Circuit dynamics of structuring episodic memories in humans

项目总结 我们的生活随着时间的推移而展开，将丰富、动态和多感官的信息编织成一种连续的体验。 然而，我们记得这是一系列离散事件。例如，对一部两小时电影的记忆 包括一些与主要故事相关的令人难忘的时刻。在编码过程中，我们分割异常事件并 关联相关事件。在检索过程中，我们利用编码事件之间的时间关联进行检索 以获取特定的内存信息。海马区(HPC)、前额叶皮质(PFC)和黑质(SN) 被认为支持认知计算(例如，概念预测、预测错误检测、时间 关联)，这对于情节记忆的编码和检索至关重要。然而，这三个地区如何 共同努力促进人类情节记忆的构建仍不清楚。建议进行的研究 旨在通过识别HPC-PFC-SN网络中的神经动力学并揭示电路级神经来解决此问题 事件分段的机制及其与人类情景记忆的关系。 中心假设是事件分段，这对情景记忆的形成和提取有影响， 产生于HPC感知预测和接收到的感觉输入之间的差异，即 由SN中的多巴胺能神经元跟踪，以更新存储在PFC中的事件模型。为了测试这一点，我将录制 HPC-PFC-SN网络中的单个神经元活动和局部场电位信号，而患者 为临床目的植入的深度电极，编码和检索半现实经验的记忆 由控制良好的视频剪辑创建。我还将建立一个计算模型，它可以严格地再现 观察到行为和神经特征。训练后的模型将用作HPC-PFC-SN的代理 网络，通过模拟来研究这个三方网络与记忆行为之间的因果联系 计算性“损伤”，这将为真正的电刺激提供有洞察力的指导。 为了实现拟议的目标，我将参加由不同领域的一组专家指导的培训，包括 术中记录(Ziv Williams博士和Adam Mamelak博士)，区域间神经分析 动力学和电刺激(Ueli Rutishauser博士)和计算建模(Gabriel Kreiman博士)。 从行为测量、侵入性神经记录到 无论是微观层面还是介观层面，计算建模和电刺激都将提供有价值的 有机会加强我们对人类情景记忆系统的了解。的预期结果 这项提议可能会促进记忆相关障碍的治疗干预的发展。

Project summary Our lives unfold over time, weaving rich, dynamic, and multisensory information into a continuous experience. However, we remember this as a series of discrete events. For example, the memory of a two-hour movie consists of a few memorable moments tied to the main story. During encoding, we segment deviant events and associate relevant events. During retrieval, we utilize the temporal association among encoded events to search for specific memory information. The hippocampus (HPC), prefrontal cortex (PFC) and substantia nigra (SN) are thought to support cognitive computations (i.e., conceptual prediction, prediction error detection, temporal association) that are critical for the encoding and retrieval of episodic memory. However, how these three regions work together to facilitate the construction of episodic memory in humans remains unclear. The proposed study aims to address this by identifying neural dynamics in the HPC-PFC-SN network and revealing circuit-level neural mechanisms of event segmentation and its relationship with human episodic memory. The central hypothesis is that event segmentation, which is influential in episodic memory formation and retrieval, emerges from the difference between the HPC perceptual predictions and received sensory inputs, which is tracked by dopaminergic neurons in the SN to update event models stored in the PFC. To test this, I will record both single neuron activity and local field potential signals in the HPC-PFC-SN network while patients, who have depth electrodes implanted for clinical purposes, encode, and retrieve the memory of semi-realistic experience created by well-controlled video clips. I will also build a computational model that can rigorously reproduce the observed behavioral and neural signatures. The trained model will be used as a proxy of the HPC-PFC-SN network to study the causal link between this tripartite network and memory behaviors by simulating computational “lesions”, which will provide insightful guidance for real electrical stimulation. To achieve the proposed goals, I will pursue training mentored by a group of experts in different fields, including the intraoperative recordings (Dr. Ziv Williams and Dr. Adam Mamelak), analyses of inter-regional neural dynamics and electrical stimulation (Dr. Ueli Rutishauser), and computational modeling (Dr. Gabriel Kreiman). The comprehensive analytic approaches spinning from behavior measurements, invasive neural recordings from both microscopic and mesoscopic levels, computational modeling and electrical stimulation will provide valuable opportunities to strengthen our understanding of human episodic memory system. The expected outcomes of this proposal will potentially advance the development of therapeutic interventions for memory-related disorders.