0113 Evaluating Closed-Loop Auditory Stimulation During Sleep as an Intervention to Improve Memory Consolidation Deficits in Schizophrenia

Abstract

Introduction Converging evidence supports the hypothesis that reduced sleep spindles and spindle-slow oscillation (SO) coordination contribute to cognitive deficits in schizophrenia. Closed-loop auditory stimulation in healthy adults increases sleep spindles and improves declarative memory consolidation. Here we investigated whether closed-loop auditory stimulation also improves sleep-dependent procedural memory consolidation as a first step towards an intervention in schizophrenia. Methods Thirteen healthy adults participated in two nap sessions (stimulation or detection only) with polysomnography in a counterbalanced order. Participants were trained on the finger tapping Motor Sequence Task (MST), which measures sleep-dependent motor procedural memory consolidation, prior to napping and were tested after awakening. We detected the negative peak of SOs during non-REM sleep and, in the stimulation condition, delivered 50ms of pink noise during the SO up-state. Results Auditory stimulation increased SOs and spindles during the SO up-state in a frontocentral cluster of electrodes 800-1200ms after stimulation compared to detection only (p<0.05). Stimulation also showed promise for improving memory consolidation (33% increase in MST overnap improvement from detection-only) but this did not reach significance in this small sample and data collection is ongoing. Conclusion Auditory stimulation evoked coordinated spindle-SO events that mediate memory consolidation, but more subjects are needed to evaluate whether it also improves memory. If it does, we will test the effects of stimulation on sleep-dependent memory deficits in patients with schizophrenia. Closed-loop auditory stimulation shows promise as a safe, scalable intervention for cognitive deficits that can be implemented at home with commercially available devices. Support R01 MH67720 (DSM & RS), NIH-NHLBI 5T32HL007901-17 (BB), K24MH099421 (DSM), and Simons Foundation (DSM).

Neurophysiological Correlates of Phase-Specific Enhancement of Motor Memory Consolidation via Slow-Wave Closed-Loop Targeted Memory Reactivation

“…Accordingly, prior research has used experimental interventions to target plasticity processes during this window and, in turn, influence memory consolidation during sleep. In line with our findings, this earlier research has collectively shown that stimulating SO at the up-phase of the slow-oscillation enhanced the amplitude of ongoing SOs 17–21,25–27,29,33 , sigma oscillation power during the ascending phase of the SO 18–20 and memory consolidation 17–21,26,27 . Interestingly, the time-locking of the sigma burst to the up-phase of the SO has been shown to predict a positive outcome of consolidation 14,34 .…”

“…These phase-specific effects are in line with previous studies in which acoustic stimulations delivered in a closed-loop fashion at the up-phase (or during the down-to-up transition) of the SO have been shown to enhance declarative memory consolidation 17,20,21,25–27 (but see 26,28 for null effects). We are only aware of one study using closed-loop acoustic stimulation in the motor memory domain and results showed no benefit of SO up-stimulation on motor performance 29 . The discrepancy between this recent research and our findings is unclear but we speculate that methodological differences between studies, such as time afforded in NREM sleep (nap vs. night paradigm) or stimulation phase (380ms post-trough vs. peak), might have contributed to these inconsistencies.…”

Neural reactivation during human sleep

“…Correlational studies have reported that the memory benefits of sleep are best when spindles consistently couple to the peaks of SOs (33)(34)(35)(36)(37)(38)(39). Furthermore, these SO-coupled spindles are significantly better predictors of memory than uncoupled spindles (40)(41)(42)(43), highlighting the importance of oscillatory coupling in memory consolidation. Moving beyond correlational evidence, electrical and acoustic stimulation has been used to enhance SO-spindle coupling (44,45), leading to improvements in memory (46,47).…”