Disentangling hippocampal and cortical contributions to episodic memory

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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.