Low-frequency repetitive transcranial magnetic stimulation (rTMS) affects event-related potential measures of novelty processing in autism

Abstract

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.

Fig. 1

Amplitude of the left parieto-occipital P50 component shows Stimulus × Time interaction, manifested as a post-TMS increase of P50 to targets and a decrease of amplitude to novels

Fig. 2

Effects of rTMS on fronto-central P50 in response to target and novel stimuli. At post-TMS test P50 amplitude to novels decreased, while to targets increased. The effect was better visible at the left hemisphere. The window for frontal P50 (50–90 ms post-stimulus) is highlighted

Fig. 3

Effects of rTMS on amplitude of the frontal P3b component are manifested as an increase of P3a amplitude to novel distracters and concurrent decrease to targets

Fig. 4

Effects of rTMS on the left parieto-occipital (P07) and occipital (O1) P50 (40–80 ms post-stimulus) in a visual novelty oddball task. At the baseline amplitude of P50 to novels was higher than to targets, whereas at post-TMS test amplitude to targets increased and latency shortened

Fig. 5

Effects of rTMS on midline centro-parietal ERPs (CPz-Pz). Magnitude of the centro-parietal P200 to target stimuli increased. The amplitude of P3b component to targets also increased after rTMS

Fig. 6

Centro-parietal P3b amplitude shows Stimulus (target, standard) × Time (pre-, post-TMS) effect expressed as increased amplitude of P3b to targets and decreased amplitude to standards