Disentangling hippocampal and cortical contributions to episodic memory

项目摘要 这项申请描述了一个五年计划，以研究支撑记忆扭曲的神经动力学， 将计算建模方法与功能神经成像(FMRI)和非侵入性脑功能相结合 刺激技术(TMS)。候选人是一位有记忆背景的认知神经学家 巩固和积累了fMRI和TMS方法的经验，寻求在计算建模和 在Anna Schapiro博士和Sharon Thompson-Schill博士的指导下进行的基于模型的fMRI分析。这个 培训将在计划的前两年(目标1)进行，之后候选人将完成目标 2和3作为独立研究员。拟议中的实验旨在填补我们在认识上的一个关键空白 通过将记忆扭曲作为多个信息源的函数来研究它们：记忆 事件的具体细节，由海马体支持，并受到更一般的先验知识的影响， 由大脑皮层区域支持。一种主要的模型预测同一存储器的不同版本是 储存在海马体和皮质：分别是一个详细的版本和一个一般的、类似主旨的版本。 然而，目前尚不清楚这些痕迹在支持记忆方面是否协调或竞争，以及是否如此 相互作用是由认知和神经制约决定的。拟议的实验利用了最近的一项 发展的空间记忆任务，其中动物和物体的位置按其类别进行组织 会员制。关键的是，检索可以分为两个部分：图像位置的记忆 (误差的大小)和类别知识的影响(对来自同一类别的图像的偏见)。 预计这两项措施将分别由海马体和大脑皮层支持， 考生将通过开发神经网络来研究它们的动态相互作用如何导致扭曲 包括海马区和大脑皮层的模型。目标1解决了这样的假设，即存在自然发生 在支持情节记忆方面，海马体和皮质是否合作或竞争的差异，使用 FMRI来测试该模型所做的预测。目标2引入因果操纵(TMS)来测试 记忆系统的限制驱使海马体和大脑皮层竞争编码新的记忆。 据预测，编码过程中的皮质破坏会促进海马体功能，从而导致更准确的 记忆。目标3将调查已知的整合机制(即内存重放)是否具有竞争性 优先保留海马区和大脑皮层的记忆痕迹。一种新的行为操纵是 开发用于转移重放以确定存储器的特定或一般组件的优先级，这将被使用 评估其功能相关性。完成这些目标将揭示对海马体的新见解- 导致记忆扭曲的大脑皮层相互作用。了解这些相互作用将有助于 它们的功能障碍如何导致病理，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.