Altered heart-brain coupling in awake patients with isolated REM sleep behaviour disorder

Isolated REM Sleep Behaviour Disorder (iRBD) represents an early stage of α-synucleinopathy, often preceding Parkinson’s disease, dementia with Lewy bodies or Multiple System Atrophy. Growing evidence shows that iRBD patients are not only characterized by sleep disturbances but also dysautonomia. However, whether the brain–body coupling reflecting the interaction between neural and peripheral physiological activity is altered in iRBD remains unknown. Leveraging whole-night polysomnography data from thirty-six participants, we quantified heart–brain coupling via heartbeat evoked potentials (HEPs) across wakefulness, NREM, and REM sleep. HEPs were compared between individuals with isolated REM sleep behavior disorder (iRBD; n = 13) and healthy controls (HC; n = 23). In addition, heart rate variability (HRV) and other ECG-derived features were analyzed. During wakefulness, iRBD patients showed altered HEP compared to HC, between 230 and 445 ms after the R-peak. over frontal regions. The duration of RBD symptoms was positively associated with the magnitude of these HEP alterations. HEP alterations were specific to wakefulness, as no differences were observed during NREM or REM sleep. Additional analyses showed that HEP alterations in iRBD during wakefulness were not driven by ECG differences. We corroborate previous findings of altered heart rate variability (HRV) in iRBD patients during REM sleep. We demonstrate that brain-body coupling, as indexed by HEP, is altered during wakefulness in iRBD patients. These diurnal HEP may represent a novel quantitative biomarker of iRBD, and could, in the future, serve as a marker for the phenoconversion to α-synucleinopathy.