Distinct medication-state modulation of motor-cortical low-beta power in tremor-dominant and postural...

Source-space electroencephalography (EEG) provides a noninvasive approach for probing oscillatory activity in motor-cortical and cerebellar networks in Parkinson's disease (PD). However, electrophysiological evidence differentiating tremor-dominant (TD) and postural instability/gait difficulty (PIGD) subtypes under a harmonized medication OFF/ON protocol remains limited. We therefore examined whether TD and PIGD differ in medication-state modulation of motor-cortical low-beta power and cerebellum-related connectivity using 64-channel resting-state source-space EEG.

We prospectively enrolled 12 healthy controls, 20 patients with PIGD, and 18 with TD. In a fixed OFF-to-ON sequence, participants underwent 64-channel eyes-closed resting-state EEG. Source-space power spectral density (PSD) and weighted phase lag index (wPLI) were computed for prespecified motor-cortical and cerebellar regions of interest. Primary effects were tested with linear mixed-effects models. Exploratory edge-wise analyses were controlled using the Benjamini-Hochberg false discovery rate (BH-FDR), and network-level effects were assessed with network-based statistics (NBS).

For the prespecified primary PSD endpoint, low-beta relative PSD in the primary motor cortex (M1) showed a significant group × state interaction (χ²(1) = 5.84, p = 0.016; β = -1.45 dB, 95% CI [-2.59, -0.32]). From OFF to ON, low-beta power increased in the PIGD group (+1.26 dB, 95% CI [0.48, 2.04]) but showed little change in the TD group (-0.20 dB, 95% CI [-1.02, 0.63]). This interaction remained stable in influence and leave-one-out analyses. The prespecified primary wPLI endpoint was not significant (p = 0.153). In exploratory analyses, high-beta (21-35 Hz) ΔwPLI between the right cerebellar Crus I and right lobule VI differed between subtypes and survived within-band edge-wise BH-FDR correction (q = 0.028), whereas NBS identified no significant network-level component.

Tremor-dominant and PIGD showed distinct medication-state modulation of motor-cortical low-beta power, with M1 low-beta relative PSD emerging as the most consistent electrophysiological difference in this cohort. By contrast, cerebellum-related connectivity findings were limited to exploratory edge-wise effects and require independent replication.