The phase of sensorimotor mu and beta oscillations has the opposite effect on corticospinal excitability

Abstract

Neural oscillations in the primary motor cortex (M1) shape corticospinal excitability. Power and phase of ongoing mu (8-13 Hz) and beta (14-30 Hz) activity may mediate motor cortical output. However, the functional dynamics of both mu and beta phase and power relationships and their interaction, are largely unknown. Here, we employ recently developed real-time targeting of the mu and beta rhythm, to apply phase-specific brain stimulation and probe motor corticospinal excitability non-invasively. For this, we used instantaneous read-out and analysis of ongoing oscillations, targeting four different phases (0, 90, 180, and 270 degrees) of mu and beta rhythms with suprathreshold single-pulse transcranial magnetic stimulation (TMS) to M1. Ensuing motor evoked potentials (MEPs) in the right first dorsal interossei muscle were recorded. Twenty healthy adults took part in this double-blind randomized crossover study. Mixed model regression analyses showed significant phase-dependent modulation of corticospinal output by both mu and beta rhythm. Strikingly, these modulations exhibit a double dissociation. MEPs are larger at the mu trough and rising phase and smaller at the peak and falling phase. For the beta rhythm we found the opposite behavior. Also, mu power, but not beta power, was positively correlated with corticospinal output. Power and phase effects did not interact for either rhythm, suggesting independence between these aspects of oscillations. Our results provide insights into real-time motor cortical oscillation dynamics, which offers the opportunity to improve the effectiveness of TMS by specifically targeting different frequency bands.

Mu-Transcranial Alternating Current Stimulation Induces Phasic Entrainment and Plastic Facilitation of Corticospinal Excitability

“…Regarding the aftereffects of the µ-tACS paradigm on CSE, we observed significant increases in mean MEP amplitude from pre- to post-tACS for both the FDI (43.3% increase) and ADM (50% increase), in line with recent µ-tACS studies (Feurra et al, 2019; Fresnoza et al, 2018; Madsen et al, 2019a) and thus, supporting a facilitatory effect of µ oscillations on CSE (Bergmann et al, 2019; Karabanov et al, 2021; Ogata et al, 2019; Thies et al, 2018; Wischnewski et al, 2022). The response rate for this facilitatory effect was also relative;y consistent across participants, with 11 of the 13 participants demonstrating an increase in MEP amplitude (∼85% response rate), which represents, to our knowledge, the most effective means of increasing CSE across the multitude of plasticity-inducing paradigms currently in use (López-Alonso et al, 2014; Pellegrini et al, 2018; Veniero et al, 2015).…”

“…Mu (µ) oscillations (8–13 Hz) are one of the most prominent rhythms in the sensorimotor cortex during resting wake (Craddock et al, 2017; Hari, 2006; Weisz et al, 2014; Zhang and Ding, 2010) and are proposed to modulate CSE in a phase-specific manner (Baur et al, 2020; Berger et al, 2014; Bergmann et al, 2019; Hussain et al, 2018; Schaworonkow et al, 2018; Schaworonkow et al, 2019; Stefanou et al, 2018; Wischnewski et al, 2022; Zrenner et al, 2018;), with µ troughs thought to reflect active facilitation of gamma activity and information processing, referred to as the “pulsed facilitation” hypothesis (Bergmann et al, 2019). However, these troughs may instead reflect “pulsed inhibition” (akin to occipital alpha oscillations; Mathewson et al, 2011; Mazaheri and Jensen, 2010; Schalk, 2015) of the primary somatosensory cortex (S1) that results in a net transient local disinhibition of feed-forward inhibitory inputs from S1 to the primary motor cortex (M1; Bergmann et al, 2019; Murray and Keller, 2011; Thies et al, 2018; Turco et al, 2018).…”

“…Whilst the number of studies assessing the effects of µ-tACS on CSE are limited, recent studies report a facilitation of MEP amplitudes from µ-tACS (Feurra et al, 2019; Fresnoza et al, 2018; Madsen et al, 2019), supporting a facilitatory role of µ oscillations on CSE (Bergmann et al, 2019; Karabanov et al, 2021; Ogata et al, 2019; Thies et al, 2018; Wischnewski et al, 2022), whether that be via active facilitation of M1 or active inhibition of S1 to disinhibit M1. However only one of these studies (Madsen et al, 2019) assessed the relationship between µ-tACS phase and CSE, finding no effect of phase on CSE.…”

Alpha closed-loop auditory stimulation modulates waking alpha oscillations and sleep onset dynamics in a phase-dependent manner in humans

“…Indeed, closed-loop neuromodulation studies, in which stimulation parameters are adapted to the dynamics of the brain in real-time, have exploited the phase of some oscillations to do just that. For example, closed-loop phase-locked TMS studies have shown that the magnitude of TMS-induced muscle-evoked-potentials is dependent on the instantaneous phase of the rhythms of the motor cortex, such as the mu and/or beta rhythms [22][23][24][25] . Similarly, transcranial alternating current stimulation (TACS) matching the frequency and phase of slow oscillations during sleep has been shown to enhance these oscillations and impact overnight memory consolidation 26 .…”

Dissociation of direct and peripheral transcranial magnetic stimulation effects in nonhuman primates

“…In human research, TMS physiological effects can be measured non-invasively through motorevoked potentials [5][6][7] , functional magnetic resonance imaging [8][9][10] , and electroencephalography (EEG) [11][12][13][14][15][16] . Combined TMS-EEG is a promising method to study neural population responses to TMS with high temporal accuracy.…”