• Julia Ladenbauer, Liliia Khakimova, Robert Malinowski, Daniela Obst, Eric Tönnies, Daria Antonenko, Klaus Obermayer, Jeff Hanna, and Agnes Flöel.
• Department of Neurology, Universitätsmedizin Greifswald, Greifswald, Germany.
• Neuromodulation. 2023 Dec 1; 26 (8): 159216011592-1601.

BackgroundOscillatory rhythms during sleep, such as slow oscillations (SOs) and spindles and, most importantly, their coupling, are thought to underlie processes of memory consolidation. External slow oscillatory transcranial direct current stimulation (so-tDCS) with a frequency of 0.75 Hz has been shown to improve this coupling and memory consolidation; however, effects varied quite markedly between individuals, studies, and species. In this study, we aimed to determine how precisely the frequency of stimulation must match the naturally occurring SO frequency in individuals to best improve SO-spindle coupling. Moreover, we systematically tested stimulation durations necessary to induce changes.Materials And MethodsWe addressed these questions by comparing so-tDCS with individualized frequency to standardized frequency of 0.75 Hz in a within-subject design with 28 older participants during napping while stimulation train durations were systematically varied between 30 seconds, 2 minutes, and 5 minutes.ResultsStimulation trains as short as 30 seconds were sufficient to modulate the coupling between SOs and spindle activity. Contrary to our expectations, so-tDCS with standardized frequency indicated stronger aftereffects regarding SO-spindle coupling than individualized frequency. Angle and variance of spindle maxima occurrence during the SO cycle were similarly modulated.ConclusionsIn sum, short stimulation trains were sufficient to induce significant changes in sleep physiology, allowing for more trains of stimulation, which provides methodological advantages and possibly even larger behavioral effects in future studies. Regarding individualized stimulation frequency, further options of optimization need to be investigated, such as closed-loop stimulation, to calibrate stimulation frequency to the SO frequency at the time of stimulation onset.Clinical Trial RegistrationThe Clinicaltrials.gov registration number for the study is NCT04714879.Copyright © 2022. Published by Elsevier Inc.

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