Event-Related Potential Study of the Effects of Repetitive Transcranial Magnetic Stimulation on Novelty Processing in Autism

Background: Autism is considered to be a neurodevelopmental disorder characterized by severe disturbances in social relations, impaired development of language and communication skills, and a limited repertoire of behavioral patterns. Neuropathological findings by our group have indicated an increased number of cortical minicolumns with less surrounding neuropil space in the dorsolateral prefrontal cortex (DLPFC) of individuals with autism. Less minicolumnar neuropil space in the DLPC is indicative of a lack of GABAergic inhibitory interneurons leading to an alteration of the excitation-inhibition balance in the DLPFC and lower signal-to-noise ratio. The DLPFC is functionally interconnected with other cortical areas involved in cognitive functions. Repetitive transcranial magnetic stimulation (rTMS) administered at frequencies ≤1 Hz over the DLPFC has proven to increase the amount of inhibitory activity of the stimulated cortical region in studies on depression and anxiety disorders.

Objectives: This study investigated potential positive effects of low frequency rTMS on processing of novel distracters in a visual three-stimulus oddball task in children and young adults with autism.

Methods: To test the effects of rTMS in autism we recruited 11 individuals with a primary diagnosis of an autism spectrum disorder (ASD) and 11 age-matched controls to participate in an event-related potential (ERP) study of novelty processing before and after six sessions of rTMS. Only autistic individuals were enrolled in the rTMS trial, while controls were tested on the same cognitive test twice within a month. RTMS stimulation consisted of 2 sessions per week for three weeks for a total of 150 pulses (0.5 Hz) per day at 90 % of motor threshold.

Results: In a baseline test we found significantly delayed latencies to novel stimuli in the early (P100, N100), and late (P2a, N200, P3a) ERPs over the frontal lobe in autism relative to controls. We found increased amplitudes of the early frontal ERPs to non-target and novel stimuli in autism as well. These results indicate low selectivity and ineffective filtration in early processing stages and reduced activation of integrative regions in the frontal cortices in autism. Over centroparietal channels we found a significant reduction in the amplitude of the N2b and an increase in the latency of the early N100 component to targets in autism. Also, the P3b showed a significantly delayed latency to novel stimuli. These baseline test results suggest that autistic subjects over-process information needed for successful differentiation of target and novel stimuli in the oddball test. After completion of the rTMS treatment individuals with autism group showed a significant reduction in latency of the late frontal components both to target and novel stimuli. Individuals with autism showed a reduction in latency of the late parietal ERPs to novel stimuli while showing an increase in latency to target stimuli. There were no significant changes of ERP components in the repeated test in control group.

Conclusions: These ERP results suggest improved selectivity in early processing stages over the frontal cortices and more efficient differentiation of target and novel stimuli as a result of rTMS treatment in individuals with autism.