title: Driving Human Motor Cortical Oscillations Leads to Behaviorally Relevant Changes in Local GABAAInhibition: 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 GABAAinhibition, as quantified by short interval intracortical inhibition. The magnitude of this effect was positively correlated with the magnitude of GABAAdecrease during movement preparation, when gamma activity in motor circuitry is known to increase. In addition, gamma tACS-induced change in GABAAinhibition was closely related to performance in a motor learning task such that subjects who demonstrated a greater increase in GABAAinhibition 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 STATEMENTGamma oscillations have a vital role in motor control. Using a combined tACS-TMS approach, we demonstrate that driving gamma frequency oscillations modulates GABAAinhibition in the human motor cortex. Moreover, there is a clear relationship between the change in magnitude of GABAAinhibition induced by tACS and the magnitude of GABAAinhibition 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.
authors.affiliation: Oxford Centre for fMRI of the Brain, Nuffield Department of Clinical Neurosciences, and magdalena.nowak@ndcn.ox.ac.uk.|Oxford Centre for Human Brain Activity, Department of Psychiatry, University of Oxford, Oxford OX3 7JX, United Kingdom.
authors.forename: Magdalena
authors.identifier: 0000-0001-6346-197X
authors.initials: M
authors.lastname: Nowak
authors.affiliation: Oxford Centre for fMRI of the Brain, Nuffield Department of Clinical Neurosciences, and.|Oxford Centre for Human Brain Activity, Department of Psychiatry, University of Oxford, Oxford OX3 7JX, United Kingdom.
authors.forename: Emily
authors.identifier: 0000-0001-6990-4540
authors.initials: E
authors.lastname: Hinson
authors.affiliation: Oxford Centre for Human Brain Activity, Department of Psychiatry, University of Oxford, Oxford OX3 7JX, United Kingdom.
authors.forename: Freek
authors.initials: F
authors.lastname: van Ede
authors.affiliation: Medical Research Council Brain Network Dynamics Unit and Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, United Kingdom.
authors.forename: Alek
authors.identifier: 0000-0003-4791-8153
authors.initials: A
authors.lastname: Pogosyan
authors.affiliation: Medical Research Council Brain Network Dynamics Unit and Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, United Kingdom.|Unit of Neurology, Neurophysiology, Neurobiology, Department of Medicine, University Campus Bio-Medico, 00128 Rome, Italy, and.|Department of Neurology and Psychiatry, Sapienza University of Rome, 00185 Rome, Italy.
authors.forename: Andrea
authors.identifier: 0000-0001-6601-4964
authors.initials: A
authors.lastname: Guerra
authors.affiliation: Oxford Centre for Human Brain Activity, Department of Psychiatry, University of Oxford, Oxford OX3 7JX, United Kingdom.
authors.forename: Andrew
authors.identifier: 0000-0003-2267-9897
authors.initials: A
authors.lastname: Quinn
authors.affiliation: Medical Research Council Brain Network Dynamics Unit and Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, United Kingdom.
authors.forename: Peter
authors.identifier: 0000-0002-5201-3044
authors.initials: P
authors.lastname: Brown
authors.affiliation: Oxford Centre for fMRI of the Brain, Nuffield Department of Clinical Neurosciences, and.|Oxford Centre for Human Brain Activity, Department of Psychiatry, University of Oxford, Oxford OX3 7JX, United Kingdom.
authors.forename: Charlotte J
authors.identifier: 0000-0002-5542-5036
authors.initials: CJ
authors.lastname: Stagg
mesh_terms: D000328:Adult; D001519:Behavior / Q000502:physiology*; D018592:Cross-Over Studies; D004576:Electromyography; D019054:Evoked Potentials, Motor / Q000502:physiology; D005260:Female; D006801:Humans; D007395:Interneurons / Q000502:physiology; D007858:Learning / Q000502:physiology; D015225:Magnetoencephalography; D008297:Male; D009044:Motor Cortex / Q000502:physiology*; D011597:Psychomotor Performance / Q000502:physiology; D011930:Reaction Time / Q000502:physiology; D011963:Receptors, GABA-A / Q000502:physiology*; D065908:Transcranial Direct Current Stimulation; D050781:Transcranial Magnetic Stimulation; D055815:Young Adult
chemical_list: D011963:Receptors, GABA-A
keywords: GABA inhibition; concurrent tACS and TMS; gamma oscillations; motor excitability; motor learning; tACS