Phase Synchronicity of μ-Rhythm Determines Efficacy of Interhemispheric Communication Between Human Motor Cortices

Abstract

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-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-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-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-ofphase 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.

Pulsed Facilitation of Corticospinal Excitability by the Sensorimotor μ-Alpha Rhythm

“…The resulting net facilitation of corticospinal excitability during the asymmetric -alpha oscillation corroborates recent findings of a weak positive relationship between -alpha power and MEP amplitude (Hussain et al, 2018;Thies et al, 2018;Ogata et al, 2019). While the larger excitability for troughs than peaks replicates previous findings (Schaworonkow et al, 2018(Schaworonkow et al, , 2019Stefanou et al, 2018;Zrenner et al, 2018), periods of spontaneous -alpha desynchronization (low power trials) had not yet been considered as baseline to determine the direction of phasic modulation. The only other study taking pre-TMS -alpha power into account used post hoc trial sorting of peaks and troughs and a trial-by-trial linear mixed-effects model to include continuous power values (Hussain et al, 2018).…”

“…In the primary motor cortex (M1), earlier studies either observed negative relationships in small samples (Zarkowski et al, 2006;Lepage et al, 2008;Sauseng et al, 2009), or no relationship at all (for review, see Madsen et al, 2019), whereas more recent studies suggest a positive linear relationship with motor evoked potential (MEP) amplitude (Hussain et al, 2018;Thies et al, 2018;Ogata et al, 2019). Our group previously observed -alpha phase to modulate corticospinal excitability, with larger MEPs evoked during troughs compared with peaks of -alpha waves (Schaworonkow et al, 2018(Schaworonkow et al, , 2019Stefanou et al, 2018;Zrenner et al, 2018). However, it remained unknown whether this phasic modulation reflects asymmetric pulsed inhibition, asymmetric pulsed facilitation, or a symmetric combination of both (Fig.…”

No trace of phase: Corticomotor excitability is not tuned by phase of pericentral mu-rhythm

“…Three recent studies, all performed by the same group also used a brain-state triggered EEG-TMS setup to investigate the influence of mu-phase on MEP amplitude [33][34][35]. In contrast with our negative findings, these studies showed significantly larger MEP amplitudes when TMS was given in the trough compared to the peak of the mu-oscillation.…”

“…EEGinformed phase-dependent TMS was first applied during non-REM sleep [32] and recently applied during resting wakefulness. In highly pre-selected groups of healthy individuals with strong pericentral mu-activity, single-pulse TMS was applied to M1-HAND dependent on mu-phase [33][34][35] or mu-power [36] of the locally expressed mu-activity. These studies found higher MEP amplitudes at the trough relative to the peak of the mu-phase [33,34] as well as higher MEP amplitude in epochs with high relative to low mu-power [36], while no interaction between the two was reported.…”

Concurrent human TMS-EEG-fMRI enables monitoring of oscillatory brain state-dependent gating of cortico-subcortical network activity

“…In the same frequency-band as parietal alpha, several studies have investigated the influence of mu-phase in motor cortex on motor evoked potential (MEP) amplitude with an EEG-TMS setup. Larger MEP amplitudes were found when TMS was administered at the trough compared to when it was administered at the peak of the mu-oscillation [31][32][33] (but see ref. 34 ).…”