243 Intracranial Theta-burst Stimulation Modulates Cortical Excitability in a Dose and Location-dependent Fashion

Abstract

INTRODUCTION: Direct electrical stimulation is a powerful therapeutic approach to treating a wide range of brain disorders. In particular, theta-burst stimulation (TBS) which delivers electrical pulses in rhythmic bursts of 3-8 Hz to mimic endogenous brain rhythms, has been increasingly used to improve cognitive processes and relieve symptoms of depression. However, how TBS alters underlying neural activity is poorly understood. METHODS: In nine neurosurgical epilepsy subjects undergoing intracranial monitoring, we applied direct cortical TBS at varying stimulation amplitudes and locations (prefrontal, temporal, parietal). We obtained single-pulse corticocortical evoked potentials (CCEPs) prior to stimulation to map functional connectivity. Intracranial EEG (iEEG) was recorded from non-stimulated electrodes before, during and after TBS. RESULTS: We found that TBS evoked consistent responses after each burst. These responses were observed in regions with high amplitude CCEPs and resting spontaneous delta (1-4 Hz) phase-locking to the stimulation site, consistent with our hypothesis that the underlying functional brain architecture guides information flow after stimulation. Furthermore, we observed changes in cortical excitability over time as measured by changes in amplitude of the TBS evoked responses both within stimulation burst trains and across burst trains. The degree of change in cortical excitability was modulated by anatomical location, proximity of the stimulating electrode to white matter, and current amplitude. CONCLUSIONS: These results indicate that direct cortical TBS produces neural effects that can be measured over time and correlate with baseline biophysical parameters. Thus, personalizing stimulation parameters might be critical to predictably maximize our ability to alter disease-relevant brain networks.