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bioRxiv · 10.64898/2025.12.19.695567

Closed-loop acoustic stimulation modified by cathodal tDCS is beneficial for retention

Hoefer, T.·Hoesel, T.·Hansen, K.·Moelle, M.·Peifer, C.·Bazhenov, M.·Marshall, L.
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Abstract

We investigated how combining transcranial direct current stimulation (tDCS) with closed-loop acoustic stimulation (CLAS) during slow-wave sleep (SWS) affects memory consolidation and sleep-related neural oscillations. Cathodal tDCS was used to slightly reduce cortical excitability, thereby simulating a shifted brain state during CLAS and allowing us to compare the effects of standard CLAS to CLAS delivered under altered cortical conditions (CmodCLAS). Twenty-three participants (mean age 21.3 {+/-} 2.6 years) completed two experimental nights: one with CLAS alone and one with CLAS combined with cathodal tDCS (CmodCLAS). Overnight retention on declarative memory tasks and morning learning performance were assessed. Memory outcomes revealed that CmodCLAS, but not CLAS alone, significantly improved overnight retention on the figural paired-associate task. In the EEG, CmodCLAS shifted the time-locked response to acoustic stimulation toward more negative potential values at the frontal region. CmodCLAS also prolonged slow oscillation (SO) duration at frontal sites while shortening SO duration at occipital sites, an effect not observed during standard CLAS. These findings demonstrate that the baseline level of cortical excitability during sleep modulates both the cognitive and electrophysiological effects of CLAS. They highlight the importance of brain state for non-invasive CLAS during sleep and suggest that CmodCLAS may serve as a useful approach for enhancing prefrontal cortical function during SWS. Significance statementNon-invasive brain stimulation (NIBS) is a promising approach to modulate brain activity and function. Unfortunately, NIBS studies are challenged by heterogenous findings. In addition to protocol differences, variability may depend strongly on the brains baseline activity (or brain state). Here, we used transcranial direct current stimulation (tDCS) to simulate a different brain state while applying closed-loop acoustic stimulation (CLAS) during slow-wave sleep (SWS). Sleep has been shown to enhance overnight memory retention. Results demonstrated significantly improved retention performance for cathodal tDCS modulated CLAS (CmodCLAS) as compared to CLAS alone. Furthermore, electrophysiological responses time-locked to the acoustic stimulus and spontaneous electrophysiological rhythms of SWS suggest that hippocampo-cortical function was specifically enhanced by CmodCLAS. Thus, underscoring the potential therapeutic relevance of CmodCLAS.

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Hoefer, T., Hoesel, T., Hansen, K., Moelle, M., Peifer, C., Bazhenov, M., Marshall, L.. 2025-12-23. Closed-loop acoustic stimulation modified by cathodal tDCS is beneficial for retention. https://doi.org/10.64898/2025.12.19.695567

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