TMS provokes target-dependent intracranial rhythms across human cortical and subcortical sites

Abstract

Transcranial magnetic stimulation (TMS) is increasingly deployed in the treatment of neuropsychiatric illness, under the presumption that stimulation of specific cortical targets can alter ongoing neural activity and cause circuit-level changes in brain function. While the electrophysiological effects of TMS have been extensively studied with scalp electroencephalography (EEG), this approach is most useful for evaluating low-frequency neural activity at the cortical surface. As such, little is known about how TMS perturbs rhythmic activity among deeper structures -- such as the hippocampus and amygdala -- and whether stimulation can alter higher-frequency oscillations. Understanding these effects is necessary to refine clinical stimulation protocols and better use TMS as a neuroscientific tool to investigate causal relationships in the brain. Recent work has established that TMS can be safely used in patients with intracranial electrodes (iEEG), making it possible to collect direct neural recordings at sufficient spatiotemporal resolution to examine oscillatory responses to stimulation. To that end, we recruited 17 neurosurgical patients with indwelling electrodes and recorded neural activity while patients underwent repeated trials of single-pulse TMS at various cortical sites. We found that TMS elicited widespread -- but brief -- changes in spectral power that markedly differed according to the stimulation target. Stimulation to the dorsolateral prefrontal cortex (DLPFC) drove widespread low-frequency increases (3-8Hz) in frontolimbic cortices, as well as high-frequency decreases (30-110Hz) in frontotemporal areas. Stimulation in parietal cortex specifically provoked low-frequency responses in the medial temporal lobe and hippocampus but not other regions. We also found high inter-trial phase consistency at low frequencies in the early post-stimulation period, suggestive of evoked responses. Taken together, we established that exogenous, non-invasive stimulation can be used to (1) provoke phase-locked theta increases and (2) briefly suppress high-frequency activity in a cortico-subcortical pattern that varies by stimulation target.