Individuals with autism spectrum disorder (ASD) have previously been shown to have significantly augmented and prolonged event-related potential (ERP) responses to irrelevant, visual stimuli compared to controls at both early (e.g., P100) and later stages (e.g., N200, P300) of visual cue processing and evidence of an overall lack of stimulus discrimination. Abnormally large and indiscriminative cortical responses to sensory stimuli may reflect cortical inhibitory deficits and a disruption in the ratio between cortical excitation and inhibition, resulting in a higher noise and difficulties in filtering out distracter stimuli. Low-frequency (≤1HZ) repetitive transcranial magnetic stimulation (rTMS) has been shown to increase inhibition of stimulated cortex by the activation of inhibitory circuits.
Objectives:
It was our hypothesis that after 12 sessions of low-frequency rTMS applied bilaterally to the dorsolateral prefrontal cortices (DLPFC) in individuals with ASD there would be a significant improvement in ERP indices of selective attention evoked at later (i.e., 300-600 ms) stages of attentional processing as well as an improvement in reaction time and response error rate.
Methods:
We assessed 25 participants with ASD in a visual three-stimuli oddball task using illusory figures before and after 12 sessions of rTMS using a controlled design (25 patients with ASD in active TMS, 20 patients in wait-list group). Participants with ASD (age range 9 to 19 years) were recruited through the Weisskopf Child Evaluation Center (WCEC). Diagnosis was made according to the DSM-IV and further ascertained with the ADI-R. Electroencephalographic (EEG) data were acquired with a 128 channel EGI system. Stimulation in TMS group was done at 1Hz, 90% of motor threshold, weekly with 150 pulses/day.
Results:
Reaction time to targets was not significantly different between groups, however, there was a significant reduction in total error rate as a result of rTMS ( t=2.51, p=0.02). This was mainly due to a reduction in omission errors (t= 2.26, p=0.034). We found a significant improvement in both N200 and P300 ERP indices of selective attention as a result of rTMS. A Stimulus X Treatment interaction reached significance (F=3.42, p=0.037) across both hemispheres indicating a significantly more negative N200 amplitude to target stimuli with significantly less negative amplitudes to non-target stimuli as a result of rTMS. One-way ANOVA analysis revealed a significantly reduced P3b latency to non-target stimuli over the left hemisphere as a result of rTMS (F=4.99, p=0.03). We also found significant reductions in both repetitive behavior and irritability according to clinical and behavioral questionnaires as a result of rTMS.
Conclusions:
This investigation showed that treatment with rTMS significantly improved both N200 and P300 ERP indices of selective attention, reduced response errors to target stimuli, and reduced repetitive behaviors and irritability. We conclude that treatment with low-frequency rTMS significantly improved selective attention and executive functioning in individuals with ASD. Neuromodulation with rTMS should be considered a promising treatment modality targeting some of the core symptoms of ASD.
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