Effects of rTMS on Evoked and Induced Gamma Oscillations and Event-Related Potentials in Children with Autism

Background:  Neuropathological, neuroimaging and electrophysiological studies indicate that the brains of individuals with autism spectrum disorder (ASD) manifest a dysfunction in neural circuitry that affects many disparate brain regions. The reported findings have led some investigators to conclude that a functional disconnection of brain regions is a core abnormality of ASD. Gamma oscillations and synchrony are important for the integration of information within and across brain regions. Recent studies indicate that gamma oscillations are involved in a variety of perceptual, cognitive and motor process that are affected in ASD.

Objectives:  In this study we used gamma oscillations along with more traditional event-related potentials (ERP) in a visual oddball task with illusory figures as a functional marker of response to low frequency repetitive transcranial magnetic stimulation (rTMS) in children with ASD.

Methods:  The subject population includes age, gender, and socio-economic matched ASD, and typically developing (TD) children aged 8-19 years. Behavioral evaluations as well as evoked and induced gamma measures and ERPs during visual oddball task with illusory figures tests was collected at pre-, post-TMS course in ASD group (N=23), and at baseline stage in TD group (N=21). After baseline behavioral and EEG/ERP testing the ASD subjects were assigned to 18 weekly sessions of 1 Hz rTMS over the left dorsolateral prefrontal cortex (DLPFC).

Results:  Baseline test showed significant differences between ASD and TD groups mostly in terms of responses to non-target illusory figures where children with autism showed excessive evoked and induced gamma oscillation and higher magnitude of ERP as compared to children. Behavioral response differences were manifested mostly in lower accuracy of motor responses and lower error correction function. The rTMS course resulted in improved accuracy of motor response, lower evoked gamma response to non-targets and increased amplitude of induced gamma to target, along with similar improvements in ERP responses. Behavioral evaluation outcomes showed decreased irritability and hyperactivity scores and decreased rating of repetitive and stereotype behaviors.

Conclusions:  The study support potential utility of gamma oscillations and ERP as ASD biomarkers for functional diagnostics and predictions of clinical and behavioral responses to rTMS in individuals with autism.