Interactions of sleep oscillations and synaptic scaling processes across NREM-REM sleep states in healthy and pathological aging: A combined experimental-computational approach

ⓘ Image creditImage Time frequency representation (TFR) in the frequency range of 5 to 20 Hz for SO (left) and delta (right) events. Courtesy of B03 members

Sleep is known to play an active role in long-term memory consolidation. However, interplay between NREM-REM sleep stages and recalibration of Excitatory/Inhibitory balance (E/I), their combined contribution to memory consolidation, and brain regions underlying these processes, remain poorly understood, and little is known on how pathological aging impacts on these processes. Our project will address these questions through use of sleep stage specific transcranial current stimulation protocols and computational brain modeling to causally investigate NREM-REM interactions, cortical excitability, memory and overnight homeostatic recalibration in healthy older adults, patients with Alzheimer’s Disease (AD), and epilepsy patients with intracranially implanted electrodes. In a theoretical approach, we will infer mechanisms underlying the empirically observed interplay of E/I balance with oscillations, cortical traveling waves and memory consolidation. Overall, we will be able to infer causal relationships between structural and neurobiological changes, E/I balance and altered memory consolidation performance during aging and AD.

Image Time frequency representation (TFR) in the frequency range of 5 to 20 Hz for SO (left) and delta (right) events. Courtesy of B03 members

Archive – B03 (SFB1315/1)

Archive – B03 (SFB1315/2)

ⓘ Image creditImage courtesy of B03

Graphical Abstract: WP1 Develop protocol for REM sleep modulation to modify excitatory/inhibitory (E/I) balance in healthy older volunteers (HOV); WP2 Build individual brain network models to reproduce induced E/I balance changes; WP3 Evaluate causal interdependencies by means of REM- and NREM-specific modulation including effects on memory, in HOV and epilepsy patients with intracranial electrodes (EPI); WP4 Compare to patients with Alzheimer’s Disease (AD); WP5 Construct models with REM and NREM sleep modulation reproducing EEG signatures and memory performance; Reproduce and compare data from AD patients in a multiscale mathematical model.