Hippocampal subfield contributions to episodic memory loss in amnesia

Hippocampal damage impairs episodic memory, but it is unknown precisely why.

Research in non-humans suggests that damage to a specific hippocampal subfield (cornu Ammonis 3, CA3) impairs computational processes called pattern separation (the ability to distinguish between similar but distinct memories; PS), and pattern completion (the ability to recall a full memory from partial cues; PC).

I have shown that focal bilateral human CA3 pathology causes extensive episodic amnesia alongside reduced functional connectivity between the hippocampus and episodic memory network.

Episodic amnesia could arise from disrupted PS/PC during learning and/or retrieval, or, from aberrant interactions between PS/PC and other cognitive processes supported by the hippocampus, critical to episodic re-experiencing (temporal sequencing, visuospatial re-experiencing).

This Fellowship will use functional MRI (fMRI) in a well-characterized cohort of patients to investigate the effects of CA3 pathology on episodic learning and retrieval.

Goals: - To understand how CA3 damage disrupts the normal hippocampal-cortical interactions required for episodic learning and retrieval. - To investigate whether episodic amnesia arises solely from a failure of PS/PC or from disrupted interactions between PS/PC and other processes such as temporal ordering or visuospatial re-experiencing. - To seek mechanistic understandings of how CA3 pathology disrupts episodic memory retrieval across the lifetime using fMRI.