Neuromodulation Effects on Error Monitoring and Correction Function in Autism Spectrum Disorders

Background: One important executive function known to be compromised in Autism Spectrum Disorders (ASD) is related to response error monitoring and post-error response correction.  Reports indicated that children with ASD show reduced error processing and deficient behavioral correction after an error is committed. Error sensitivity can be readily examined by measuring event-related potentials associated with responses to errors: the fronto-central error-related negativity (ERN) and the error-related positivity (Pe). The ERN is a response-locked negative deflection, emerging between 40-150 ms after the onset of  an error. Usually this ERN is followed by a positive wave referred to as the Pe potential. It is suggested that the ERN reflects an initial automatic brain response as a result of an error, and the Pe indicates the conscious reflection and comprehension of the error.

Objectives: The goal of our study was to investigate whether behavioral response reaction time (RT),  error rate, post-error RT change, ERN, and Pe will show positive changes following 12-week long repetitive TMS (rTMS) in group of high functioning children with  ASD. Considering that in our prior studies we showed reduction in error rate in ASD group following dorsolateral prefrontal cortex (DLPFC) rTMS, we hypothesized that 12 sessions of rTMS bilaterally applied over the DLPFC will result in improvements reflected in RT, ERN and Pe measures.

Methods: Participants with ASD (N=30) were referred by clinical psychologist. Diagnosis was made according to DSM-IV and further ascertained with ADI-R. Then participants were randomly assigned to either active rTMS treatment (N=15) or wait-list (WTL) groups. There were no significant group differences in age, gender, or IQ. EEG was collected using 128 channel system.  The task involved recognition of a specific illusory shape, in this case a square or triangle, created by three or four inducer disks. Treatment group received 12 weekly 1 Hz rTMS sessions (150 pulses, 90% of motor threshold), while the WTL subjects were tested twice within 12 weeks.

Results: There were no between group differences in reaction time (RT) nor in rate of commission errors. ERN in TMS group became more negative (by 4.99± 4.35 mV, F=5.07, p=0.03). The number of omission errors in TMS group decreased (t=2.26, p=0.034), and post-error RT became slower (from -22.3 ms to 10.6 ms post-TMS). There were no changes in RT, error rate, post-error RT, nor in ERN/Pe measures in the WTL group.   

Conclusions: Our results show significant post-TMS differences in the ERN, as well as behavioral response measures (omission errors, post-error slowing) indicative of improved error monitoring and correction. This executive function is important for ability to correctly evaluate committed error and adjust behavior to prevent from rigid and repetitive actions. Elucidating the neurobiological basis and clinical significance of response monitoring and correction deficits in ASD represents a promising direction for further research. The ERN along with behavioral performance measures can be used as functional outcome measures to assess the effectiveness of  rTMS in autism and thus have practical implications.