Brain-State-Resolved Consistency of Corticospinal Responses to TMS

An important feature of motor-evoked potential (MEP) responses to transcranial magnetic stimulation (TMS) over the primary motor cortex (M1) is their substantial trial-to-trial variability. Ongoing brain activity at the time of TMS, such as the power and phase of the sensorimotor mu rhythm, influences MEP amplitude. It is unclear to what extent these endogenous brain states also shape the consistency of MEP amplitude across trials.

We investigated trial-to-trial variability of MEP amplitude as a function of pre-stimulus mu dynamics.

Twenty-nine healthy participants received 1200 single TMS pulses over the left M1 during simultaneous electroencephalography (EEG) recording; 10 participants completed two sessions to assess inter-session reproducibility. Trials were stratified based on pre-stimulus mu power, phase, and interhemispheric M1-M1 functional connectivity. Brain-state-resolved MEP variability was quantified using the coefficient of variation (CV) within subsets of trials defined by similar pre-stimulus mu dynamics.

Trial subsets characterized by high mu power were associated with reduced MEP variability, indicating more consistent corticospinal output. In contrast, mu phase did not significantly influence MEP variability at the group level. Mu power group-level effects were reproducible across sessions in an exploratory test-retest analysis and across experimental sites.

We show that inter-trial consistency of MEP amplitude reflects a structured, brain-state-dependent feature of the sensorimotor network. These findings contribute to our mechanistic understanding of trial-to-trial variability in TMS-evoked responses. This may provide a basis for future TMS approaches aimed at reducing response variability and improving the consistency of neuromodulatory effects.