Effects of Transcranial Magnetic Stimulation informed by electrophysiological biomarkers in Non-human primates and humans

Abstract

Transcranial Magnetic Stimulation (TMS) is a non-invasive brain stimulation technique that leverages time-varying magnetic fields to induce electric fields that modulate brain activity. It is used in research to study causal brain effects and in clinical settings as a therapeutic tool for neuropsychiatric disorders. Despite the clinical utility, its mechanisms of action are not fully understood. Specifically, the effects of TMS dose, stimulation location and the ambiguity of centrally and peripherally induced effects have not been extensively studied. The standard approach for studying these mechanisms is TMS-EEG in humans which has constraints due to limited spatial specificity. Non-human primate (NHP) models, when combined with invasive electrophysiology, present the unique opportunity of studying these mechanisms with a high spatial specificity. In my first study, I investigated electrophysiological biomarkers of TMS induced brain responses in NHPs with implanted stereotactic EEG electrodes (sEEG). Using these biomarkers, I quantified the dose and location dependent effects of TMS on NHP brain. Furthermore, with carefully designed control experiments, I dissociated centrally induced neural responses from peripherally induced auditory and somatosensory responses. Next, I extended this work to study the biomarkers relevant to TMS effects on human brain. I studied the brain mechanisms pertaining to state-dependent stimulation of human primary motor cortex (M1) using TMS-EEG. Specifically, I investigated the cortical brain responses evoked by stimulating M1 at four phases of primary motor cortical oscillations, mu (8-13 Hz) and beta (14-30 Hz). I compared these responses with behavioral responses measured as motor evoked potentials (MEPs) to elucidate the phase dependent mechanisms of M1. I further studied the importance of oscillatory power on cortical response generation. Collectively, the results of these studies facilitate our understanding about TMS mechanisms. The NHP experiments are highly relevant for interpreting human TMS studies while human experiments are important for interpretation and development of biomarkers for TMS target engagement in clinical applications.