Objectives: The goal of our study was to test this theoretical construct of autism and institute a potential therapeutic intervention using low frequency repetitive stimulation (rTMS) known to exert inhibitory effects on the cortex. One aim of our study was to test whether temporal binding of perceptual items in a coherent Gestalt as indexed by induced gamma oscillation coherence and event-related potentials (ERP) is abnormal in autism. This aim used an oddball task with Kanizsa illusory figures known to readily induce gamma oscillations. We proposed that patients with autism will show reduced coherence of gamma activity between areas processing local features and reduced coherence between primary sensory and associative cortical areas. Another aim was to examine effects of rTMS on behavioral, EEG, and ERP outcomes in autism.
Methods: We used rTMS over the dorsolateral prefrontal cortex on a weekly basis for 12 weeks in a group of high-functioning individuals with autism. Twenty five autistic patients and 19 age-matched controls participated in the study. Six patients with autism formed a waiting-list group and were tested twice on Kanizsa oddball task within 2-3 months to rule out repeated test effects. We used oddball task with target and non-target Kanizsa figures, and non-Kanizsa standards at pre-, mid-treatment (6 rTMS) and post-12 rTMS treatment stages. Follow-up test was conducted after 3 months following the rTMS course completion.
Results: Outcome measures based on ERP, induced gamma EEG activity and behavioral measures pre- and post-TMS showed significant improvement which was maintained at the follow-up stage. During baseline test autistic subjects as compared to controls had higher magnitude of ERPs to non-target rather than target stimuli. Autistic patients showed also higher gamma local coherence and lower distal (e.g., frontal vs. parietal) coherence to all stimuli. TMS resulted in a decrease of the amplitude in the frontal and parietal ERPs to non-target stimuli. TMS positively affected the coherence of gamma in response on the ipsilateral frontal and parietal sites. Results of the clinical evaluations showed that following rTMS patients with autism were reported to have reduced repetitive-ritualistic behavior as measured by the Repetitive Behavior Scales. Irritability as measured by Aberrant Behavior Checklist also was significantly reduced.
Conclusions: Selected electrocortical outcome measures were shown as sensitive markers of functional connectivity changes and improved excitatory /inhibitory balance after rTMS trial. The outcomes of extended trial and follow-up suggest that that rTMS offers a potential innovative therapeutic intervention.