Closed-loop Auditory Stimulation during Sleep Improves Procedural Memory Consolidation

Bryan S. Baxter, PhD

Massachusetts General Hospital
Closed-loop Auditory Stimulation during Sleep Improves Procedural Memory Consolidation

Scientific Abstract

BACKGROUND: Sleep-dependent memory consolidation relies on the temporal coordination of sleep oscillations, including cortical slow oscillations (SOs) and thalamic spindles, during non-rapid-eye- movement (NREM) sleep. In schizophrenia reduced sleep spindles correlate with impaired sleep- dependent memory consolidation. Yet treatments that improve memory impairments are lacking.

Auditory stimulation, time-locked to the SO upstate, is a promising potential treatment. In healthy adults it evokes SOs and spindles, and improves declarative memory. We investigated whether auditory stimulation evokes coupled SO-spindle events and improves procedural memory.

METHODS: 20 healthy adults participated in two afternoon nap sessions (pink noise stimulation during the SO upstate and no stimulation) with polysomnography. Participants trained on the finger tapping Motor Sequence Task at the start of each session and were tested after the nap. The improvement in correct trials from the end of training to the start of testing indexes sleep-dependent memory consolidation. SOs and spindles were detected during NREM sleep using validated automated detectors.

RESULTS: Auditory stimulation significantly improved memory consolidation (z=1.8, p=.03) compared to no stimulation. The higher the stimulation rate (#/min), the greater the memory improvement in the stimulation (r=.52 , p<.05), but not no stimulation (r=.32, p=.16 ) condition, although these relations did not differ significantly. Stimulation evoked coupled SO-spindle events in a fronto-central cluster of electrodes (t-stat=49.6, p<.02). Coupled SO-spindle density (#/min) in a centro-parietal cluster significantly correlated with memory improvement (R2=.34, p<.01).

CONCLUSIONS: Closed-loop auditory stimulation improves procedural memory consolidation. The higher the rate of stimulation, the greater memory consolidation, suggesting a dose-dependent effect.

Stimulation also evokes coordinated spindle-SO events that mediate this consolidation. This motivates the investigation of auditory stimulation as a non-invasive and potentially scalable treatment for sleep- dependent memory deficits in patients with schizophrenia.

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Bryan S. Baxter, PhD, Dimitris Mylonas, PhD, Kristi S. Kwok, BS, Christine E. Talbot, MS, Rudra Patel, BS, Lin Zhu, PhD, Robert Stickgold, PhD, Dara S. Manoach, PhD

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