Disentangling hippocampal and cortical contributions to episodic memory

项目摘要 本申请描述了一项为期5年的计划，旨在研究支持记忆失真的神经动力学， 将计算建模方法与功能性神经成像（fMRI）和非侵入性脑 刺激技术（TMS）。这位候选人是一位认知神经科学家， 巩固和经验的fMRI和TMS方法，寻求新的培训，在计算建模和 在安娜·夏皮罗博士和莎伦·汤普森-席尔博士的指导下进行基于模型的功能磁共振成像分析。的 培训将在提案的前2年进行（目标1），之后候选人将完成目标 2、作为一名独立研究员。拟议中的实验旨在填补我们理解中的一个关键空白 通过检查它们作为多个信息源的功能来研究记忆扭曲： 事件的具体细节，由海马支持，并受到更普遍的先验知识的影响， 由皮层区域支持。一个占主导地位的模型预测，同一记忆的不同版本是 海马体和皮层中储存的信息：分别是详细的版本和一般的，gist-like版本。 然而，目前还不清楚这些痕迹是否协调或竞争，以支持记忆，以及是否这样做。 互动是由认知和神经的限制。拟议的实验利用了最近 一个开发的空间记忆任务，其中动物和物体的位置是由它们的类别组织的 会员资格关键的是，提取可以分为两个部分：对图像位置的记忆 （误差的大小）和类别知识的影响（对同一类别图像的偏见）。 预计这两个措施将分别得到海马和皮层的支持， 候选人将通过开发一个神经网络来研究它们的动态相互作用是如何引起扭曲的 海马和皮质方面的模型。目标1提出了一个假设，即自然发生的 海马体和皮层在支持情景记忆方面是合作还是竞争， fMRI来测试模型的预测。目标2引入了一种因果操纵（TMS），以测试是否 对记忆系统的限制驱使海马体和皮层竞争编码新的记忆。 编码过程中的皮质破坏预计会增强海马功能，从而导致更准确的 记忆目标3将研究已知的整合机制（即内存重放）是否具有竞争力 优先保留海马和皮层记忆痕迹。一种新颖的行为操纵是 开发来转移重放，以优先考虑内存的特定或一般组件，这将被用于 评估其功能相关性。这些目标的完成将揭示海马的新见解- 导致记忆扭曲的皮层相互作用了解这些相互作用将有助于了解 他们的功能障碍如何导致病理学，并有可能帮助临床研究人员开发 治疗患有轻微记忆障碍的患者，如中风患者。

Project Summary This application describes a 5-year plan to investigate the neural dynamics that underpin distortion in memory, integrating computational modeling approaches with functional neuroimaging (fMRI) and non-invasive brain stimulation techniques (TMS). The candidate, a cognitive neuroscientist with a background in memory consolidation and experience in fMRI and TMS methods, seeks new training in computational modeling and model-based fMRI analysis under the mentorship of Dr. Anna Schapiro and Dr. Sharon Thompson-Schill. The training will take place in the first 2 years of the proposal (Aim 1), after which the candidate will complete Aims 2 and 3 as an independent researcher. The proposed experiments aim to fill a critical gap in our understanding of memory distortions by examining them as a function of multiple sources of information: memory for the specific details of the event, supported by the hippocampus, and influence by more general prior knowledge, supported by cortical regions. A predominant model predicts that different versions of the same memory are stored in the hippocampus and cortex: a detailed version, and a general, gist-like version, respectively. However, it is unclear whether these traces coordinate or compete in supporting memory and whether such interactions are shaped by cognitive and neural constraints. The proposed experiments make use of a recently developed spatial memory task in which the locations of animals and objects are organized by their category membership. Critically, retrieval can be separated into two components: memory for the image's location (magnitude of error) and the influence of category knowledge (bias towards images from the same category). Anticipating that these two measures will be supported by the hippocampus and cortex, respectively, the candidate will investigate how their dynamic interplay gives rise to distortions by developing a neural network model with hippocampal and cortical aspects. Aim 1 addresses the hypothesis that there is naturally occurring variation in whether the hippocampus and cortex cooperate or compete in supporting episodic memories, using fMRI to test predictions made by the model. Aim 2 introduces a causal manipulation (TMS) to test whether constraints to the memory system drive the hippocampus and cortex to compete to encode new memories. Cortical disruption during encoding is predicted to boost hippocampal function, leading to more accurate memory. Aim 3 will investigate whether known consolidation mechanisms (i.e. memory replay) competitively prioritize the retention of hippocampal and cortical memory traces. A novel behavioral manipulation is developed to shift replay to prioritize either specific or general components of a memory, and this will be used assess its functional relevance. Completion of these aims will reveal novel insights into the hippocampal- cortical interactions that give rise to distortions in memory. Understanding these interactions will shed light on how their dysfunction leads to pathology and has the potential to aid clinical researchers in the development of treatments for patients suffering from subtle impairments in memory, such as stroke patients.