Dynamic heart rate variability assessment based on fixed-frequency auditory perturbation in prolonged disorders of consciousness

Accurate differentiation between unresponsive wakefulness syndrome/vegetative state (UWS/VS) and minimally conscious state or emergence from the minimally conscious state (MCS/EMCS) remains clinically challenging in prolonged disorders of consciousness (pDoC), particularly when behavioral responses fluctuate or motor output is limited. We investigated whether short-term heart rate variability (HRV) responses to a standardized 40-Hz auditory perturbation could provide complementary bedside physiological information. Fifty-five patients with pDoC underwent a 10-minute protocol consisting of a 5-minute resting baseline followed by 5 minutes of binaural 40-Hz amplitude-modulated auditory stimulation, with continuous ECG recording. Resting HRV features showed no clear group-level separation between UWS/VS and MCS/EMCS, whereas stimulus-evoked time-domain changes, particularly \(Δ\) NN50 and \(Δ\) pNN50, differed between groups after false-discovery-rate correction. Exploratory logistic regression models based on NN50- and pNN50-related response features showed measurable internal held-out test performance. These findings suggest that standardized auditory-evoked HRV dynamics may provide a low-burden physiological complement to repeated Coma Recovery Scale-Revised assessment. The results remain exploratory and require validation in larger independent cohorts.