Pattern Separation and Generalization in the Hippocampus

尽管大量证据表明海马体在陈述性记忆中起着重要作用，但海马体内部的个体结构对记忆的影响方式仍然是当前争论的话题。本研究的中心目标是评估海马子区回路的差异如何转化为支持情景记忆形成的功能差异。在形成新记忆的过程中，海马体被认为将相关的输入模式分离成不同的表征，从而最大限度地减少相似记忆痕迹之间的干扰。然而，来自神经网络模型和动物研究的发现表明，海马体内部存在张力，因此一些子场容易导致模式分离，而其他子场则倾向于在相似的输入模式中进行概括。利用高分辨率功能磁共振成像（fMRI），本研究旨在评估人类海马体子区在响应项目和项目间相似性操作时支持非重叠与共享记忆表征形成的程度。此外，为了补充这种高空间分辨率的功能磁共振成像方法，将直接记录人类海马的局部场电位，以更好地表征模式分离和概化的时间分布。描绘海马体子区介导记忆的方式将推进海马体功能的机制描述，并提供对表现出模式分离缺陷的人群（如老年人和精神分裂症患者）受影响的大脑区域的见解。

Although an impressive amount of evidence has emerged supporting a fundamental role for the hippocampus in declarative memory, the manner in which individual structures within the hippocampus contribute to memory remains a current topic of debate. The central objective of this proposal is to evaluate how differences in circuitry among hippocampal subfields translate to functional differences in support of episodic memory formation. In forming new memories, the hippocampus is thought to separate related input patterns into distinct representations, thereby minimizing interference between similar memory traces. However, findings from neural-network models and animal studies suggest that tension exists within the hippocampus such that some subfields readily contribute to pattern separation, whereas others tend to generalize across similar input patterns. Using high-resolution functional magnetic resonance imaging (fMRI), the proposed research aims to evaluate the degree to which human hippocampal subfields support the formation of non-overlapping vs. shared memory representations in response to similarity manipulations at both the item and inter-item level. Furthermore, to complement this high spatial resolution fMRI approach, local field potentials will be directly recorded from the human hippocampus to better characterize the temporal profile of pattern separation and generalization. Delineating the manner in which hippocampal subfields mediate memory will advance mechanistic accounts of hippocampal function, as well as provide insights into brain regions affected in populations exhibiting pattern separation deficits, such as older adults and individuals with schizophrenia.