Phase of sensorimotor μ-oscillation modulates cortical responses to transcranial magnetic stimulation of the human motor cortex

Key points Oscillatory brain activity coordinates the response of cortical neurons to synaptic inputs in a phase-dependent manner. Larger motor-evoked responses are obtained in a hand muscle when transcranial magnetic stimulation (TMS) is synchronized to the phase of the sensorimotor mu-rhythm. In this study we further showed that TMS applied at the negative vs. positive peak of the mu-rhythm is associated with higher absolute amplitude of the evoked EEG potential at 100 ms after stimulation. This demonstrates that cortical responses are sensitive to excitability fluctuation with brain oscillations Our results indicate that brain state-dependent stimulation is a new useful technique for the investigation of stimulus-related cortical dynamics. Oscillatory brain activity coordinates the response of cortical neurons to synaptic inputs in a phase-dependent manner. Transcranial magnetic stimulation (TMS) of the human primary motor cortex elicits larger motor-evoked potentials (MEPs) when applied at the negative vs. positive peak of the sensorimotor mu-rhythm recorded with EEG, demonstrating that this phase represents a state of higher excitability of the cortico-spinal system. Here, we investigated the influence of the phase of the mu-rhythm on cortical responses to TMS as measured by EEG. We tested different stimulation intensities above and below resting motor threshold (RMT), and a realistic sham TMS condition. TMS at 110% RMT applied at the negative vs. positive peak of the mu-rhythm was associated with higher absolute amplitudes of TMS-evoked potentials at 70 ms (P70) and 100 ms (N100). Enhancement of the N100 was confirmed with negative peak-triggered 90% RMT TMS, while phase of the mu-rhythm did not influence evoked responses elicited by sham TMS. These findings extend the idea that TMS applied at the negative vs. positive peak of the endogenous mu-oscillation recruits a larger portion of neurons as a function of stimulation intensity. This further corroborates that brain oscillations determine fluctuations in cortical excitability and establishes phase-triggered EEG-TMS as a sensitive tool to investigate the effects of brain oscillations on stimulus-related cortical dynamics.