Enhancing Gamma Oscillations Restores Primary Motor Cortex Plasticity in Parkinson's Disease

In humans, gamma oscillations in cortical motor areas reflect asynchronous synaptic activity and contribute to plasticity processes. In Parkinson's disease (PD), gamma oscillatory activity in the basal ganglia-thalamo-cortical network is altered and the LTP-like plasticity elicited by intermittent theta burst stimulation (iTBS) is reduced in the primary motor cortex (M1). In this study, we tested whether transcranial alternating current stimulation (tACS) delivered at gamma frequency promotes iTBS-induced LTP-like plasticity in Ml in PD patients. Sixteen patients (OFF condition) and 16 healthy subjects (HSs) underwent iTBS during gamma-tACS (iTBS-gamma tACS) and during sham-tACS (iTBS-sham tACS) in two sessions. Motor-evoked potentials (MEPs) evoked by single-pulse transcranial magnetic stimulation and short-interval intracortical inhibition (SICI) were recorded before and after the costimulation. A subgroup of patients also underwent iTBS during beta tACS. iTBS-sham tACS facilitated single-pulse MEPs in HSs, but not in patients. iTBS-gamma tACS induced a larger MEP facilitation than iTBS-sham tACS in both groups, with similar values in patients and HSs. In patients, SICI improved after iTBS-gamma tACS. The effect produced by iTBS-gamma tACS on single-pulse MEPs correlated with disease duration, while changes in SICI correlated with Unified Parkinson's Disease Rating Scale Part III scores. The effect of iTBS-beta tACS on both single-pulse MEPs and SICI was similar to that obtained in the iTBS-sham tACS session. Our data suggest that gamma oscillations have a role in the pathophysiology of the abnormal LTP-like plasticity in PD. Entraining MI neurons at the gamma rhythm through tACS may be an effective method to restore impaired plasticity.