Cardiorespiratory fitness is associated with enhanced hippocampal functional connectivity in healthy young adults

Abstract

Consistent associations have been found between higher cardiorespiratory fitness (CRF) and indices of enhanced brain health and function, including behavioral measures of cognition as well as neuroimaging indicators such as regional brain volume. Several studies have reported that higher CRF levels are associated with a larger hippocampus, yet associations between volume and memory or functional connectivity metrics remain poorly understood. Using a multi-modal framework, we hierarchically examine the association between CRF and hippocampal volume and resting state functional connectivity (rsFC) in younger adults, as well as their relationship between with memory function. We conducted theoretically-driven analyses with seeds in the anterior and posterior hippocampus, as well as control seeds in the caudate nucleus. We tested whether (1) hippocampal connectivity with prefrontal cortical regions was associated with CRF in an adult sample much younger than traditionally tested, (2) associations between CRF and rsFC remain significant after adjusting for volume, and (3) volume and rsFC are related to memory. We found that higher CRF levels were associated with larger anterior hippocampal volume and more positive rsFC of the anterior hippocampus to several regions including the prefrontal cortex. rsFC also accounted for significant variance in CRF, above and beyond volume. CRF can thus be independently linked to increased anterior hippocampal volume, as well as stronger hippocampal rsFC in a population much younger than those typically tested, suggesitng it is critical to maintainig multiple aspects of brain health.

Keywords: cardiorespiratory fitness; functional connectivity; hippocampal subfield; resting state.

Figure 1

Location of the hippocampal and caudate seed regions in each hemisphere derived from FIRST segmentation. The seed masks are presented on a representative subject’s MPRAGE. Green: Left posterior hippocampus; Yellow: Left anterior hippocampus; Red = Right posterior hippocampus; Blue = Right anterior hippocampus; Cyan = Left caudate; Teal = Right caudate.

Figure 2

Positive correlation between left anterior hippocampal volume and cardiorespiratory fitness (V0_2max) in healthy younger adults.

Figure 3

Positive correlations between resting state connectivity of the anterior and posterior hippocampus seeds and cardiorespiratory fitness (V0_{2max score}) in healthy younger adults. Panel (A) depicts results from the left anterior hippocampus seed. (B) depicts (NS) results from the left posterior hippocampal seed. Panel (C) depicts results from the right anterior seed, and (D) results from the right posterior hippocampal seed. Representative scatter plots are presented for clusters 2 and 7. Numbers in blue within each panel correspond to the cluster labels in Table 1. Clusters 5 and 6 are not visible in panel C. Results were corrected based on the voxel z-score and extent of activity given the correlated nature of the voxels. Specifically, the voxel-wise z-score was 2.3 (p<.01) and the clusters were significant at p<.05).