Mapping the Cerebello-Hippocampal Circuit: Normative Patterns and Sex-Dependent Connectivity
Cerebello hippocampal (CBHP) interactions have been implicated in spatial abilities and reinforcement learning, yet their relationship to behavior and differences in connectivity with sex in early adulthood are unclear. Resting CBHP network patterns have yet to be established in young adults. Mapping the normative resting-state CBHP connectivity pattern is essential for identifying when CBHP circuitry becomes behaviorally relevant across the lifespan and for detecting early circuit-level deviations that may precede neurodegenerative or endocrine disruption. We combined resting-state functional MRI (rsfMRI) with measures of cognition in 1,081 healthy young adults (22 to 37 years, 54% women) from the Human Connectome Project S1200 to map CBHP functional connectivity (FC), examine sex differences, and define its relationship with performance across episodic memory, visuospatial, and executive function tasks. Region of interest (ROI)-to-ROI FC between the right cerebellum and left hippocampus were quantified. In our CB-HP mapping, we found: 1) negative relationships between the entire HP axis and cerebellar regions: vermis VII; lobules VI, VIIb, and VIII; Crus I & II, and 2) positive relationships between most of the HP axis and ventral/medial cerebellar regions. We revealed sex differences in CB-HP such that females had greater FC than males between anterior to mid-hippocampal regions and medial cerebellar regions: vermis IV-VI; lobules VI, VIII, IX; and Crus II. We predicted CBHP FC patterns would show strong positive associations with cognitive measures (i.e., episodic memory, visuospatial processing, working memory, and executive function); however, we did not find any associations after multiple comparisons correction (pFDR > 0.05). Together, our findings detail a functional atlas of the CBHP circuit in young adulthood and highlight sex differences within. Our results provide a foundation for understanding functionally based gradients between these two regions.