Attenuating the stress-induced bias towards habit memory through hippocampal self- neuromodulation

压力可能对我们的健康和幸福有重要影响，部分原因是压力引起的认知变化。压力对学习和记忆过程的影响尤其有文献记载，表明压力不仅影响我们学习和记忆的多少，还影响我们学习的内容和学习的方式。特别是，压力促进了从依赖海马体的“认知”记忆向依赖背纹状体的“习惯”记忆的转变。这种转变被认为在精神疾病中起着重要的作用，其中失调的压力系统和异常的记忆过程都是突出的，比如创伤后应激障碍（PTSD）或成瘾。本项目的主要目的是测试海马体定向神经反馈（NF）旨在上调其活动的自我控制，是否可以用于加强应激下的“认知”记忆加工，从而减弱应激诱导的向依赖纹状体的“习惯”记忆的转变。为此，将在汉堡和特拉维夫进行两项实验，使用最先进的成像技术以及先进的机器学习和建模计算方法。在第一个实验中，健康的参与者将经历标准化的压力或控制程序，然后通过fMRI-NF（测试或假）训练来上调他们的海马体活动。之后，他们将在扫描仪中完成一个学习任务，该任务可以由海马体或背纹状体获得，从而揭示多个记忆系统的相对参与。在第二个实验中，同时进行的fMRI/EEG记录将用于开发fMRI海马活动的电子指纹（EFP）。该EFP在概率分类学习过程中调节多个记忆系统参与的能力将在另一个（试点）实验中进行测试。该项目将为压力对学习和记忆的影响的理论和临床方面提供新的见解。从理论的角度来看，它将为压力对学习和记忆的影响，特别是多记忆系统的参与，提供大脑机制的因果推理。从临床角度来看，它将指出如何抵消应激对认知的影响的新途径，同时使用可扩展的新颖计算方法进行非侵入性局部神经调节。因此，这项研究可能对教育和/或与工作相关的环境，最重要的是，对与压力相关的精神障碍具有重要意义。这将是来自汉堡和特拉维夫的pi的联合项目，他们在压力，记忆和神经成像研究方面带来了独特的能力，这些能力的结合对于这个开创性项目的成功至关重要。

Stress may have a critical impact on our health and well-being, partly due to stress-induced changes in cognition. Stress effects on learning and memory processes are particularly well documented, showing that stress not only affects how much we learn and remember but also what and how we learn. In particular, stress promotes a shift from hippocampus-dependent ‘cognitive’ memory to dorsal striatum-dependent ‘habit’ memory. This shift is thought to play an important role in mental disorders in which both dysregulated stress systems and aberrant memory processes are prominent, such as post-traumatic stress disorder (PTSD) or addiction. The primary objective of the present project is to test whether hippocampus targeted neurofeedback (NF) aimed to upregulate self-control over its activity can be used to strengthen ‘cognitive’ memory processing under stress and hence attenuate the stress-induced shift towards striatum-dependent ‘habit’ memory. To this end, two experiments will be conducted in Hamburg and Tel Aviv, using state-of-the-art imaging techniques along with advanced computational methods of machine learning and modelling. In a first experiment, healthy participants will undergo a standardized stress or control procedure before they are trained via fMRI-NF (test or sham) to upregulate their hippocampus activity. Thereafter, they will complete a learning task, in the scanner, that can be acquired by the hippocampus or the dorsal striatum and thus reveals the relative engagement of multiple memory systems. In a second experiment, simultaneous fMRI/EEG recording will be used to develop an Electrical-Finger Print (EFP) of the fMRI hippocampal activity. The capacity of this EFP to modulate the engagement of multiple memory systems during probabilistic classification learning will be tested in an additional (pilot) experiment. This project will provide novel insights into the theoretical and clinical aspects of stress effects on learning and memory. From a theoretical perspective, it will provide causal inference to brain mechanisms underlying stress effects on learning and memory, in particular the engagement of multiple memory systems. From a clinical perspective, it will point to new avenues of how stress effects on cognition can be counteracted, while using a scalable novel computational approach for non-invasive localized neural modulation. The study may thus have critical implications for educational and/or work-related settings and, most importantly, for stress-related mental disorders. This will be a joint project of PIs from Hamburg and Tel Aviv who bring in unique capabilities in stress, memory and neuroimaging research, the combination of which is essential for the success of this ground-breaking project.