Low-Frequency Repetitive Transcranial Magnetic Stimulation (rTMS) Affects Event-Related Potential Measures of Novelty Processing in Autism

In our previous study on individuals with autism spectrum disorder (ASD) (Sokhadze et al., Appl Psychophysiol Biofeedback 34:37-51, 2009a) we reported abnormalities in the attention-orienting frontal event-related potentials (ERP) and the sustained-attention centro-parietal ERPs in a visual oddball experiment. These results suggest that individuals with autism over-process information needed for the successful differentiation of target and novel stimuli. In the present study we examine the effects of low-frequency, repetitive Transcranial Magnetic Stimulation (rTMS) on novelty processing as well as behavior and social functioning in 13 individuals with ASD. Our hypothesis was that low-frequency rTMS application to dorsolateral prefrontal cortex (DLFPC) would result in an alteration of the cortical excitatory/inhibitory balance through the activation of inhibitory GABAergic double bouquet interneurons. We expected to find post-TMS differences in amplitude and latency of early and late ERP components. The results of our current study validate the use of low-frequency rTMS as a modulatory tool that altered the disrupted ratio of cortical excitation to inhibition in autism. After rTMS the parieto-occipital P50 amplitude decreased to novel distracters but not to targets; also the amplitude and latency to targets increased for the frontal P50 while decreasing to non-target stimuli. Low-frequency rTMS minimized early cortical responses to irrelevant stimuli and increased responses to relevant stimuli. Improved selectivity in early cortical responses lead to better stimulus differentiation at later-stage responses as was made evident by our P3b and P3a component findings. These results indicate a significant change in early, middle-latency and late ERP components at the frontal, centro-parietal, and parieto-occipital regions of interest in response to target and distracter stimuli as a result of rTMS treatment. Overall, our preliminary results show that rTMS may prove to be an important research tool or treatment modality in addressing the stimulus hypersensitivity characteristic of autism spectrum disorders.