Theta-burst stimulation entrains frequency-specific oscillatory responses

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. In particular, it is not understood whether TBS evokes persistent theta oscillations, whether these oscillations occur at the stimulated frequency, and whether stimulation events propagate in a manner consistent with underlying functional and structural brain architecture. To answer these questions, we recruited 20 neurosurgical patients with indwelling electrodes and delivered direct cortical TBS at varying locations and frequencies. We find that TBS rapidly evokes theta rhythms in widespread brain regions, preferentially at the stimulation frequency, and that these oscillations persist for hundreds of milliseconds post stimulation offset. Furthermore, the functional connectivity between recording and stimulation sites predicts the strength of theta response, suggesting that underlying brain architecture guides the flow of stimulation through the brain. These results show that TBS can be used to directly and predictably influence the activity of cognitively-relevant brain networks.