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

In humans, c oscillations in cortical motor areas reflect asynchronous synaptic activity and contribute to plasticity processes. In Parkinson’s disease (PD), c 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 c frequency promotes iTBS-induced LTP-like plasticity in M1 in PD patients. Sixteen patients (OFF condition) and 16 healthy subjects (HSs) underwent iTBS during c-tACS (iTBS-c 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 b tACS. iTBS-sham tACS facilitated single-pulse MEPs in HSs, but not in patients. iTBS-c 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-c tACS. The effect produced by iTBS-c 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-b tACS on both single-pulse MEPs and SICI was similar to that obtained in the iTBS-sham tACS session. Our data suggest that c oscillations have a role in the pathophysiology of the abnormal LTP-like plasticity in PD. Entraining M1 neurons at the c rhythm through tACS may be an effective method to restore impaired plasticity.