Polarity-dependent modulation of sleep oscillations and cortical excitability in aging

• Published in: bioRxiv
• Main Authors: Dikici, Buse, Malinowski, Robert, Kordass, Jan-Bernhard, Obermayer, Klaus, Ladenbauer, Julia, Floeel, Agnes
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Laboratory 2025; 04.07.2025
• Edition: 1.1
• Subjects: Neuroscience
• ISSN: 2692-8205
• DOI: 10.1101/2025.07.03.662520

During non-rapid eye movement (NREM) sleep, cortical slow oscillation (SO; <1 Hz) activity and thalamic sleep spindles (12-15 Hz) interact through precise phase coupling to support memory consolidation. Slow oscillatory transcranial direct current stimulation (so-tDCS) can modulate these oscillations. Traditionally, anodal so-tDCS is used to depolarize the cortex during SO up-states, thereby promoting SO activity and SO-spindle coupling. However, intracranial findings suggest that SO down-states, characterized by cortical hyperpolarization, can trigger thalamic spindle bursts. This raises the hypothesis that cathodal so-tDCS, by promoting hyperpolarization, could selectively enhance down-states and more effectively improve SO-spindle coupling. We tested this hypothesis in twenty-two healthy older adults, a population known to exhibit diminished NREM oscillatory activity. Each participant received cathodal, anodal, and sham so-tDCS in separate nap sleep sessions. We quantified SO and spindle characteristics, their temporal coupling, and cortical excitation/inhibition (E/I) balance using EEG spectral slope. We also assessed individual circadian preference (chronotype) as a potential moderator. We found that anodal so-tDCS improved SO-spindle synchrony, and increased spindle power over sham in participants with intermediate or evening chronotypes, while cathodal so-tDCS did not enhance these oscillatory measures compared to sham, despite prolonging SO down-states. Anodal stimulation also elevated E/I balance, indicating increased cortical excitability, while cathodal stimulation did not produce the anticipated opposite shift. In summary, anodal, but not cathodal so-tDCS, effectively enhanced thalamocortical interactions underlying memory consolidation. Furthermore, these findings highlight the importance of individual factors such as chronotype in brain stimulation responsiveness.