Transcranial magnetic stimulation with intracranial recording in humans and primates: a review

Recent studies combining transcranial magnetic stimulation (TMS) with intracranial micro-stereo EEG (µsEEG) or intracranial EEG (iEEG) have significantly advanced our understanding of neural circuits and the effects of exogenous stimulation upon them. These studies leverage the high spatial and temporal resolution of µsEEG and iEEG to illuminate the multifaceted and dynamic aspects of TMS-associated neural modulation. This review focuses on TMS-µsEEG and TMS-iEEG studies in non-human primates and humans. A systematic search of three major databases identified seven non-human primate and six human studies that employed single-pulse (spTMS) and repetitive TMS (rTMS) protocols while measuring intracranial neural activity. TMS effects range from direct influences on neurons near the stimulation site to remote effects in regions not directly stimulated, and finally to broader modulation of brain network interactions. Effects such as single-unit excitation are observed as early as 2 ms after a single TMS pulse, while changes in time-frequency spectra may persist for up to 40 min after a rTMS protocol such as intermittent theta-burst stimulation. Additionally, this review addresses the methodological and safety considerations critical to conducting TMS-µsEEG and TMS-iEEG studies in both non-human primate and human subjects. This review demonstrates the flexibility of TMS-µsEEG and TMS-iEEG models for investigating the spatial distribution of TMS-evoked responses, the electrophysiological correlates of TMS-induced modulation, dynamic TMS-induced changes in network activity, and the neural correlates that accompany TMS-induced behavioural change. Taken collectively, this review underscores the considerable potential of the TMS-µsEEG and TMS-iEEG models for advancing our understanding of brain stimulation as it relates to brain connectivity and function and identifies key areas for future research.