Targeting motor cortex high-excitability states defined by functional connectivity with real-time EEG–TMS

We tested previous post-hoc findings indicating a relationship between functional connectivity (FC) in the motor network and corticospinal excitability (CsE), in a real-time EEG-TMS experiment in healthy participants. We hypothesized that high FC between left and right motor cortex predicts high CsE. FC was quantified in real-time by single-trial phase-locking value (stPLV), and TMS single pulses were delivered based on the current FC. CsE was indexed by motor-evoked potential (MEP) amplitude in a hand muscle. Possible confounding factors (pre-stimulus mu-power and phase, interstimulus interval) were evaluated post hoc. MEPs were significantly larger during high FC compared to low FC. Post hoc analysis revealed that the FC condition showed a significant interaction with mu-power in the stimulated hemisphere. Further, inter-stimulus interval (ISI) interacted with high vs. low FC conditions. In summary, FC was confirmed to be predictive of CsE, but should not be considered in isolation from mu-power and ISI. Moreover, FC was complementary to mu-phase in predicting CsE. Motor network FC is another marker of real-time accessible CsE beyond previously established markers, in particular phase and power of the mu rhythm, and may help define a more robust composite biomarker of high/low excitability states of human motor cortex.