. Journal of Child Psychology and Psychaitry, Vol. 51, No. 11, pp. 1251-1259. Lord, C., et al. (1999). Autism Diagnostic Obervation Schedule - WPS (ADOS-WPS). Los Angeles, CA: Western Psychological Services. Posner, M.I. & Rothbart, M.K. (2007). Research on attention networks as a model for the integration of psychological science. Annual Reviews of Psychology, Vol. 58, pp. 1-23. Rutter, M., et al. (2003). Autism Diagnostic Interview - Revised. Los Angeles, CA: Western Psychological Services.
– TD > ASD – ASD > TD Fig.L 2. Under-connectivity for seed in left fusiform gyrus in ASD group in bilateral superior frontal gyri (A), right SMA (A), and right R inferior frontal gyrus (B). Over-connectivity for seed in left fusiform gyrus in ASD group in left precuneus (B), right cerebellum (C), and left anterior cingulate cortex (D).
ANT Orienting
Methods
•
Executive Network
Correlations between ANT measures of orienting network efficiency and total social responsiveness scale scores indicate a positive relationship between orienting network efficiency and social responsiveness in ASD but not in TD (r = .786, p = .012). Greater orienting network inefficiency is possibly related to symptom severity in ASD.
Social Responsiveness Scale - Total
A
B
C
D
Discussion
– TD > ASD – ASD > TD Fig. 3. Over-connectivity for seed in left pulvinar in ASD group in left inferior frontal gyrus (A), left inferior occipital gyrus (B), and lateral right cerebellum (C-D). L
ANT Results
R
Correlations between ANT scores and functional connectivity indices yielded no significant findings.
This study showed mixed over and under-connectivity in ASD for the orienting network, whereas for the executive network only over-connectivity effects were found, possibly suggesting compensatory mechanisms. Remarkable was consistent over-connectivity with the right cerebellar hemisphere for both orienting and executive network seeds. A relationship between network efficiency scores, as measured by the ANT (Fan et al., 2002), and diagnostic assessments of sociocommunicative functioning was also found, suggesting links between attentional abnormalities and sociocommunicative impairment in ASD. FcMRI results showing atypical connectivity for all three attentional networks appear consistent with prior studies of attention in ASD (Allen & Courchesne, 2001) and provide further evidence for atypical attention function in adolescents with this disorder. Furthermore, consistent with behavioral findings (Keehn et al., 2010), correlations found between network connectivity indices suggest the presence of an atypical interdependence between attention networks in ASD.
Limitations Poster presented at the Cognitive Neuroscience Society Meeting, Chicago, IL, March 31- April 3, 2012. Supported by NIH DC006155, MH081023, and NIDCD DC007361. For correspondence or to obtain a copy of this poster, please e-mail
[email protected]. Conflict of interest: None
ANT scores were available only for a limited subsample. ROI seeds were chosen from an activation based fMRI study performed with adults.
