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.

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Saccadic latencies are influenced by what occurred during the previous trial. When the previous trial is an antisaccade, the latencies of both prosaccades and antisaccades are prolonged. The aim of this study was to identify neural correlates of this intertrial effect of antisaccades. Specifically, based on both monkey electrophysiology and human neuroimaging findings, we expected trials preceded by antisaccades to be associated with reduced frontal eye field (FEF) activity relative to those preceded by prosaccades. Twenty-one healthy participants performed pseudorandom sequences of prosaccade and antisaccade trials during functional magnetic resonance imaging (fMRI) with concurrent monitoring of eye position. We compared activity in trials preceded by an antisaccade with activity in trials preceded by a prosaccade. The primary result was that a previous antisaccade prolonged saccadic latency and reduced fMRI activity in the FEF and other regions. No regions showed increased activity. We interpret the reduced FEF activity and slower saccadic responses to reflect inhibitory influences on the response system as a consequence of performing an antisaccade in the previous trial. This demonstrates that neural activity is modulated by trial history, consistent with a rapid, dynamic form of learning. More generally, these results highlight the importance of trial history as a source of variability in both behavioral and neuroimaging studies.

A variety of lesions in different cerebral regions may affect the human ability to orient in the environment, resulting in 'topographical disorientation'. In a recent study, we documented the first case of Developmental Topographical Disorientation (DTD), in a person with a life-long inability to orient despite otherwise well-preserved cognitive functions, and in the absence of a cerebral injury/malformation or other neurological condition. This selective topographical disorientation was due to her inability to form a 'cognitive map', a mental representation of the environment, which in turn impaired her ability to orient in both familiar and unfamiliar surroundings. Here, we describe 120 new cases of DTD recruited via the internet and assessed with an online battery testing their cognitive and orientation skills. We found that people with DTD differ from matched (age, gender and education) healthy controls only in those skills confined to the orientation/navigation domain, among which the ability to form a cognitive map was the most significant factor that distinguished a person affected by DTD from control subjects.