NSF/SBE-BSF: The role of sleep in memory consolidation: intracranial human electrophysiology and electrical stimulation

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Memory loss is one of the most devastating afflictions of the human condition. Sleep is important for learning and memory because it improves memory consolidation - the transformation of new memories that are formed during wakefulness into stable memories that are integrated into pre-existing long-term memories. This is particularly true for memory for facts and events (declarative memory), which depends on brain regions in and around the human hippocampus. There is evidence that declarative hippocampus-dependent memories are consolidated during a sleep-stage called slow-wave-sleep, where large slow waves dominate brain activity. This consolidation is thought to be mediated by interactions between the hippocampus and brain areas in the frontal cortex. In this project, the researchers aim to study the effects of sleep on learning and memory in epilepsy patients implanted with depth electrodes for clinical monitoring. This setting provides a rare opportunity for direct recordings from inside the human brain, including at the level of individual neurons. The project also affords a unique opportunity to stimulate the brain during sleep, which is necessary for establishing a causal relationship between sleep and consolidation. This research will advance scientific knowledge on how specific sleep processes aid memory consolidation, and benefit society by training students in this integrative field, and developing new methods. The results may have implications for individuals suffering from neurological disorders affecting memory. Results will be disseminated broadly through participation in conferences and workshops, as well as media channels and the internet. The proposed research studies the causal role that sleep plays in memory consolidation, and is based on a an opportunity to record and stimulate neuronal activity directly from the human brain down to the level of single neurons. Upon informed consent, epilepsy patients at UCLA implanted with intracranial depth electrodes will participate in learning/memory paradigms combined with recordings and intracranial electrical stimulation during sleep. The researchers intend to advance beyond the state-of-the-art by having participants perform a learning task before sleep, record and manipulate brain activity during sleep, and evaluate subsequent memory after sleep. First, they will validate the behavioral benefits of sleep on memory consolidation. This study will be performed at UCLA with epilepsy patients (PI: Itzhak Fried), and in parallel in collaboration with Dr. Yuval Nir's lab in Israel (with healthy volunteers). The study will develop and validate paradigms that are reliable and sensitive to the beneficial effects of sleep, and short naps in particular, on declarative memory among individuals with variable memory performance. The study focuses on a learning task involving object-position associations, as well as paired associations between object and person images. Second, the research team will determine which sleep activities correlate best with learning and memory improvements as compared to no-sleep conditions. Finally, the team will evaluate causal mechanisms through intracranial stimulation to determine whether stimulation locked to endogenous slow oscillations promotes memory consolidation. A key prediction is that sleep in conjunction with such real-time closed-loop stimulation will benefit memory performance to a greater extent than undisturbed sleep.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.