Functional Characterization of the Human Hippocampal Long Axis Using Within-Individual Precision Neuroimaging

Abstract

This dissertation describes my efforts towards a precise network-informed functional characterization of the human hippocampal long axis, made possible by advances in within-individual precision human neuroimaging. In the Introduction, I describe foundational work that has proposed the differential involvement of hippocampal regions in diverse cognitive functions including episodic memory, spatial reasoning, and assessing novelty. While a definitive account of hippocampal function will remain elusive, I will argue it is both conceptually important and experimentally useful to study the functional roles of the hippocampus in the context of associated networks precisely estimated in cerebral cortex. The first two chapters highlight the neuroimaging techniques necessary for precisely estimating hippocampal network organization and function. These chapters focus on the cerebellum, in part because that was my own introduction to these methods, but also because these methods’ success given the cerebellum’s polysynaptic connectivity to cortex and fine structural details strengthens the case for their use in the hippocampus. Chapter 1 uses functional neuroimaging techniques to explore the organization of the human cerebellum based on network functional connectivity. Chapter 2 applies within-individual neuroimaging of the cerebellum to simple motor tasks. In both cases, exploring a small set of densely sampled individuals allowed all analyses to respect each participant’s idiosyncratic anatomy, improving resolution and allowing for the characterization of functional and organizational details that would have been missed using approaches which spatially average data across participants. Chapter 3 applies these techniques to the hippocampal long axis across two independent sets of densely sampled individuals. We first demonstrate differential functional connectivity from the anterior and posterior hippocampus to distinct cerebral networks DN-A and SAL / PMN, respectively. Task data then reveals a double-dissociation: the anterior hippocampus is preferentially involved in the construction of mental scenes, while the posterior hippocampus displays transient activation in response to salient stimuli. These parallel dissociations in functional connectivity and cognitive function position the anterior and posterior hippocampus as separable components of broader brain networks and refines our understanding of hippocampal contributions to human cognition.