Driving sleep slow oscillations by auditory closed-loop stimulation-a self-limiting process.
The <1 Hz EEG slow oscillation (SO) is a hallmark of slow-wave sleep (SWS) and is critically involved in sleep-associated memory formation. Previous studies showed that SOs and associated memory function can be effectively enhanced by closed-loop auditory stimulation, when clicks are presented in synchrony with upcoming SO up states. However, increasing SOs and synchronized excitability also bear the risk of emerging seizure activity, suggesting the presence of mechanisms in the healthy brain that counter developing hypersynchronicity during SOs. Here, we aimed to test the limits of driving SOs through closed-loop auditory stimulation in healthy humans. Study I tested a "Driving stimulation" protocol (vs "Sham") in which trains of clicks were presented in synchrony with SO up states basically as long as an ongoing SO train was identified on-line. Study II compared Driving stimulation with a "2-Click" protocol where the maximum of stimuli delivered in a train was limited to two clicks. Stimulation was applied during SWS in the first 210 min of nocturnal sleep. Before and after sleep declarative word-pair memories were tested. Compared with the Sham control, Driving stimulation prolonged SO trains and enhanced SO amplitudes, phase-locked spindle activity, and overnight retention of word pairs (all ps < 0.05). Importantly, effects of Driving stimulation did not exceed those of 2-Click stimulation (p > 0.180), indicating the presence of a mechanism preventing the development of hypersynchronicity during SO activity. Assessment of temporal dynamics revealed a rapidly fading phase-locked spindle activity during repetitive click stimulation, suggesting that spindle refractoriness contributes to this protective mechanism.
Institute for Medical Psychology and Behavioral Neurobiology, University of Tuebingen, 72076 Tuebingen, Germany, Institute for Neuro- and Bioinformatics and Graduate School for Computing in Medicine and Life Science, University of Luebeck, 23562 Luebeck, Germany.
Hong-Viet V
HV
Ngo
Institute for Medical Psychology and Behavioral Neurobiology, University of Tuebingen, 72076 Tuebingen, Germany, SILS-CNS, University of Amsterdam, 1012 WX Amsterdam, The Netherlands.
Arjan
A
Miedema
Institute for Medical Psychology and Behavioral Neurobiology, University of Tuebingen, 72076 Tuebingen, Germany.
Isabel
I
Faude
Institute for Neuro- and Bioinformatics and.
Thomas
T
Martinetz
Institute for Medical Psychology and Behavioral Neurobiology, University of Tuebingen, 72076 Tuebingen, Germany, Center of Brain, Behavior and Metabolism, University of Luebeck, 23562 Luebeck, Germany, and.
Matthias
M
Mölle
Institute for Medical Psychology and Behavioral Neurobiology, University of Tuebingen, 72076 Tuebingen, Germany, Center for Integrative Neuroscience, University of Tuebingen, 72076 Tuebingen, Germany jan.born@uni-tuebingen.de.
Jan
J
Born
D000161:Acoustic Stimulation; D000328:Adult; D000704:Analysis of Variance; D001245:Association Learning / Q000502:physiology; D001921:Brain / Q000502:physiology*; D018592:Cross-Over Studies; D004569:Electroencephalography; D005072:Evoked Potentials, Auditory / Q000502:physiology*; D005260:Female; D005583:Fourier Analysis; D006801:Humans; D008297:Male; D008568:Memory / Q000502:physiology; D010507:Periodicity; D017286:Polysomnography; D012894:Sleep Stages / Q000502:physiology*; D055815:Young Adult
auditory stimulation; closed-loop control; declarative memory consolidation; fast spindles; sleep; slow oscillations