0438 Digital Neuromodulation Targeting Hyperarousal in Insomnia: Neurophysiological Mechanisms of Self-Regulated Auditory Biofeedback

Abstract Introduction Self-Regulated Auditory Biofeedback (SAB) represents a novel app-based digital therapeutic for insomnia that uses real-time physiological monitoring to deliver personalized acoustic stimulation targeting hyperarousal. Preliminary clinical studies have demonstrated rapid therapeutic benefits, with patients experiencing improved sleep onset and quality within days. However, the neurophysiological mechanism of action underlying these clinical improvements remains incompletely characterized. This study addresses this knowledge gap through comprehensive multimodal investigation of how closed-loop auditory neuromodulation modulates autonomic, cortical, and interoceptive systems in individuals with chronic insomnia. Methods Eighty adults with chronic insomnia were randomized to receive either SAB(pipeline code: BELL001) or sham stimulation during a single 70-minute laboratory session comprising resting baseline, conscious biofeedback, and subconscious biofeedback phases. The SAB system continuously captured cardiac, respiratory, and neural signals, dynamically optimizing acoustic parameters in real-time based on individual physiological states. Sham condition delivered non-contingent audio without closed-loop adaptation. Continuous high-density EEG, heart rate variability (HRV) metrics, respiration, and electromyography were recorded throughout. Interoceptive accuracy was assessed at baseline. Autonomic stability, cortical arousal patterns, and interoceptive moderation effects were analyzed across intervention phases. Results Compared with sham, SAB produced greater autonomic stability and reductions in cortical arousal markers. EEG analyses revealed decreased frontal high-frequency activity and increased posterior alpha power, indicating transition toward sleep-permissive states. Individuals with higher baseline interoceptive sensitivity showed substantially larger treatment responses during SAB, but not during sham stimulation. Conclusion This study provides the first comprehensive neurophysiological characterization of SAB, demonstrating that real-time auditory neuromodulation produces immediate, measurable reductions in hyperarousal through coordinated downregulation of autonomic and cortical arousal systems. The capacity to induce acute neurophysiological changes via non-invasive digital stimulation represents a paradigm shift in insomnia treatment, offering scalable, accessible intervention without pharmacological risks or therapist dependency. Interoceptive sensitivity showed an associative pattern with treatment response, warranting further investigation before being considered for biomarker-based personalization. These mechanistic insights establish the scientific foundation for app-based digital therapeutics in sleep medicine and demonstrate that neuromodulation can be rigorously validated using objective neurophysiological endpoints, advancing the field toward evidence-based precision digital medicine. Support (if any) Support: KIST, BELL Therapeutics Inc.