Fixed-Sequence OFF-to-ON Differences in Low-Beta State Dynamics in Parkinson's Disease: A Paired Source-Space...

Resting-state EEG studies in Parkinson's disease (PD) have largely emphasized static power or connectivity, whereas fixed-sequence OFF-to-ON session differences may also involve the temporal organization of network states. Paired source-space evidence under such fixed acquisition protocols remains limited. We analyzed 64-channel eyes-closed resting-state EEG in 39 patients with PD contributing paired OFF/ON recordings for the prespecified 90 s primary analysis; 24 also contributed paired 178 s recordings for duration robustness. After individual MRI-based source reconstruction, low-beta (13-20 Hz) dynamic amplitude-envelope connectivity was computed with 2 s windows. Primary endpoints were switching rate (SR) and normalized Shannon entropy (H); fractional occupancy (FO_path) and mean dwell time (MDT_path) of an internally defined OFF-dominant state were prespecified secondary conditional endpoints and are interpreted only as conditional summaries. PD-only linear mixed-effects models quantified the fixed-sequence OFF-to-ON session contrast; medication state and session order were necessarily collinear. In the 90 s analysis, the later ON session showed higher SR (β = 3.3224, Holm p = 0.00406) and H (β = 0.06781, Holm p = 0.000749) than the earlier OFF session. FO_path (β = -0.09167, Holm p = 1.08 × 10⁻⁵) and MDT_path (β = -1.05171, Holm p = 0.00524) were lower in the later ON session. The 178 s reanalysis preserved the same directions, although SR and especially MDT_path were more parameter-sensitive across sensitivity analyses. The fixed OFF-then-ON protocol was associated with reproducible within-subject differences in low-beta state dynamics, with the strongest evidence arising from SR and H. Because medication state was perfectly collinear with session order, these findings cannot distinguish medication-specific effects from order-, time-, vigilance-, fatigue-, or adaptation-related influences. FO_path and MDT_path remain conditional summaries tied to an internally defined OFF-dominant state, and MDT was less stable in the 178 s and OFF-only sensitivity analyses.