The neural replay mechanisms of episodic memory consolidation under stress in humans

Abstract: Memory consolidation typically occurs slowly during rest or sleep periods following memory encoding. Under stress, though, the consolidation of memories may accelerate considerably. The mechanisms underlying this rapid memory consolidation in stressful circumstances remain unclear, primarily due to the longstanding absence of quantitative methodologies for investigating the neural activities during the human memory consolidation. This research aims to employ computational neuroscience techniques to meticulously characterize neural replay during the consolidation of episodic memory under stress. Specifically, we propose an integrated approach involving cognitive psychology, neuroimaging, machine learning, neuroendocrine regulation, stress induction, and physiological and neuroendocrine assessments to examine the ’double-edged sword’ hypothesis related to stress and neural replay. Although stress might hasten the rate of neural replay, thereby facilitating memory consolidation, it could simultaneously compromise the accuracy of neural replay and disrupt its sequentiality. Our study will: (1) juxtapose the multi-dimensional characteristics of neural replay under stress and non-stress conditions; (2) probe the interplay between neural replay and memory retrieval and encoding in stressful conditions; and (3) strive to employ neuroendocrine and environmental tactics to modulate human stress responses, which in turn could influence neural replay during consolidation. The implications of this research are twofold: it could help identify the optimal brain state to enhance memory consolidation and bridge the gap between human and animal studies on neural replay. At the same time, it could illuminate new strategies for preserving episodic memory function under stress and intervening in memory deficits seen in stress-associated psychiatric disorders.