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Response monitoring, repetitive behaviour and anterior cingulate abnormalities in autism spectrum disorders (ASD).

ABSTRACT: 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.

SUBMITTER: Thakkar KN

PROVIDER: S-EPMC2525446 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:In 1998 secretin, a gastrointestinal hormone, was suggested as an effective treatment for autism spectrum disorders (ASD) based on anecdotal evidence. OBJECTIVES:To assess whether intravenous secretin improves the core features of ASD, other aspects of behaviour or function such as self-injurious behaviour, and the quality of life of affected individuals and their carers. We also assessed whether secretin causes harm. This is an updated version of our review of this topic originally published in 2005. SEARCH METHODS:We searched CENTRAL (2010 Issue 1), MEDLINE (1950 to January 2010) , EMBASE (1980 to 2010 Week 2), PsycINFO (1806 to 2010 Week 2), CINAHL (1938 to January 2010), ERIC (1966 to January 2010), Sociological Abstracts (1952 to January 2010). Sociofile and HealthStar were searched in March 2005 when this review was first published, but were not available for this update. Records were limited to studies published since 1998 as this is when secretin was first proposed as a possible treatment for ASD. We searched reference lists of trials and reviews; we also contacted experts and trialists to find unpublished studies. SELECTION CRITERIA:Randomised controlled trials of intravenous secretin compared to a placebo treatment in children or adults diagnosed with ASD, where at least one standardised outcome measure was reported. DATA COLLECTION AND ANALYSIS:Sixteen studies met the inclusion criteria but for two of these, conducted by Repligen, the only available multisite data were reported in press releases. All outcome data from the other 14 trials were continuous. Where trials used cross-over designs, we conducted analysis on results from the first treatment phase. Where mean change from baseline was reported, we used this in preference to post-treatment scores for meta-analyses or forest plots. Meta-analysis was able to be attempted for only one outcome (Childhood Autism Rating Scale). Insufficient data were available to conduct sensitivity or subgroup analyses to assess the impact of study quality, clinical differences in the intervention or clinically relevant differences between groups, such as age or presence of gastrointestinal symptoms. MAIN RESULTS:Over 900 children were recruited for the secretin trials. Twenty-five established standardised outcome measures were reported to assess core features of ASD, communication, behaviour, visuospatial skills, affect and adverse events. One standardised measure of global impression was also used. No more than four studies used any one outcome measure similarly. When duration from the start of the intervention to outcome assessment was known, outcomes were reported at between three and six weeks. Meta-analysis of data was not possible but there is now consistency of findings, with RCTs of the efficacy of secretin in autism not showing improvements for core features of ASD. AUTHORS' CONCLUSIONS:There is no evidence that single or multiple dose intravenous secretin is effective and as such currently it should not be recommended or administered as a treatment for ASD. Further experimental assessment of secretin's effectiveness for ASD can only be justified if there is new high-quality and replicated scientific evidence that either finds that secretin has a role in neurotransmission in a way that could benefit all children with ASD or identifies important subgroups of children with ASD who could benefit from secretin because of a proven link between the action of secretin and the known cause of their ASD, or the type of problems they are experiencing.

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Response monitoring, repetitive behaviour and anterior cingulate abnormalities in autism spectrum disorders (ASD).

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