Phase Dependency of the Human Primary Motor Cortex and Cholinergic Inhibition Cancelation During Beta tACS

Abstract

The human motor cortex has a tendency to resonant activity at about 20 Hz so stimulation should more readily entrain neuronal populations at this frequency. We investigated whether and how different interneuronal circuits contribute to such resonance by using transcranial magnetic stimulation (TMS) during transcranial alternating current stimulation (tACS) at motor (20 Hz) and a nonmotor resonance frequency (7 Hz). We tested different TMS interneuronal protocols and triggered TMS pulses at different tACS phases. The effect of cholinergic short-latency afferent inhibition (SAI) was abolished by 20 Hz tACS, linking cortical beta activity to sensorimotor integration. However, this effect occurred regardless of the tACS phase. In contrast, 20 Hz tACS selectively modulated MEP size according to the phase of tACS during single pulse, GABAAergic short-interval intracortical inhibition (SICI) and glutamatergic intracortical facilitation (ICF). For SICI this phase effect was more marked during 20 Hz stimulation. Phase modulation of SICI also depended on whether or not spontaneous beta activity occurred at ~20 Hz, supporting an interaction effect between tACS and underlying circuit resonances. The present study provides in vivo evidence linking cortical beta activity to sensorimotor integration, and for beta oscillations in motor cortex being promoted by resonance in GABAAergic interneuronal circuits.

Phase-specific microstimulation in brain machine interface setting differentially modulates beta oscillations and affects behavior

“…Careful choice of a specific stimulation phase could therefore induce opposite perturbations, enhancing an existing oscillation or alternatively, suppressing the oscillation. This notion is supported by recent computational (Holt et al, 2016), experimental (optogenetic stimulation (Siegle and Wilson, 2014) and transcranial magnetic stimulation (Guerra et al, 2016;Schilberg et al, 2018)) and clinical studies (deep brain stimulation (DBS) locked to the patient's tremor (Cagnan et al, 2017)). A recent study conducted on Parkinson's disease patients used open-loop deep brain stimulation, and applied offline analysis to demonstrate that the suppression of Beta was dependent on the phase relations between the electrical pulse and the neuronal oscillations (Holt et al, 2019).…”

Guiding transcranial brain stimulation by EEG/MEG to interact with ongoing brain activity and associated functions: A position paper

“…In terms of immediate effects during NTBS, there are multiple examples that this approach may indeed lend itself for a targeted intervention into oscillatory brain activity through entrainment that can affect brain function and behavior, both using TMS or TACS (for TMS examples see, Klimesch et al, 2003, Sauseng et al, 2009b, Romei et al, 2010, 2015, Thut et al, 2011, Chanes et al, 2013, Chanes et al, 2015, Hanslmayr et al, 2014, Ruzzoli and Soto-Faraco, 2014, Jaegle and Ro, 2014, Quentin et al, 2015a; Quentin et al, 2015b; for TACS examples see, Pogosyan et al, 2009, Feurra et al, 2011, Joundi et al, 2012, Neuling et al, 2012, Santarnecchi et al, 2013, Helfrich et al, 2014b, Cecere et al, 2015, Witkowski et al, 2015, Chander et al, 2016, Ruhnau et al, 2016, Guerra et al, 2016). However, most of the evidence for the existence of entrainment effects comes from behavioral studies.…”

“…over sensory areas) (Neuling et al, 2012). Similarly, TMS-probed excitability in intracortical circuits as inferred from paired-pulse designs (Hallett, 2007) shows modulation by TACS in a frequency- and phase-specific manner, both in terms of intracortical facilitation (ICF) and short-interval intracortical inhibition (SICI) (Guerra et al, 2016). Some level of entrainment seems to have modulated task performance and cortical excitability in-line with TACS phase, as suggested by these behavioral data.…”

Phase-specific manipulation of neural oscillatory activity by transcranial alternating current stimulation

“…For instance, tACS applied in the alpha and beta range was shown to lead to cyclic modulation of auditory, somatosensory or visual stimulus perception (20)(21)(22)(23). Further insight has been provided primarily in the motor domain, by showing tACS-phase-dependent changes in cortical excitability as measured by concurrent motor evoked potentials (24)(25)(26) or tACSinduced enhancement and phase cancellation of peripheral tremor in healthy subjects and patients with Parkinson's disease using closed-loop protocols (27)(28)(29)(30). Yet, latest findings by Asamoah et al (31) revealed that tACS-effects on the motor cortex are dominated by cutaneous stimulation of peripheral nerves in the skin leading to rhythmic activation of the sensorimotor system rather than by transcranial modulation of cortical tissue.…”