Brain Advance Access originally published online on June 11, 2008
Brain 2008 131(9):2464-2478; doi:10.1093/brain/awn099
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Response monitoring, repetitive behaviour and anterior cingulate abnormalities in autism spectrum disorders (ASD)
1Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02215, 2Department of Psychology, Suffolk University, Boston, MA 02114, 3Department of Anatomy and Neurobiology, Boston University Medical School, Boston, MA, 4Department of Radiology, Massachusetts General Hospital, 5Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA 02129, 6Harvard Medical School, Boston, MA 02215, 7Department of Neurology and 8Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, BC, Canada
Correspondence to: Dara S. Manoach, 149 13th St, Room 2608, Charlestown, MA 02129, USA E-mail: dara{at}nmr.mgh.harvard.edu
Autism 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.
Key Words: autism; anterior cingulate cortex; response monitoring; functional MRI; diffusion tensor imaging
Abbreviations: ACC, anterior cingulate cortex; ADI-R, autism diagnostic interview-revised; ASD, autism spectrum disorders; BOLD, blood oxygen level dependent; CWP, cluster-wise probability; dACC, dorsal ACC; DTI, diffusion tensor imaging; ERN, error-related negativity; HC, healthy control; IQ, intelligence quotient; MPRAGE, magnetization prepared rapid gradient echo; OCD, obsessive–compulsive disorder; rACC, rostral ACC; TE, echo time; TR, repetition time; WM, white matter
Received December 19, 2007. Revised March 14, 2008. Accepted April 30, 2008.