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Brain computer interface to study and manipulate mamories of aversive experience during sleep

Periodic Reporting for period 4 - MNEMOSYNE (Brain computer interface to study and manipulate mamories of aversive experience during sleep)

Berichtszeitraum: 2022-04-01 bis 2023-09-30

Many of us have favorite places we frequently return to, drawn either by the quality of food or fond memories of times spent with friends. Conversely, there are certain streets we instinctively avoid on our way home, often without clear recollection of the reasons. The Mnemosyne project is focused on exploring the link between our internal spatial representation – the neural encoding of our physical surroundings – and the emotional significance we attach to these places, which encompasses both the physiological responses and the mental representation of these emotions. This exploration is structured around three primary aims.

First Aim: Studying Bodily Impact in Aversive Situations
The project's initial goal is to investigate how physiological responses, particularly those of the body, influence decision-making and memory in adverse contexts. This line of inquiry is crucial as it parallels many therapeutic approaches in humans, such as the use of meditation and breathing techniques to alleviate anxiety and mood disorders. By understanding the bodily mechanisms in these situations, we can enhance the effectiveness of such therapies.

Second Aim: Deciphering Rumination in Rodents
Our second objective is to ascertain if rumination, a persistent issue in PTSD and resistant to many pharmacological treatments, can be effectively modeled in rodents. Developing an animal model specific to this symptom could revolutionize the treatment of rumination in humans, offering new pathways for intervention and understanding.

Third Aim: Reversing Aversive Memory During Sleep
Building on initial findings that positive spatial associations can be induced during sleep, we aim to explore if adverse memories can be similarly altered. Using a brain-computer interface, we intend to investigate whether aversive experiences reactivated during sleep can have their negative valence reversed if we apply a rewarding stimulation during these sleep reactivations. This approach could offer a novel method for treating PTSD or phobic disorders, circumventing the need for patients to consciously recall traumatic events during therapies like exposure therapy or counterconditioning.

Overall Objectives and Societal Impact:
The Mnemosyne project aims to advance our understanding of how internal representations of space and emotions are encoded in the brain and how these processes can be influenced, especially in the context of mental health disorders. The outcomes of this research have the potential to significantly impact society by improving therapies for conditions like anxiety, mood disorders, and PTSD, ultimately enhancing the quality of life for individuals suffering from these conditions.

Main results and conclusion of the action:
In summary, the Mnemosyne Project enhances our knowledge of how the brain processes space and emotion and suggests new mental health therapies. Our findings also guide the development of effective exposure therapy models for traumatic disorders.
The Mnemosyne project has made several key discoveries in its investigations into fear responses and memory processing. It revealed that breathing actively modulates brain activity during fear responses, not just as a consequence, suggesting breathing-based interventions for anxiety and panic disorders. A major finding was identifying two distinct freezing behaviors in response to threats, each with unique physiological and neural patterns, challenging the conventional view of freezing as a uniform response. The project also differentiated the roles of sleep and awake Sharp-wave ripples (SWRs) in spatial aversive tasks with different actions on the spatial and the affective component of the aversive learning task. Finally, the exploration of counterconditioning highlighted its limitations, affecting only spatial avoidance in aversive learning, pointing to the need for refining exposure therapy for anxiety disorders.
The Mnemosyne project's remarkable results in neuroscience have been widely disseminated and exploited, leading to three significant academic publications with several more manuscripts in the final stages of preparation. These findings have been showcased at numerous prestigious international conferences, enhancing scientific dialogue, and also presented at public-oriented events to bridge the gap between complex research and general understanding. To further popularize these insights, articles aimed at the general audience have been published, making the research accessible to a broader community. Moreover, the expertise developed during the project has been integrated into new educational courses for master's and engineering students.
The Mnemosyne project has made pivotal contributions to neuroscience, blending advanced methodologies with in-depth behavioral studies. This report details the project's key activities and findings, emphasizing their significance for both fundamental research and potential human applications.

1. Development of a New Sleep Scoring System: The project's development of a novel sleep scoring system based on brain activity, rather than observable behavior, marks a significant advancement. This method is particularly effective in analyzing sleep during periods of fear-induced immobility, common in fear learning scenarios. Implication: This approach offers a more accurate tool for studying sleep disorders in humans, particularly those associated with trauma or stress, thus enhancing the understanding and treatment of such conditions.
2. Real-Time Position Decoding Algorithm: The development of a deep learning-based algorithm for real-time position decoding has been a technological breakthrough. This tool can decode actual and "dreamed" positions during wakefulness and sleep. Implication: Such technology has profound implications for human research, potentially aiding in the understanding of dream processes, memory consolidation during sleep, and the development of new treatments for sleep and memory disorders.
3. Role of Breathing in Fear Response: Our research uncovered that breathing not only responds to but actively modulates brain activity during fear reactions. This finding shifts the understanding of the physiological mechanisms in fear responses. Implication: This insight could inform breathing-based interventions for anxiety and panic disorders in humans, emphasizing how respiratory control can impact emotional regulation.
4. Umaze Task: Behavioral Analysis: The creation of the Umaze task allowed for a detailed study of various defense reactions (jumping, avoidance, thigmotaxis, risk assessment, freezing) in response to threats. Implication: This task models human anxiety and fear responses, providing a valuable framework for testing interventions and understanding human anxiety disorders on a fundamental level.
5. Insights into Sleep Counterconditioning: The Mnemosyne project's exploration of counterconditioning revealed its limitations in addressing the full spectrum of anxiety behaviors, particularly in aversive learning contexts. This finding is vital for the development of more effective exposure therapies for anxiety disorders. It suggests that such therapies need to address both the spatial and affective components of fear conditioning to ensure comprehensive treatment, highlighting the complexity of fear conditioning and the necessity for multifaceted therapeutic approaches.
Summary of the key experiment of the project