Converging evidence suggests a relationship between aerobic exercise and hippocampal neuroplasticity that interactively impacts hippocampally dependent memory.The majority of human studies have focused on the potential for exercise to reduce brain atrophy and attenuate cognitive decline in older adults, whereas animal studies often center on exercise-induced neurogenesis and hippocampal plasticity in the dentate gyrus (DG) of young adult animals. In the present study, initially sedentary young adults (18-35 years) participated in a moderate-intensity randomized controlled exercise intervention trial (ClinicalTrials.gov; NCT02057354) for a duration of 12 weeks. The aims of the study were to investigate the relationship between change in cardiorespiratory fitness (CRF) as determined by estimated _ VO 2MAX , hippocampally dependent mnemonic discrimination, and change in hippocampal subfield volume.Results show that improving CRF after exercise training is associated with an increased volume in the left DG/CA3 subregion in young adults. Consistent with previous studies that found exercise-induced increases in anterior hippocampus in older adults, this result was specific to the hippocampal head, or most anterior portion, of the subregion. Our results also demonstrate a positive relationship between change in CRF and change in corrected accuracy for trials requiring the highest level of discrimination on a putative behavioral pattern separation task. This relationship was observed in individuals who were initially lower-fit, suggesting that individuals who show greater improvement in their CRF may receive greater cognitive benefit. This work extends animal models by providing evidence for exercise-induced neuroplasticity specific to the neurogenic zone of the human hippocampus.

Rodent and human studies examining the relationship between aerobic exercise, brain structure, and brain function indicate that the hippocampus (HC), a brain region critical for episodic memory, demonstrates striking plasticity in response to exercise.Beyond the hippocampal memory system, human studies also indicate that aerobic exercise and cardiorespiratory fitness (CRF) are associated with individual differences in large-scale brain networks responsible for broad cognitive domains. Examining network activity in large-scale resting-state brain networks may provide a link connecting the observed relationships between aerobic exercise, hippocampal plasticity, and cognitive enhancement within broad cognitive domains. Previously, CRF has been associated with increased functional connectivity of the default mode network (DMN), specifically in older adults. However, how CRF relates to the magnitude and directionality of connectivity, or effective connectivity, between the HC and other DMN nodes remains unknown. We used resting-state fMRI and conditional Granger causality analysis (CGCA) to test the hypothesis that CRF positively predicts effective connectivity between the HC and other DMN nodes in healthy young adults.Twenty-six participants (ages 18-35 years) underwent a treadmill test to determine CRF by estimating its primary determinant, maximal oxygen uptake (VO 2max ), and a 10-min resting-state fMRI scan to examine DMN effective connectivity. We identified the DMN using group independent component analysis and examined effective connectivity between nodes using CGCA. Linear regression analyses demonstrated that CRF significantly predicts causal influence from the HC to the ventromedial prefrontal cortex, posterior cingulate cortex, and lateral temporal cortex and to the HC from the dorsomedial prefrontal cortex. The observed relationship between CRF and Corey A. Kronman and Kathryn L. Kern share the first authorship.

Previous neuroimaging studies support a role for the medial temporal lobes in maintaining novel stimuli over brief working memory (WM) delays, and suggest delay period activity predicts subsequent memory. Additionally, slice recording studies have demonstrated neuronal persistent spiking in entorhinal cortex, perirhinal cortex (PrC), and hippocampus (CA1, CA3, subiculum). These data have led to computational models that suggest persistent spiking in parahippocampal regions could sustain neuronal representations of sensory information over many seconds. This mechanism may support both WM maintenance and encoding of information into long term episodic memory. The goal of the current study was to use high-resolution fMRI to elucidate the contributions of the MTL cortices and hippocampal subfields to WM maintenance as it relates to later episodic recognition memory. We scanned participants while they performed a delayed match to sample task with novel scene stimuli, and assessed their memory for these scenes post-scan. We hypothesized stimulus-driven activation that persists into the delay period—a putative correlate of persistent spiking—would predict later recognition memory. Our results suggest sample and delay period activation in the parahippocampal cortex (PHC), PrC, and subiculum (extending into DG/CA3 and CA1) was linearly related to increases in subsequent memory strength. These data extend previous neuroimaging studies that have constrained their analysis to either the sample or delay period by modeling these together as one continuous ongoing encoding process, and support computational frameworks that predict persistent activity underlies both WM and episodic encoding.

It is well‐established that physical exercise and cardiorespiratory fitness are beneficial to brain health. Cardiorespiratory fitness (CRF) can attenuate both the neurobiological and cognitive consequences of age‐related decline. Although rodent research has provided strong evidence that exercise positively affects the neuronal system involved in learning and memory, human research has mostly focused on the effect of exercise and CRF on executive function, rather than hippocampal and entorhinal cortex (EC)‐dependent memory function. In a cross‐sectional study using established behavioral tasks known to recruit the hippocampus and EC and structural MRI of healthy older adults, we tested the following hypotheses: (1) CRF levels are positively associated with hippocampus‐dependent memory task performance; (2) CRF levels are positively associated with the structure of the hippocampus and EC. Healthy older adult (age 55–85 years, N = 23) underwent a standard graded submaximal treadmill test to determine CRF (Modified‐Balke protocol to estimate VO2max). FreeSurfer MRI analytic software was used to calculate cortical thickness and volume of T1‐weighted MR images. A multiple linear regression model showed that greater aerobic fitness was associated with greater volumes in the left and right hippocampus, but not with EC thickness or behavioral task performance. Our results indicate that higher fitness predicts greater hippocampal volume and therefore may be protective against loss of hippocampal volume with aging.Support or Funding InformationR00 AG 036845This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

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