Rapid stimulation of human dentate gyrus function with acute mild exercise

Abstract

Physical exercise has beneficial effects on neurocognitive function, including hippocampus-dependent episodic memory. Exercise intensity level can be assessed according to whether it induces a stress response; the most effective exercise for improving hippocampal function remains unclear. Our prior work using a special treadmill running model in animals has shown that stress-free mild exercise increases hippocampal neuronal activity and promotes adult neurogenesis in the dentate gyrus (DG) of the hippocampus, improving spatial memory performance. However, the rapid modification, from mild exercise, on hippocampal memory function and the exact mechanisms for these changes, in particular the impact on pattern separation acting in the DG and CA3 regions, are yet to be elucidated. To this end, we adopted an acute-exercise design in humans, coupled with high-resolution functional MRI techniques, capable of resolving hippocampal subfields. A single 10-min bout of very light-intensity exercise (30%[Formula: see text]) results in rapid enhancement in pattern separation and an increase in functional connectivity between hippocampal DG/CA3 and cortical regions (i.e., parahippocampal, angular, and fusiform gyri). Importantly, the magnitude of the enhanced functional connectivity predicted the extent of memory improvement at an individual subject level. These results suggest that brief, very light exercise rapidly enhances hippocampal memory function, possibly by increasing DG/CA3-neocortical functional connectivity.

Keywords: episodic memory; functional MRI; hippocampus; pattern separation; physical exercise.

Fig. 1.

(A) Outline of the experimental procedures. Participants performed 10 min of exercise or rested (CTL) on different experimental days. After that, the study phase of the mnemonic discrimination task was administered. Participants waited ∼45 min before performing the test phase, an old−similar−new judgment task using targets, foils, and similar lures to which hippocampal pattern separation is particularly sensitive. (B) Discrimination performance assessed by the LDI for high, medium, and low mnemonic similarity bins. Mild exercise improved the LDI for the high- and medium-similarity bins compared with the CTL condition. *P < 0.05. (C) Increased psychological arousal levels positively correlated with LDI improvement in high-similarity lures.

Fig. 2.

Neural activity profiles in (A) the hippocampus and (B) other ROIs. Values indicate the critical pattern separation contrast of fMRI signals (lure CRs minus lure FAs). Of all hippocampal subfields, the EC and PHC exhibited higher levels of activation during the EX condition compared with the CTL condition. *P < 0.05. (C) Coronal view of ROI segmentation on a custom group template. Representative slices are shown from top to bottom in the anterior−posterior direction, and ROI demarcations are represented based on the color key displayed below. Note: PRC, perirhinal cortex; SUB, subiculum; TempPole, temporal pole.

Fig. 3.

Results of PPI analyses. (Upper) Voxels within cortical regions with significantly higher context-dependent (lure CRs) correlations with the hippocampal DG/CA3 in the EX condition compared with the CTL condition. (Lower) Significant correlations between the extent of PPI connectivity of the DG/CA3 with the specified cortical region and the enhancement in the LDI resulting from exercise. These brain−behavior relationships are observed in the left angular gyrus, left fusiform gyrus, and left parahippocampal gyrus.