Motivated Memory as Therapeutic Target

描述（由申请人提供）：基于海马体和内侧颞叶的陈述性或情景记忆系统专门用于快速重新定位新的环境，支持行为的适当快速转变。令人惊讶的是，在认知治疗中利用这些机制的潜力仍未开发。我们已经证明，在奖励预期过程中，陈述性记忆系统和多巴胺能中脑的功能磁共振成像激活增加与即将到来的经验的记忆编码相关。我们的研究结果提出了一种方法和机制，使用“行为神经刺激”的多巴胺能系统，以启动海马学习。这种方法与精神药理学的传统范式形成对比，精神药理学的目标是神经调节系统的慢性平衡。这里，调整明确针对学习期间。我们提出了三个系列的实验，旨在1）使用实时功能磁共振成像测试中脑边缘激活本身和记忆编码成功之间的因果关系的存在; 2）证明这种现象对临床干预的适用性; 3）确定治疗过程中单个突出事件对行为的长期影响。我们希望这些研究能够为使用多巴胺系统的认知和行为调节来为大脑的适应性学习做好准备提供基础。 公共卫生相关性：我们建议通过增加多巴胺的释放来增强认知治疗期间的学习，多巴胺是一种已知的神经递质，可以在认知治疗的特定时间段内增强学习和新记忆的形成。我们计划在治疗前，从行为上刺激多巴胺系统。我们希望这些研究能够指导非药物的个体定制治疗的发展，以加强精神病学中基于学习的治疗。

DESCRIPTION (provided by applicant): Declarative or episodic memory systems based in the hippocampus and medial temporal lobes are specialized for rapid reorientation to new contexts, supporting appropriately rapid shifts in behavior. Surprisingly, the potential for leveraging these mechanisms in cognitive therapy remains untapped. We have demonstrated that increased fMRI activation of declarative memory systems together with dopaminergic midbrain during reward anticipation correlates with memory encoding for upcoming experience. Our findings suggest a method and mechanism for using "behavioral neurostimulation" of dopaminergic systems to prime the hippocampus for learning. This approach contrasts with conventional paradigms in psychopharmacology where the goal is chronic equilibrium of neuromodulatory systems. Here, the adjustment is explicitly targeted to the period of learning. We propose three series of experiments designed to 1) to test the existence of a causal relationship between mesolimbic activation per se and memory encoding success using real-time fMRI; 2) to demonstrate the suitability of this phenomenon to clinical interventions; and 3) determine long-term effects on behavior from the impact of a single salient episode in a therapeutic session. We expect these studies to provide a foundation for using cognitive and behavioral regulation of dopamine systems to prepare the brain for adaptive learning. PUBLIC HEALTH RELEVANCE: We propose to enhance learning during cognitive therapy by increasing the release of dopamine, a neurotransmitter known to enhance learning and new memory formation, during the specific time period of a cognitive therapy session. We plan to stimulate dopamine systems behaviorally, prior to therapy. We expect these studies to guide the development of non-drug, individually tailored treatments to enhance learning-based therapies in psychiatry.