Study Objectives Synchronization of neural activity within local networks and between brain regions is a major contributor to rhythmic field potentials such as the EEG. On the other hand, dynamic changes in microstructure and activity are reflected in the EEG, for instance slow oscillation (SO) slope can reflect synaptic strength. SO-spindle coupling is a measure for neural communication. It was previously associated with memory consolidation, but also shown to reveal strong inter-individual differences. In studies, weak electric current stimulation has modulated brain rhythms and memory retention. Here we investigate whether SO-spindle coupling and SO slope during baseline sleep are associated with (predictive of) stimulation efficacy on retention performance. Methods Twenty-five healthy subjects participated in three experimental sessions. Sleep-associated memory consolidation was measured in two sessions, in one anodal transcranial direct current stimulation oscillating at subjects individual SO frequency (so-tDCS) was applied during nocturnal sleep. The third session was without a learning task (baseline sleep). The dependence on SO-spindle coupling and SO-slope during baseline sleep of so-tDCS efficacy on retention performance were investigated. Results Stimulation efficacy on overnight retention of declarative memories was associated with nesting of slow spindles to SO trough in deep non-rapid eye movement baseline sleep. Steepness and direction of SO slope in baseline sleep were features indicative for stimulation efficacy. Conclusions Findings underscore a functional relevance of activity during the SO up-to-down state transition for memory consolidation and provide support for distinct consolidation mechanisms for types of declarative memories.

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Slow oscillatory- (so-) tDCS has been applied in many sleep studies aimed to modulate brain rhythms of slow wave sleep and memory consolidation. Yet, so-tDCS may also modify coupled oscillatory networks. Efficacy of weak electric brain stimulation is however variable and dependent upon the brain state at the time of stimulation (subject and/or task-related) as well as on stimulation parameters (e.g., electrode placement and applied current. Anodal so-tDCS was applied during wakefulness with eyes-closed to examine efficacy when deviating from the dominant brain rhythm. Additionally, montages of different electrodes size and applied current strength were used. During a period of quiet wakefulness bilateral frontolateral stimulation (F3, F4; return electrodes at ipsilateral mastoids) was applied to two groups: ‘Group small’ (n = 16, f:8; small electrodes: 0.50 cm2; maximal current per electrode pair: 0.26 mA) and ‘Group Large’ (n = 16, f:8; 35 cm2; 0.35 mA). Anodal so-tDCS (0.75 Hz) was applied in five blocks of 5 min epochs with 1 min stimulation-free epochs between the blocks. A finger sequence tapping task (FSTT) was used to induce comparable cortical activity across sessions and subject groups. So-tDCS resulted in a suppression of alpha power over the parietal cortex. Interestingly, in Group Small alpha suppression occurred over the standard band (8–12 Hz), whereas for Group Large power of individual alpha frequency was suppressed. Group Small also revealed a decrease in FSTT performance at retest after stimulation. It is essential to include concordant measures of behavioral and brain activity to help understand variability and poor reproducibility in oscillatory-tDCS studies.

Sleep is able to contribute not only to memory consolidation, but also to post-sleep learning. The notion exists that either synaptic downscaling or another process during sleep increase post-sleep learning capacity. A correlation between augmentation of the sleep slow oscillation and hippocampal activation at encoding support the contribution of sleep to encoding of declarative memories. In the present study, the effect of closed-loop acoustic stimulation during an afternoon nap on post-sleep encoding of two verbal (word pairs, verbal learning and memory test) and non-verbal (figural pairs) tasks and on electroencephalogram during sleep and learning were investigated in young healthy adults (N = 16). Closed-loop acoustic stimulation enhanced slow oscillatory and spindle activity, but did not affect encoding at the group level. Subgroup analyses and comparisons with similar studies lead us to the tentative conclusion that further parameters such as time of day and subjects' cognitive ability influenced responses to closed-loop acoustic stimulation.