Abstract:

Memory consolidation typically unfolds gradually during rest or sleep following encoding. However, under stress, the consolidation process can significantly accelerate. This phenomenon has been supported by previous studies in both animals and humans, suggesting that stress can enhance memory consolidation. Yet, the mechanisms driving this accelerated consolidation under stress remain elusive, largely due to a historical lack of quantitative methods for probing neural activity during human memory consolidation phases. Contrary to the conventional perspective, our research posits that stress doesn't simply boost or hinder consolidation. Indeed, while stress increases the pace of neural replay, it also introduces memory distortions and diminishes sequential integrity. Our aim is to leverage computational neuroscience techniques to precisely delineate neural replay dynamics during episodic memory consolidation under stress. We advocate an integrated methodology that combines cognitive psychology, neuroimaging, machine learning, neuroendocrine studies, stress induction, and both physiological and neuroendocrine evaluations to investigate the nuanced impacts of stress on memory consolidation and neural replay, embodying the 'double-edged sword' hypothesis: despite stress potentially accelerating neural replay and facilitating consolidation, it may also impair replay accuracy and disrupt sequence.

Our experimental design is meticulously crafted to dissect the multifaceted influence of stress on memory consolidation. The development of a new neural replay index based on rapid EEG/MEG signals aims to assess replay speed, accuracy, and sequentiality in unprecedented detail. This index is a cornerstone of our methodology, enabling the quantification of neural replay's temporal dynamics, fidelity, and order. To complement this, we will apply diverse memory retrieval paradigms to evaluate the functional outcomes of consolidation under stress. These include a durability test, assessing participants' ability to maintain memory traces over extended periods; a specificity test, examining the recall of precise episodic details versus generalized or incorrect information; and a flexibility test, determining the capacity to apply remembered information to novel problem-solving scenarios.

Furthermore, our study will conduct in-depth brain-behavior correlation analyses to link the neural replay index with specific memory outcomes. We hypothesize that rapid neural replay correlates with enduring memories, while compromised replay precision and sequence relate to diminished memory specificity and adaptability. This nuanced exploration will allow us to juxtapose neural replay characteristics under stress versus non-stress conditions and examine the intricate relationship between neural replay and memory processes during stress.

To rigorously test whether retrieval practice before stress exposure can mitigate its negative effects on consolidation, we will implement a pre-stress retrieval practice session in a subset of participants. This approach will enable us to evaluate the protective effects of active recall against stress-induced memory distortion. Additionally, we aim to utilize neuroendocrine and environmental strategies to modulate stress responses, potentially influencing neural replay during consolidation. Specifically, we will explore the efficacy of cortisol blockers to mitigate stress effects and environmental interventions designed to enhance cognitive resilience against stress.

We anticipate that our findings will unveil stress-induced interactions among memory, emotion, and control networks, primarily involving the amygdala, hippocampus, and prefrontal cortex. Neuroendocrine interventions could directly reduce amygdala activity, enhancing prefrontal-hippocampal connectivity, whereas environmental strategies might bolster prefrontal control over the amygdala, thus promoting a neurobiological environment conducive to optimal memory consolidation.

The implications of our research are profound and far-reaching. By identifying conditions that enhance memory consolidation, we aim to bridge significant gaps between human and animal studies on neural replay. Moreover, our findings could illuminate new strategies for maintaining episodic memory function under stress and offer novel intervention approaches for memory deficits observed in stress-associated psychiatric disorders. Ultimately, this research could pave the way for groundbreaking treatments that harness the neuroplasticity of memory systems, offering hope to individuals suffering from memory impairments and contributing to the broader scientific understanding of memory under stress.

Key words: memory consolidation, memory retrieval, acute stress, neural replay, episodic memory