Facilitatory/inhibitory intracortical imbalance in REM sleep behavior disorder: early electrophysiological marker of neurodegeneration?

Study Objectives: Previous studies found an early impairment of the short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) to transcranial magnetic stimulation (TMS) in Parkinson's disease. However, very little is known on the TMS correlates of rapid eye movement (REM) sleep behavior disorder (RBD), which can precede the onset of a a-synucleinopathy. Methods: The following TMS measures were obtained from 14 de novo patients with isolated RBD and 14 age-matched healthy controls: resting motor threshold, cortical silent period, latency and amplitude of the motor evoked potentials, SICI, and ICF. A cognitive screening and a quantification of subjective sleepiness (Epworth Sleepiness Scale [ESS]) and depressive symptoms were also performed. Results: Neurological examination, global cognitive functioning, and mood status were normal in all participants. ESS score was higher in patients, although not suggestive of diurnal sleepiness. Compared to controls, patients exhibited a significant decrease of ICF (median 0.8, range 0.5-1.4 vs. 1.9, range 1.4-2.3; p < 0.01) and a clear trend, though not significant, towards a reduction of SICI (median 0.55, range 0.1-1.4 vs. 0.25, range 0.1-0.3), with a large effect size (Cohen's d: -0.848). REM Sleep Atonia Index significantly correlated with SICI. Conclusions: In still asymptomatic patients for a parkinsonian syndrome or neurodegenerative disorder, changes of ICF and, to a lesser extent, SICI (which are largely mediated by glutamatergic and GABAergic transmission, respectively) might precede the onset of a future neurodegeneration. SICI was correlated with the muscle tone alteration, possibly supporting the proposed RBD model of retrograde influence on the cortex from the brainstem.