L-dopa treatment increases oscillatory power in the motor cortex of Parkinson's disease patients

Abstract

Parkinson's disease (PD) is a movement disorder caused by dopaminergic neurodegeneration. Levodopa (L-dopa) is an effective medication for alleviating motor symptoms in PD that has been shown previously to reduce subcortical beta (13-30 Hz) oscillations. How L-dopa influences oscillations in the motor cortex is unclear. In this study, 21 PD patients were recorded with magnetoencephalography (MEG) in L-dopa ON and OFF states. Oscillatory components of resting-state power spectra were compared between the two states and the significant effect was localized using beamforming. Unified Parkinson's Disease Rating Scale (UPDRS) III akinesia and rigidity sub-scores for the most affected hemibody were correlated with source power values for the contralateral hemisphere. An L-dopa-induced power increase was found over the central sensors significant in the 18-30 Hz range (F_(1,20) > 14.8, P_{FWE corr} < 0.05, cluster size inference with P = 0.001 cluster-forming threshold). Beamforming localization of this effect revealed distinct peaks at the bilateral sensorimotor cortex. A significant correlation between the magnitude of L-dopa induced 18-30 Hz oscillatory motor-cortical power increase and the degree of improvement in contralateral akinesia and rigidity was found (F_{(2, 19)} = 4.9, p_one-tailed = 0.02, R² = 0.2). Power in the same range was also inversely correlated with combined akinesia and rigidity scores in the L-dopa OFF state (F_{(2, 19)} = 9.2, p_two-tailed = 0.007, R² = 0.33) but not in the L-dopa ON state (F_{(2, 19)} = 0.27, p_two-tailed = 0.6, R² = 0.01). These results suggest that the role of motor cortical beta oscillations in PD is distinct from that of subcortical beta.

Keywords: Cortex; Dopamine; Human; M1; Movement disorders.

Fig. 1

L-dopa significantly alleviated the motor symptoms of PD patients. The asterisks indicate p < 0.0001 in a paired t-test. The improvement in UPDRS III was 55% in total score, 54% in akinesia, 53% in rigidity and 93% in tremor.

Fig. 2

L-dopa increased the beta power in the motor cortex of PD patients. (A). Sensor-level scalp x frequency comparison of MEG power between the ON and OFF states. L-dopa induced significant power increase over the central sensors in the 18–30 Hz range (peak at 24 Hz, P_{FWE corr} < 0.05 at the cluster-level with cluster-forming threshold p < 0.001). The letters indicate directions to aid interpretation of the map (A-anterior, P-posterior, L-left, R-right) (B). DICS beamforming localization focusing on the significant frequency band revealed distinct power peaks in the bilateral sensorimotor cortex (P_uncorr < 0.01). The right side showed a peak at Montreal Neurological Institute (MNI) coordinates 36 −22 62 corresponding to Brodmann area (BA) 4. The left side showed a peak at −34 −20 68 corresponding to BA6.

Fig. 3

(A). The individual peaks of the ON-OFF difference images used for virtual electrode source extraction. The group peaks are shown with large gray circles. (B). Oscillatory components of the log-power spectra (after subtraction of the non-oscillatory component estimated with the FOOOF algorithm) averaged across hemispheres for the two L-dopa states and their difference. The difference curve is shown with 95% confidence intervals. The shaded area corresponds to the 18–30 Hz range for which a significant effect was found at the sensor level.

Fig. 4

Correlations of the source-level beta power with combined akinesia/rigidity in PD patients. These correlations were computed for the most affected hemibody and the contralateral hemisphere. (A). Significant correlation of 18–30 Hz oscillatory log-power with the contralateral akinesia + rigidity scores in the OFF state (F_{(2, 19)} = 9.2, P_two-tailed = 0.007, R² = 0.33). (B). Significant correlation of ON-OFF difference in 18–30 Hz oscillatory log-power with OFF-ON difference in akinesia + rigidity (F_{(2, 19)} = 4.9, P_one-tailed = 0.02, R² = 0.2).