Background Brain stimulation has emerged as a powerful tool in human neuroscience, becoming integral to next-generation psychiatric and neurologic therapeutics. Theta-burst stimulation (TBS), in which electrical pulses are delivered in rhythmic bouts of 3–8 Hz, seeks to recapitulate neural activity seen endogenously during cognitive tasks. A growing literature suggests that TBS can be used to alter or enhance cognitive processes, but little is known about how these stimulation events influence underlying neural activity. Objective Our study sought to investigate the effect of direct electrical TBS on mesoscale neural activity in humans by asking (1) whether TBS evokes persistent theta oscillations in cortical areas, (2) whether these oscillations occur at the stimulated frequency, and (3) whether stimulation events propagate in a manner consistent with underlying functional and structural brain architecture. Methods We recruited 20 neurosurgical epilepsy patients with indwelling electrodes and delivered direct cortical TBS at varying locations and frequencies. Simultaneous iEEG was recorded from non-stimulated electrodes and analyzed to understand how TBS influences mesoscale neural activity. Results We found that TBS rapidly evoked theta rhythms in widespread brain regions, preferentially at the stimulation frequency, and that these oscillations persisted for hundreds of milliseconds post stimulation offset. Furthermore, the functional connectivity between recording and stimulation sites predicted the strength of theta response, suggesting that underlying brain architecture guides the flow of stimulation through the brain. Conclusions By demonstrating that cortical TBS induces frequency-specific oscillatory responses, our results suggest this technology can be used to directly and predictably influence the activity of cognitively-relevant brain networks.
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