Motor-cortical oscillations in early stages of Parkinson's disease

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.

Figures

Figure 1. Mean UPDRS III scores of participating patients and control subjects as a measure of motor impairment

Error bars indicate standard error of the mean (SEM).

Figure 2. Analysis of MEG spectral power during isometric contraction

A, power averaged across sensors covering S1/M1 contra- and ipsilateral to isometric contraction in one control subject. Note that power of the hemisphere contralateral to isometric contraction is suppressed at frequencies below 30 Hz as compared to the ipsilateral side. B, mean power of ipsi- and contralateral S1/M1 in medicated and de novo patients and control subjects at beta frequency. Power was estimated by logarithmic transformation. Error bars indicate SEM.

Figure 3. Correlation between S1/M1 power contralateral to isometric contraction at beta frequency and UPDRS III

During isometric contraction S1/M1 power at beta frequency is significantly correlated with UPDRS III as a measure of motor impairment. Please note that power values from two control subjects (UPDRS III = 0) show a strong overlap. The lowest data point actually represents data from two control subjects.

Figure 4. Mean S1/M1 power amplitudes at beta frequency during rest

Power was estimated by logarithmic transformation. Note that the terms ipsi- and contralateral refer to the more severely affected hand. Error bars indicate SEM. In contrast to isometric contraction, no significant hemisphere×group interaction was evident.

Figure 5. Cortico-muscular coherence at beta frequency

A, example of localization of CMC in one control subject during isometric contraction with the left hand in the contralateral primary motor cortex (Brodmann area 4). B, group statistics did not reveal significant differences between groups. Presented are mean values. Error bars indicate SEM.

Figure 6. Analysis of EMG spectral power during isometric contraction

A, the spectrum of one characteristic control subject. Discernible peaks at alpha (8–12 Hz), beta (13–30 Hz) and low gamma (30–60 Hz) frequencies were evident. B, while power amplitude did not differ between groups at any of these frequencies, a shift towards lower frequencies was found in medicated patients in the beta range. Shown are mean frequency values. Error bars indicate SEM.