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Abnormal Functional Activation and Maturation of Fronto-Striato-Temporal and Cerebellar Regions During Sustained Attention in Autism Spectrum Disorder
Clodagh M. Murphy, M.R.C.Psych.; Anastasia Christakou, Ph.D.; Eileen M. Daly, Ph.D.; Christine Ecker, Ph.D.; Vincent Giampietro, Ph.D.; Michael Brammer, Ph.D.; Anna B. Smith, Ph.D.; Patrick Johnston, Ph.D.; Dene M. Robertson, M.R.C.Psych.; MRC AIMS Consortium; Declan G. Murphy, M.D., F.R.C.Psych.; Katya Rubia, Ph.D.
Am J Psychiatry 2014;:. doi:10.1176/appi.ajp.2014.12030352
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From the Sackler Institute for Translational Neurodevelopment, the Department of Forensic and Neurodevelopmental Sciences, the Department of Child and Adolescent Psychiatry, and the Centre for Neuroimaging, Institute of Psychiatry, King’s College London; the Behavioural Genetics Clinic, Adult Autism Service, Behavioural and Developmental Psychiatry Clinical Academic Group, South London and Maudsley Foundation NHS Trust; the School of Psychology and Clinical Language Sciences, University of Reading, Reading, U.K.

Address correspondence to Dr. Clodagh M. Murphy (clodagh.m.murphy@kcl.ac.uk).

Copyright © 2014 by the American Psychiatric Association

Received March 15, 2012; Revised October 31, 2013; March 03, 2014; Accepted March 28, 2014.

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Abstract

Objective  Sustained attention problems are common in people with autism spectrum disorder (ASD) and may have significant implications for the diagnosis and management of ASD and associated comorbidities. Furthermore, ASD has been associated with atypical structural brain development. The authors used functional MRI to investigate the functional brain maturation of attention between childhood and adulthood in people with ASD.

Method  Using a parametrically modulated sustained attention/vigilance task, the authors examined brain activation and its linear correlation with age between childhood and adulthood in 46 healthy male adolescents and adults (ages 11–35 years) with ASD and 44 age- and IQ-matched typically developing comparison subjects.

Results  Relative to the comparison group, the ASD group had significantly poorer task performance and significantly lower activation in inferior prefrontal cortical, medial prefrontal cortical, striato-thalamic, and lateral cerebellar regions. A conjunction analysis of this analysis with group differences in brain-age correlations showed that the comparison group, but not the ASD group, had significantly progressively increased activation with age in these regions between childhood and adulthood, suggesting abnormal functional brain maturation in ASD. Several regions that showed both abnormal activation and functional maturation were associated with poorer task performance and clinical measures of ASD and inattention.

Conclusions  The results provide first evidence that abnormalities in sustained attention networks in individuals with ASD are associated with underlying abnormalities in the functional brain maturation of these networks between late childhood and adulthood.

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