The role of hippocampal processing and slow-wave activity in memory consolidation

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 DESCRIPTION (provided by applicant): Sleep plays a critical role in long-term memory consolidation, or the stabilization of recent memories over time. In humans, non-rapid-eye-movement (NREM) sleep, compared to time spent awake, is associated with enhanced memory retention and the stabilization of memory representations across hippocampal-cortical networks. Specific physiological mechanisms during post-encoding sleep are thought to support such memory stabilization: slow wave activity or slow oscillations, which coordinate and synchronize large-scale neural activity during NREM sleep, and the reactivation of hippocampal activity patterns representative of prior experience (`reactivation') during wide-spread hippocampal-cortical network interactions. A functional role of slow waves for the retention of recent memories has been shown in humans, and robust evidence for memory- related hippocampal reactivation and associated hippocampal network interactions has been shown during NREM sleep in rodents. However, it is unclear from prior work 1): which brain regions are critically necessary for the generation of slow waves that support successful NREM memory consolidation, with prior work indicating a predominance of slow wave density and origin over medial prefrontal cortex (mPFC), and 2): whether mechanisms of hippocampal reactivation and large-scale network interactions support human NREM memory consolidation, as little prior work has tested evidence for hippocampal reactivation and associated network interactions in the human brain. By combining TMS with high-density EEG and EEG-fMRI measurements of NREM brain activity, this proposal seeks to remedy these gaps by 1): testing the causal contribution of mPFC integrity to slow wave activity generation and associated NREM sleep memory consolidation, and by 2): testing whether hippocampal-dependent learning results in robust evidence for hippocampal reactivation and large-scale network interactions during subsequent NREM sleep, and whether NREM hippocampal activity measures are functionally predictive of memory consolidation success (memory retention and neural stabilization across hippocampal-cortical networks). In sum, this work aims to study the underlying brain regions and neural mechanisms that critically contribute to long-term memory retention during sleep in humans. This proposal will improve our understanding of basic memory mechanisms that may underlie memory deficits in psychiatric and neurological disease states, which often express co-morbid impairments in memory and sleep abnormalities. Moreover, this work will elucidate the functional significance of sleep loss associated with several neurological disorders and will aid in the successful development of therapeutics to ameliorate memory deficits by targeting modifiable aspects of sleep physiology.