Auditory Enhancement of Sleep Slow Waves in People with Parkinson Disease: A Proof-of-Concept Study

Deep sleep supports several restorative functions and has emerged as a potential therapeutic target in neurodegenerative disorders, such as Parkinsons disease (PD). Phase-targeted auditory stimulation (PTAS) is a non-invasive method for enhancing slow waves of deep sleep, measurable by increased slow-wave activity (SWA; spectral power 0.75-4.5 Hz). Here, we report the first study investigating whether PTAS can be successfully applied in PD patients with subjective sleep disturbance. We conducted a randomized, double-blind, sham-controlled, cross-over, within-subject study assessing the effects of PTAS over three nights with wearable devices at participants homes. PTAS was applied in ON and OFF windows for the entire night in 14 participants and first part of the night in nine. PTAS increased low-frequency SWA by almost 30% during ON windows in 21 analyzed participants. The SWA increased further with higher numbers of stimuli, suggesting a dose- dependent effect. Participants receiving part-night PTAS reported improved subjective daytime sleepiness after the third night. This proof-of-concept study demonstrates successful auditory enhancement of slow waves with PTAS in PD. Our observation of the potential advantages of part-night PTAS warrant further exploration. Our data encourage longer and larger trials to fully explore the potential of PTAS in PD and other neurodegenerative diseases.