**E**ff**ects of Transcranial Magnetic Stimulation Therapy on Evoked and Induced Gamma Oscillations in Children with Autism Spectrum Disorder**

**Manuel F. Casanova 1,2 , Mohamed Shaban 3 , Mohammed Ghazal 4 , Ayman S. El-Baz 5 , Emily L. Casanova 1 , Ioan Opris <sup>6</sup> and Estate M. Sokhadze 1,2, \***


Received: 30 May 2020; Accepted: 30 June 2020; Published: 3 July 2020

**Abstract:** Autism spectrum disorder (ASD) is a behaviorally diagnosed neurodevelopmental condition of unknown pathology. Research suggests that abnormalities of elecltroencephalogram (EEG) gamma oscillations may provide a biomarker of the condition. In this study, envelope analysis of demodulated waveforms for evoked and induced gamma oscillations in response to Kanizsa figures in an oddball task were analyzed and compared in 19 ASD and 19 age/gender-matched neurotypical children. The ASD group was treated with low frequency transcranial magnetic stimulation (TMS), (1.0 Hz, 90% motor threshold, 18 weekly sessions) targeting the dorsolateral prefrontal cortex. In ASD subjects, as compared to neurotypicals, significant differences in evoked and induced gamma oscillations were evident in higher magnitude of gamma oscillations pre-TMS, especially in response to non-target cues. Recordings post-TMS treatment in ASD revealed a significant reduction of gamma responses to task-irrelevant stimuli. Participants committed fewer errors post-TMS. Behavioral questionnaires showed a decrease in irritability, hyperactivity, and repetitive behavior scores. The use of a novel metric for gamma oscillations. i.e., envelope analysis using wavelet transformation allowed for characterization of the impedance of the originating neuronal circuit. The results suggest that gamma oscillations may provide a biomarker reflective of the excitatory/inhibitory balance of the cortex and a putative outcome measure for interventions in autism.

**Keywords:** Autism spectrum disorder; evoked and induced gamma oscillations; EEG; TMS; oddball task; reaction time; aberrant and repetitive behaviors
