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Key points• Parkinson's disease (PD) is a common movement disorder due to dopaminergic denervation of the basal ganglia. It is characterized by exaggerated oscillatory activity within central motor-control loops, while cerebro-muscular coherence is reduced at frequencies below 30 Hz.• So far, studies investigating the neurophysiological alterations of PD have focused on patients with advanced PD. It remains open to what extent changes of oscillatory activity might occur at early disease stages, representing a characteristic feature of the disease.• Using magnetoencephalography we show that cerebro-muscular coherence is unaffected in early PD while beta band oscillations of bilateral primary sensori-motor cortices are already increased at the earliest stages of PD and, as the disease progresses, evolve a hemispheric imbalance associated with movement execution.Abstract Pathophysiological changes in basal ganglia-thalamo-cortical circuits are well established in idiopathic Parkinson's disease (PD). However, it remains open whether such alterations already occur at early stages representing a characteristic neurophysiological marker of PD. Therefore, the present study aims at elucidating changes of synchronised oscillatory activity in early PD patients. In this study, we performed whole-head magnetoencephalography (MEG) in a resting condition and during steady state contraction of the more severely affected forearm in 10 drug-naive, de novo patients, in 10 early-stage patients with chronic medication and in 10 age-matched control subjects. While cortico-muscular coherence (CMC) did not differ between groups, patients showed increased sensori-motor cortical power at beta frequency (13-30 Hz) during rest as well as during isometric contraction compared to controls. In healthy control subjects the power of the contralateral hemisphere was significantly suppressed during isometric contraction. By contrast, both hemispheres were activated equally strongly in de novo patients. In medicated patients, the pattern was found to be reversed. Contralateral beta power was significantly correlated with motor impairment during isometric contraction but not during rest.The present results suggest that the reduced ability of the primary motor cortex to disengage from increased beta band oscillations during the execution of movements is an early marker of PD.

Parkinson’s disease (PD) is associated with pathologically altered oscillatory activity. While synchronized oscillations between 13 and 30 Hz are increased within a cortico-subcortical network, cortico-muscular coupling (CMC) is decreased. The present study aims at investigating the effect of non-invasive transcranial alternating current stimulation (tACS) of the primary motor cortex (M1) on motor symptoms and motor-cortical oscillations in PD. In 10 PD patients and 10 healthy control subjects, static isometric contraction, dynamic fast finger tapping, and diadochokinesia of the more severely affected hand were investigated prior to and shortly after tACS of the contralateral M1 at 10 Hz vs. 20 Hz vs. sham. During isometric contraction, neuromagnetic activity was recorded using magnetoencephalography. 20 Hz tACS attenuated beta band CMC during isometric contraction and amplitude variability during finger tapping in PD patients but not in healthy control subjects. 10 Hz tACS yielded no significant after-effects. The present data suggest that PD is associated with pathophysiological alterations which abet a higher responsiveness toward frequency-specific tACS – possibly due to pathologically altered motor-cortical oscillatory synchronization at frequencies between 13 and 30 Hz.

Synchronous oscillatory activity at alpha (8–12 Hz), beta (13–30 Hz), and gamma (30–90 Hz) frequencies is assumed to play a key role for motor control. Corticomuscular coherence (CMC) represents an established measure of the pyramidal system's integrity. Transcranial alternating current stimulation (tACS) offers the possibility to modulate ongoing oscillatory activity. Behaviorally, 20 Hz tACS in healthy subjects has been shown to result in movement slowing. However, the neurophysiological changes underlying these effects are not entirely understood yet. The present study aimed at ascertaining the effects of tACS at 10 and 20 Hz in healthy subjects on CMC and local power of the primary sensorimotor cortex. Neuromagnetic activity was recorded during isometric contraction before and at two time points (2–10 min and 30–38 min) after tACS of the left primary motor cortex (M1), using a 306 channel whole head magnetoencephalography (MEG) system. Additionally, electromyography (EMG) of the right extensor digitorum communis (EDC) muscle was measured. TACS was applied at 10 and 20 Hz, respectively, for 10 min at 1 mA. Sham stimulation served as control condition. The data suggest that 10 Hz tACS significantly reduced low gamma band CMC during isometric contraction. This implies that tACS does not necessarily cause effects at stimulation frequency. Rather, the findings suggest cross-frequency interplay between alpha and low gamma band activity modulating functional interaction between motor cortex and muscle.