TMS-induced Phase Resets Depend on TMS Intensity and EEG Phase

. The phase of the electroencephalographic (EEG) signal predicts performance in motor, somatosensory, and cognitive functions. Studies suggest that brain phase resets align neural oscillations with external stimuli, or couple oscillations across frequency bands and brain regions. Transcranial Magnetic Stimulation (TMS) can cause phase resets noninvasively in the cortex, thus providing the potential to control phase-sensitive cognitive functions. However, the relationship between TMS parameters and phase resetting is not fully understood. This is especially true of TMS intensity, which may be crucial to enabling precise control over the amount of phase resetting that is induced. Additionally, TMS phase resetting may interact with the instantaneous phase of the brain. Understanding these relationships is crucial to the development of more powerful and controllable stimulation protocols.To test these relationships, we conducted a TMS-EEG study. We applied single-pulse TMS at varying degrees of stimulation intensity to the motor area in an open loop. Offline, we used an autoregressive algorithm to estimate the phase of the intrinsic-Alpha rhythm of the motor cortex at the moment each TMS pulse was delivered.. We identified post-stimulation epochs where-Alpha phase resetting and N100 amplitude depend parametrically on TMS intensity and are significantperipheral auditory sham stimulation. We observed-Alpha phase inversion after stimulations near peaks but not troughs in the endogenous-Alpha rhythm.. These data suggest that low-intensity TMS primarily resets existing oscillations, while at higher intensities TMS may activate previously silent neurons, but only when endogenous oscillations are near the peak phase. These data can guide future studies that seek to induce phase resetting, and point to a way to manipulate the phase resetting effect of TMS by varying only the timing of the pulse with respect to ongoing brain activity.