Sensory Entrained TMS (seTMS) Enhances Motor Cortex Excitability

Abstract

Transcranial magnetic stimulation (TMS) applied to the motor cortex has revolutionized the study of motor physiology in humans. Despite this, TMS-evoked electrophysiological responses show significant fluctuation, due in part to inconsistencies between TMS pulse timing and ongoing brain oscillations. Small or inconsistent responses to TMS limit mechanistic insights and clinical efficacy, necessitating the development of methods to precisely coordinate the timing of TMS pulses to the phase of relevant oscillatory activity. We introduce Sensory Entrained TMS (seTMS), a novel approach that uses musical rhythms to synchronize brain oscillations and time TMS pulses to enhance cortical excitability. Focusing on the sensorimotor alpha rhythm, a neural oscillation associated with motor cortical inhibition, we examine whether rhythm-evoked sensorimotor alpha phase alignment affects primary motor cortical (M1) excitability in healthy young adults (n = 33). We first confirmed using electroencephalography (EEG) that passive listening to musical rhythms desynchronizes inhibitory sensorimotor brain rhythms (mu oscillations) around 200 ms before auditory rhythmic events (27 participants). We then targeted this optimal time window by delivering single TMS pulses over M1 200 ms before rhythmic auditory events while recording motor-evoked potentials (MEPs; 19 participants), which resulted in significantly larger MEPs compared to standard single pulse TMS and an auditory control condition. Neither EEG measures during passive listening nor seTMS-induced MEP enhancement showed dependence on musical experience or training. These findings demonstrate that seTMS effectively enhances corticomotor excitability and establishes a practical, cost-effective method for optimizing non-invasive brain stimulation outcomes.

Keywords: electroencephalogram (EEG); motor evoked potential (MEP); non‐invasive brain stimulation (NIBS); transcranial magnetic stimulation (TMS).

FIGURE 1

Study design and seTMS implementation. (A) Desynchronization of mu occurs prior to beat events in musical rhythms and represents a high excitability state. Highest excitability states occur ~200 ms prior to the musical beat events, regardless of musical tempo. (B) TMS pulses were applied to the primary motor cortex using standard single pulse (standard spTMS) and single pulse seTMS (at 200 ms prior to musical beat events). (C) Peak‐to‐peak amplitude of averaged motor‐evoked potentials (MEPs) from EMG of the FDI muscle was used to assess excitability. Interstimulus interval lengths between TMS pulses were matched between standard TMS and seTMS conditions, and at least 3 s long. Musical sounds were played through earbud‐earplugs and noise minimizing over‐the‐ear muffs were worn to reduce perception of TMS sounds.

FIGURE 2

Auditory rhythms desynchronize mu. (A) Individual participant music‐induced motor cortex phase coherence in alpha (mu) and beta bands, with maximal excitability (low alpha/higher beta) occurring approximately 200 ms before beat events. Averaged across three channels from over the motor cortex (C5, C3, C1). (B) Music‐induced phase coherence in n = 27 participants, with maximal excitability occurring approximately 200 ms before beat events. (C) Individual participant (n = 27) alpha ITC trough times (with Box and Whisker plot, alpha ITC peak times in gray, slopes from trough to peak in gray), and (D) alpha ITC at trough versus at peak (***t(26) = −8.34, p = 8.12 × 10⁻⁹).

FIGURE 3

seTMS increases the amplitude of motor‐evoked potentials compared with standard TMS and an auditory control condition. The auditory control condition used auditory matching to seTMS but with TMS pulses at 0 ms from the beat events. (A) Motor‐evoked potentials (MEPs) averaged over all participants (n = 19). Shading represents standard error. (B) Peak‐to‐peak amplitude mean (±standard error). Average percent increase from standard TMS = mean 77%, median 22% (**black t(18) = 3.78, p = 0.0014; gray t(18) = 3.73, p = 0.0015). (C) Individual participants.

FIGURE 4

ITC dynamics and seTMS effects do not depend on musical experience. (A) Individual participant ITC local minima (t(25) = −0.39, p = 0.70) and slopes (with group average slope shown using a thicker line) in musicians (n = 14) and non‐musicians (n = 13). (B) Individual participants' increase in MEP size with seTMS in musicians (n = 8) and nonmusicians (n = 11), shown as percent change from standard TMS (t(17) = 0.74, p = 0.47) and from the auditory control condition (t(17) = 0.88, p = 0.39).