The functional role of theta-gamma oscillations in healthy human motor learning using theta-gamma phase amplitude coupling tACS

Abstract Background: Neuronal oscillations across frequency bands interact through cross‐frequency coupling (CFC) to support a range of computations across the brain. Of particular interest is the phase‐amplitude coupling (PAC) of theta (θ) and gamma (γ), where the amplitude of the high‐frequency gamma oscillation is modulated by the phase of the low‐frequency theta rhythm. θγ‐PAC is well‐described as a central mechanism of hippocampal‐dependent learning and has recently been demonstrated to play a key role in non‐hippocampal dependent learning tasks, specifically in the motor domain. It has therefore been suggested that θγ‐PAC may represent an emergent neural signature of plasticity and learning across the brain. Objective: Using transcranial Alternating Current Stimulation (tACS) we aim to causally demonstrate the role of θγ‐PAC on novel motor skill acquisition in healthy humans. Methods: This double‐blind, sham‐controlled, parallel design study assesses the role of θγ‐PAC tACS on the acquisition of a new motor skill in 90, healthy, right‐handed participants aged 18‐35. Two 5x5cm2 rubber transcranial electrical stimulation electrodes are centred over the left primary motor cortex (C3) and the parietal vertex (Pz). Custom‐coded 2mA (peak‐to‐peak) θγ‐PAC waveforms (6Hz/75Hz and 6Hz/45Hz) are delivered via a Nurostym, time‐locked to the onset of movement. The motor task involves tracing a stationary three‐peak sinusoid wave using a pinchmeter with the dominant hand. Results: Participants are able to accurately learn the novel motor task, as indexed via a reduction in tracing error over time. At the time of abstract submission, we are currently still blinded to the underlying effects of stimulation. Conclusion: The present study investigates whether θγ‐PAC plays a critical role in healthy human motor control, using tACS over human primary motor cortex. Research Category and Technology and Methods Translational Research: 8. Transcranial Alternating Current Stimulation (tACS) Keywords: Neuromodulation, Motor learning, Theta‐gamma, GABA