Driving Human Motor Cortical Oscillations Leads to Behaviorally Relevant Changes in Local GABA_AInhibition: A tACS-TMS Study

Abstract

Beta and gamma oscillations are the dominant oscillatory activity in the human motor cortex (M1). However, their physiological basis and precise functional significance remain poorly understood. Here, we used transcranial magnetic stimulation (TMS) to examine the physiological basis and behavioral relevance of driving beta and gamma oscillatory activity in the human M1 using transcranial alternating current stimulation (tACS). tACS was applied using a sham-controlled crossover design at individualized intensity for 20 min and TMS was performed at rest (before, during, and after tACS) and during movement preparation (before and after tACS). We demonstrated that driving gamma frequency oscillations using tACS led to a significant, duration-dependent decrease in local resting-state GABAA inhibition, as quantified by short interval intracortical inhibition. The magnitude of this effect was positively correlated with the magnitude of GABAA decrease during movement preparation, when gamma activity in motor circuitry is known to increase. In addition, gamma tACS-induced change in GABAA inhibition was closely related to performance in a motor learning task such that subjects who demonstrated a greater increase in GABAA inhibition also showed faster short-term learning. The findings presented here contribute to our understanding of the neurophysiological basis of motor rhythms and suggest that tACS may have similar physiological effects to endogenously driven local oscillatory activity. Moreover, the ability to modulate local interneuronal circuits by tACS in a behaviorally relevant manner provides a basis for tACS as a putative therapeutic intervention.SIGNIFICANCE STATEMENT Gamma oscillations have a vital role in motor control. Using a combined tACS-TMS approach, we demonstrate that driving gamma frequency oscillations modulates GABAA inhibition in the human motor cortex. Moreover, there is a clear relationship between the change in magnitude of GABAA inhibition induced by tACS and the magnitude of GABAA inhibition observed during task-related synchronization of oscillations in inhibitory interneuronal circuits, supporting the hypothesis that tACS engages endogenous oscillatory circuits. We also show that an individual's physiological response to tACS is closely related to their ability to learn a motor task. These findings contribute to our understanding of the neurophysiological basis of motor rhythms and their behavioral relevance and offer the possibility of developing tACS as a therapeutic tool.

Phase of beta-frequency tACS over primary motor cortex modulates corticospinal excitability

“…We did not observe a modulatory effect on MEPs during or after tACS-TMS stimulation. This finding is in line with other studies reporting no modulatory effects on MEPs during or after tACS over M1 at (individual) beta or other frequencies (Antal et al, 2008;Nowak et al, 2017;Wach et al, 2013). In contrast, yet other studies have reported such modulatory effects (Feurra et al, 2011(Feurra et al, , 2013Schutter & Hortensius, 2011), however their design differed to that of the current study.…”

Effects of beta-tACS on corticospinal excitability: A meta-analysis

“…It has been suggested that these after effects depend on spike-timing dependent plasticity (STDP), which may be induced by tACS in recurrent M1 networks. However, others have found no beta-tACS induced after effects [21,26].…”

“…TACS studies have tested the idea that entrainment of beta oscillations affects neural excitability by measuring motor-evoked potentials (MEP) with single pulse transcranial magnetic stimulation (TMS). Whereas several studies have demonstrated increased MEP amplitudes during beta-tACS [16e20], others have found no effects [21], and in some cases even decreases in MEP amplitudes were found [22]. In addition to online effects, it has recently been suggested that tACS may induce M1 plasticity lasting up to 60 min after intervention [20,23e25].…”

Intervention-Induced Changes in Cortical Connectivity and Activity in Severe Chronic Hemiparetic Stroke

“…In healthy controls, gamma band power increases in contralateral primary sensorimotor cortex just before the onset and during movement [37][38][39][40][41][42] . This increase in gamma power has been shown to facilitate movement in studies using transcranial alternation current stimulation (tACS) to artificially increase gamma power over the contralateral primary sensorimotor cortex [43][44][45] .…”

“…Typically, gamma is associated with local intracortical processing, particularly within GABAergic interneuronal circuits 14,15 , with increases in gamma power related to movement associated with decreases in GABAA 44 . However, gamma synchronization is notable usually confined to a small area in the contralateral primary sensorimotor cortex in healthy controls 37,40,46 , rather than bilateral increases in gamma during movement as observed here prior to the intervention.…”