Local brain-state dependency of effective connectivity: evidence from TMS–EEG

Background: Spontaneous cortical oscillations have been shown to modulate cortical responses to transcranial magnetic stimulation (TMS). If not controlled for, they might increase variability in responses and mask meaningful changes in the signals of interest when studying the brain with TMS combined with electroencephalography (TMS–EEG). To address this challenge in future closed-loop stimulation paradigms, we need to understand how spontaneous oscillations affect TMS-evoked responses. Objective: To describe the effect of the pre-stimulus phase of cortical mu (8–13 Hz) and beta (13–30 Hz) oscillations on TMS-induced effective connectivity patterns. Methods: We applied TMS to the left primary motor cortex and right pre-supplementary motor area of three subjects while recording EEG. We classified trials off-line into positive- and negative-phase classes according to the mu and beta rhythms. We calculated differences in the global mean-field amplitude (GMFA) and compared the cortical spreading of the TMS-evoked activity between the two classes. Results: Phase had significant effects on the GMFA in 11 out of 12 datasets (3 subjects × 2 stimulation sites × 2 frequency bands). Seven of the datasets showed significant differences in the time range 15–50 ms, nine in 50–150 ms, and eight after 150 ms post-stimulus. Source estimates showed complex spatial differences between the classes in the cortical spreading of the TMS-evoked activity. Conclusions: TMS-evoked effective connectivity appears to depend on the phase of local cortical oscillations at the stimulated site. This may be crucial for efficient design of future brain-state-dependent and closed-loop stimulation paradigms.