REM sleep microstructure alterations in REM sleep behavior disorder: beyond muscle tone

Isolated rapid eye movement sleep behavior disorder is characterized by dream enactment behaviors and loss of atonia during rapid eye movement sleep. It is considered a prodromal stage of alpha-synucleinopathies and may result from dysfunction of brainstem structures regulating muscle tone in rapid eye movement sleep. Whether other rapid eye movement sleep features are affected remains unclear. Here, we investigated alterations in rapid eye movement sleep microstructure, including phasic rapid eye movement sleep, sawtooth waves, and non-rapid eye movement/rapid eye movement transitions, in isolated rapid eye movement sleep behavior disorder and rapid eye movement sleep behavior disorder associated with Parkinson's disease (Parkinson's disease + rapid eye movement sleep behavior disorder).

We retrospectively included 20 patients with isolated rapid eye movement sleep behavior disorder (85 per cent male, 66.5 [63-68] years), 20 patients with Parkinson's disease + rapid eye movement sleep behavior disorder (75 per cent male, 62.5 [57.5-65] years) and 20 controls (75 per cent male, 67 [61-70] years). Rapid eye movement sleep without atonia, bursts of rapid eye movements and sawtooth waves bursts were manually scored. Phasic rapid eye movement sleep proportion (derived from rapid eye movements), sawtooth waves density/duration/frequency, and the duration of non-rapid eye movement/rapid eye movement transitions were compared between groups with a general linear mixed-effects model.

Phasic rapid eye movement sleep proportion was higher in the isolated rapid eye movement sleep behavior disorder group (26.5 [21-33] per cent) than in the control (16.4 [12.5-22.3] per cent, p-corrected = .005) and Parkinson's disease + rapid eye movement sleep behavior disorder (17.6 [13.9-21.7] per cent, p-corrected = .005) ones. Non-rapid eye movement/ rapid eye movement transitions showed a duration gradient, increasing from controls (119.0 [58.5-186.1] s) to isolated rapid eye movement sleep behavior disorder (212.1 [68.5-391.4] s, p-corrected = .0038) and Parkinson's disease + rapid eye movement sleep behavior disorder (375.8 [217.6-514.6] s, p-corrected < .001) patients. Sawtooth waves density and duration were reduced in the Parkinson's disease + rapid eye movement sleep behavior disorder group (1.33 [1.1-1.54]/min; 2.13 [1.70-2.69] s) vs. controls (1.74 [1.52-2.05]/min, p-corrected = .005; 2.98 [2.18-4.11], p-corrected < .001), whereas altered sawtooth waves spectral content was observed in both patient's groups with a power shift toward higher frequencies (both p < .001 vs. controls).

These results reinforce the hypothesis that rapid eye movement sleep dysregulation in rapid eye movement sleep behavior disorder extends to rapid eye movement-specific electrophysiological features beyond loss of atonia and dream enactments. Statement of Significance This study compared rapid eye movement (REM) sleep microstructure between patients with isolated REM sleep behavior disorder (iRBD) or RBD associated with Parkinson's disease (PD + RBD), and controls. We found some altered REM sleep features in the patient groups vs. controls, as increased phasic REM sleep proportion in iRBD and reduced sawtooth waves (STW) density and duration in PD + RBD. Both groups exhibited altered STW spectral characteristics with a shift toward higher frequencies. Additionally, we observed a gradient in the duration of non-rapid eye movement/REM sleep transitions, increasing from controls to patients with iRBD and peaking in patients with PD + RBD, who exhibited the longest transitions. These findings highlight that REM sleep anomalies in RBD extend beyond atonia loss and dream enactments, encompassing broader microstructural changes.