Phase synchronicity of μ-rhythm determines efficacy of interhemispheric communication between human motor cortices

The theory of communication through coherence predicts that effective connectivity between nodes in a distributed oscillating neuronal network depends on their instantaneous excitability state and phase synchronicity (Fries, 2005). Here, we tested this prediction by using state-dependent millisecond-resolved real-time electroencephalography-triggered dual-coil transcranial magnetic stimulation (EEG-TMS) (Zrenner et al., 2018) to target the EEG-negative (high-excitability state) versus EEG-positive peak (low-excitability state) of the sensorimotor μ-rhythm in the left (conditioning) and right (test) motor cortex (M1) of 16 healthy human subjects (9 female, 7 male). Effective connectivity was tested by short-interval interhemispheric inhibition (SIHI); that is, the inhibitory effect of the conditioning TMS pulse given 10–12 ms before the test pulse on the test motor-evoked potential. We compared the four possible combinations of excitability states (negative peak, positive peak) and phase relations (in-phase, out-of-phase) of the μ-rhythm in the conditioning and test M1 and a random phase condition. Strongest SIHI was found when the two M1 were in phase for the high-excitability state (negative peak of the μ-rhythm), whereas the weakest SIHI occurred when they were out of phase and the conditioning M1 was in the low-excitability state (positive peak). Phase synchronicity contributed significantly to SIHI variation, with stronger SIHI in the in-phase than out-of-phase conditions. These findings are in exact accord with the predictions of the theory of communication through coherence. They open a translational route for highly effective modification of brain connections by repetitive stimulation at instants in time when nodes in the network are phase synchronized and excitable.