Low-Frequency Repetitive Transcranial Magnetic Stimulation (rTMS) Modulates Evoked-Gamma Frequency Oscillations in Autism Spectrum Disorder (ASD)

Abstract

INTRODUCTION: It has been reported that individuals with Autism Spectrum Disorder (ASD) have abnormal reactions to the sensory environment and visuo-perceptual abnormalities. Electrophysiological research has provided evidence that gamma band activity (30-80 Hz) is a physiological indicator of the co-activation of cortical cells engaged in processing visual stimuli and integrating different features of a stimulus. A number of studies have found augmented and indiscriminative gamma band power at early stages of visual processing in ASD; this may be related to decreased inhibitory processing and an increase in the ratio of cortical excitation to inhibition. Low frequency or 'slow' (≤1HZ) repetitive transcranial magnetic stimulation (rTMS) has been shown to increase inhibition of stimulated cortex by the activation of inhibitory circuits. METHODS: We wanted to test the hypothesis of gamma band abnormalities at early stages of visual processing in ASD by investigating relative evoked (i.e. ~ 100 ms) gamma power in 25 subjects with ASD and 20 age-matched controls using Kanizsa illusory figures. Additionally, we wanted to assess the effects of 12 sessions of bilateral 'slow' rTMS to the dorsolateral prefrontal cortex (DLPFC) on evoked gamma activity using a randomized controlled design. RESULTS: In individuals with ASD evoked gamma activity was not discriminative of stimulus type, whereas in controls early gamma power differences between target and non-target stimuli were highly significant. Following rTMS individuals with ASD showed significant improvement in discriminatory gamma activity between relevant and irrelevant visual stimuli. We also found significant improvement in the responses on behavioral questionnaires (i.e., irritability, repetitive behavior) as a result of rTMS. CONCLUSION: We proposed that 'slow' rTMS may have increased cortical inhibitory tone which improved discriminatory gamma activity at early stages of visual processing. rTMS has the potential to become an important therapeutic tool in ASD treatment and has shown significant benefits in treating core symptoms of ASD with few, if any side effects.

Figure 1

Sensor layout of the 128-channel Geodesic net (EGI, Eugene, Oregon) with selected channels labeled.

Figure 2

We used Kanizsa and non-Kanizsa figures as stimulus material in this experiment. In particular, the stimulus types are Kanizsa square (target), Kanizsa triangle, non-Kanizsa square, and non-Kanizsa triangle. The non-target Kanizsa triangle is introduced to differentiate processing of Kanizsa figures and targets. The stimuli consist of either three or four inducer disks which are considered the shape feature, and they either constitute an illusory figure (square, triangle) or not (collinearity feature).

Figure 3

Relative evoked gamma power at frontal sites (F1, F2) in control (N=20) and ASD groups (N=25) to target and non-target stimuli. Controls have significantly higher evoked gamma power to target Kanizsa stimuli compared to the ASD group (p < .001) with more of a pronounced difference between target and non-target stimuli.

Figure 4

Relative evoked gamma power at frontal sites (F1, F2) in Pre-TMS (N=16) and Post-TMS groups (N=16) to target and non-target stimuli. Relative evoked gamma power significantly increases to target stimuli (p < .001) with more of a pronounced difference between target and non-target stimuli as a result of rTMS.

Figure 5

Average amplitude of evoked gamma oscillations in response to non-target and target Kanizsa stimuli in subjects with ASD before (N = 16) and after rTMS (N = 16) at left lateral frontal (F7) and parietal (P7) EEG recording sites. Single trial EEG was averaged across 30 trials in each condition (non-target, target).

Figure 6

Average amplitude of evoked gamma oscillations in response to non-target and target Kanizsa stimuli in subjects with ASD before (N = 16) and after rTMS (N = 16) at left lateral frontal (F7) and parietal (P7) EEG recording sites. Single trial EEG was averaged across 30 trials in each condition (non-target, target).