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dc.contributor.authorThakkar, Katharine N.en_US
dc.contributor.authorPolli, Frida E.en_US
dc.contributor.authorJoseph, Robert M.en_US
dc.contributor.authorTuch, David S.en_US
dc.contributor.authorHadjikhani, Nouchineen_US
dc.contributor.authorBarton, Jason J. S.en_US
dc.contributor.authorManoach, Dara S.en_US
dc.date.accessioned2012-01-11T23:13:27Z
dc.date.available2012-01-11T23:13:27Z
dc.date.copyright2008
dc.date.issued2008-6-11
dc.identifier.citationThakkar, Katharine N., Frida E. Polli, Robert M. Joseph, David S. Tuch, Nouchine Hadjikhani, Jason J. S. Barton, Dara S. Manoach. "Response monitoring, repetitive behaviour and anterior cingulate abnormalities in autism spectrum disorders (ASD)" Brain 131(9): 2464-2478. (2008)
dc.identifier.issn1460-2156
dc.identifier.urihttp://hdl.handle.net/2144/3321
dc.description.abstractAutism spectrum disorders (ASD) are characterized by inflexible and repetitive behaviour. Response monitoring involves evaluating the consequences of behaviour and making adjustments to optimize outcomes. Deficiencies in this function, and abnormalities in the anterior cingulate cortex (ACC) on which it relies, have been reported as contributing factors to autistic disorders. We investigated whether ACC structure and function during response monitoring were associated with repetitive behaviour in ASD. We compared ACC activation to correct and erroneous antisaccades using rapid presentation event-related functional MRI in 14 control and ten ASD participants. Because response monitoring is the product of coordinated activity in ACC networks, we also examined the microstructural integrity of the white matter (WM) underlying this brain region using diffusion tensor imaging (DTI) measures of fractional anisotropy (FA) in 12 control and 12 adult ASD participants. ACC activation and FA were examined in relation to Autism Diagnostic Interview-Revised ratings of restricted and repetitive behaviour. Relative to controls, ASD participants: (i) made more antisaccade errors and responded more quickly on correct trials; (ii) showed reduced discrimination between error and correct responses in rostral ACC (rACC), which was primarily due to (iii) abnormally increased activation on correct trials and (iv) showed reduced FA in WM underlying ACC. Finally, in ASD (v) increased activation on correct trials and reduced FA in rACC WM were related to higher ratings of repetitive behaviour. These findings demonstrate functional and structural abnormalities of the ACC in ASD that may contribute to repetitive behaviour. rACC activity following errors is thought to reflect affective appraisal of the error. Thus, the hyperactive rACC response to correct trials can be interpreted as a misleading affective signal that something is awry, which may trigger repetitive attempts at correction. Another possible consequence of reduced affective discrimination between error and correct responses is that it might interfere with the reinforcement of responses that optimize outcomes. Furthermore, dysconnection of the ACC, as suggested by reduced FA, to regions involved in behavioural control might impair on-line modulations of response speed to optimize performance (i.e. speed-accuracy trade-off) and increase error likelihood. These findings suggest that in ASD, structural and functional abnormalities of the ACC compromise response monitoring and thereby contribute to behaviour that is rigid and repetitive rather than flexible and responsive to contingencies. Illuminating the mechanisms and clinical significance of abnormal response monitoring in ASD represents a fruitful avenue for further research.en_US
dc.description.sponsorshipNational Institute for Mental Health (R01 MH67720, MH72120); Mental Illness Neuroscience Discovery Institute (DOE DE-FG02-99ER62764); National Center for Research Resources (P41RR14075)en_US
dc.language.isoenen_US
dc.publisherOxford University Pressen_US
dc.rightsCopyright 2008 The Author(s) This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.en_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc/2.0/uk/
dc.subjectAutismen_US
dc.subjectAnterior cingulate cortexen_US
dc.subjectResponse monitoringen_US
dc.subjectfMRIen_US
dc.subjectDiffusion tensor imagingen_US
dc.titleResponse Monitoring, Repetitive Behaviour and Anterior Cingulate Abnormalities in Autism Spectrum Disorders (ASD)en_US
dc.typearticleen_US
dc.identifier.doi10.1093/brain/awn099
dc.identifier.pubmedid18550622
dc.identifier.pmcid2525446


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Copyright 2008 The Author(s) This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Except where otherwise noted, this item's license is described as Copyright 2008 The Author(s) This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.