Cardiorespiratory fitness is associated with cortical thickness of medial temporal brain areas associated with spatial cognition in young but not older adults.

Cardiorespiratory fitness has a potent effect on neurocognitive health, especially regarding the hippocampal memory system. However, less is known about the impact of cardiorespiratory fitness on medial temporal lobe extrahippocampal neocortical regions. Specifically, it is unclear how cardiorespiratory fitness modulates these brain regions in young adulthood and if these regions are differentially related to cardiorespiratory fitness in young versus older adults. The primary goal of this study was to investigate if cardiorespiratory fitness predicted medial temporal lobe cortical thickness which, with the hippocampus, are critical for spatial learning and memory. Additionally, given the established role of these cortices in spatial navigation, we sought to determine if cardiorespiratory fitness and medial temporal lobe cortical thickness would predict greater subjective sense of direction in both young and older adults. Cross-sectional data from 56 young adults (20-35 years) and 44 older adults (55-85 years) were included. FreeSurfer 6.0 was used to automatically segment participants' 3T T1-weighted images. Using hierarchical multiple regression analyses, we confirmed significant associations between greater cardiorespiratory fitness and greater left entorhinal, left parahippocampal, and left perirhinal cortical thickness in young, but not older, adults. Left parahippocampal cortical thickness interacted with age group to differentially predict subjective sense of direction in young and older adults. Young adults displayed a positive, and older adults a negative, correlation between left parahippocampal cortical thickness and sense of direction. Our findings extend previous work on the association between cardiorespiratory fitness and hippocampal subfield structure in young adults to left medial temporal lobe neocortical regions.

Cardiorespiratory fitness is associated with fMRI signal in right cerebellum lobule VIIa Crus I and II during spatial navigation in older adult women.

Spatial navigation is a cognitive skill critical for accomplishing daily goal-directed behavior in a complex environment; however, older adults exhibit marked decline in navigation performance with age. Neuroprotective interventions that enhance the functional integrity of navigation-linked brain regions, such as those in the medial temporal lobe memory system, may preserve spatial navigation performance in older adults. Importantly, a well-established body of literature suggests that cardiorespiratory fitness has measurable effects on neurobiological integrity in the medial temporal lobes, as well as in other brain areas implicated in spatial navigation, such as the precuneus and cerebellum. However, whether cardiorespiratory fitness modulates brain activity in these regions during navigation in older adults remains unknown. Thus, the primary objective of the current study was to examine cardiorespiratory fitness as a modulator of fMRI activity in navigation-linked brain regions in cognitively healthy older adults. To accomplish this objective, cognitively intact participants (N = 22, aged 60-80 years) underwent cardiorespiratory fitness testing to estimate maximal oxygen uptake ( V · O2max) and underwent whole-brain high-resolution fMRI while performing a virtual reality navigation task. Our older adult sample demonstrated significant fMRI signal in the right and left retrosplenial cortex, right precuneus, right and left inferior parietal cortex, right and left cerebellum lobule VIIa Crus I and II, right fusiform gyrus, right parahippocampal cortex, right lingual gyrus, and right hippocampus during encoding of a virtual environment. Most importantly, in women but not men (N = 16), cardiorespiratory fitness was positively associated with fMRI activity in the right cerebellum lobule VIIa Crus I and II, but not other navigation-linked brain areas. These findings suggest that the influence of cardiorespiratory fitness on brain function extends beyond the hippocampus, as observed in other work, to the cerebellum lobule VIIa Crus I and II, a component of the cerebellum that has recently been linked to cognition and more specifically, spatial processing.

Cardiorespiratory fitness, hippocampal subfield volumes, and mnemonic discrimination task performance in aging.

Aging and exercise have opposing effects on mnemonic discrimination task performance, which putatively taxes pattern separation mechanisms reliant on the dentate gyrus (DG) subfield of the hippocampus. In young adults, increasing cardiorespiratory fitness (CRF) has been shown to improve mnemonic discrimination task performance and increase left anterior DG/CA3 volume. It is unknown how these variables interact in cognitive aging, yet this knowledge is critical, given the established effects of aging on hippocampal plasticity. To investigate these relationships, 65 older adults (aged 55-85 years) completed a submaximal treadmill test to estimate CRF, a mnemonic discrimination task, and a high-resolution MRI scan to determine hippocampal subfield volumes. Our older adult sample demonstrated the lowest task accuracy in the condition with the greatest stimuli similarity and left DG/CA3 body volume significantly predicted accuracy in this condition. Our results did not provide support for relationships between CRF and task accuracy or CRF and DG/CA3 volume as evidenced in studies of young adults. Instead, CRF predicted bilateral subiculum volume in older adult women, not men. Altogether, these findings provide further support for a role of the DG in behavioral pattern separation in humans and suggest that CRF may have differential effects on hippocampal subfield integrity in older adult men and women. ClinicalTrials.gov identifiers: (a) Neuroimaging Study of Exercise and Memory Function, NCT02057354; (b) The Entorhinal Cortex and Aerobic Exercise in Aging, NCT02775760; (c) Physical Activity and Cognition Study, NCT02773121.

Cardiorespiratory fitness predicts effective connectivity between the hippocampus and default mode network nodes in young adults.

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 (V. O2max ), 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 hippocampal effective connectivity provides a link between the rodent literature, which demonstrates a relationship between aerobic exercise and hippocampal plasticity, and the human literature, which demonstrates a relationship between aerobic exercise and CRF and the enhancement of broad cognitive domains including, but not limited to, memory.