Mediators of Physical Activity on Neurocognitive Function: A Review at Multiple Levels of Analysis

Abstract

Physical activity (PA) is known to maintain and improve neurocognitive health. However, there is still a poor understanding of the mechanisms by which PA exerts its effects on the brain and cognition in humans. Many of the most widely discussed mechanisms of PA are molecular and cellular and arise from animal models. While information about basic cellular and molecular mechanisms is an important foundation from which to build our understanding of how PA promotes cognitive health in humans, there are other pathways that could play a role in this relationship. For example, PA-induced changes to cellular and molecular pathways likely initiate changes to macroscopic properties of the brain and/or to behavior that in turn influence cognition. The present review uses a more macroscopic lens to identify potential brain and behavioral/socioemotional mediators of the association between PA and cognitive function. We first summarize what is known regarding cellular and molecular mechanisms, and then devote the remainder of the review to discussing evidence for brain systems and behavioral/socioemotional pathways by which PA influences cognition. It is our hope that discussing mechanisms at multiple levels of analysis will stimulate the field to examine both brain and behavioral mediators. Doing so is important, as it could lead to a more complete characterization of the processes by which PA influences neurocognitive function, as well as a greater variety of targets for modifying neurocognitive function in clinical contexts.

Intermittent metabolic switching, neuroplasticity and brain health

“…Evidence from human and animal studies has established that regular aerobic exercise can improve cognitive performance and can protect against anxiety and depression 18,19 . Cognitive challenges performed during exercise result in levels of enhancement of synaptic plasticity, as well as learning and memory, greater than either challenge alone 20 .…”

Physical activity as a model for health neuroscience

“…Most RCTs, however, assess either cognitive or brain changes resulting from exercise training. 2 This raises an important question regarding mechanisms of PA: are PA-related brain changes a necessary intermediary of PA-related cognitive changes or a meaningless byproduct of PA behavior? These questions can be answered via statistical mediation modeling.…”

“…In the brain-as-mediator model, PA-induced changes in brain structure or function are an intermediary outcome for changes in behavior. 2 Although it is self-evident that the brain must be mediating behavioral changes, it is not self-evident that changes in brain structure and function, as assessed through neuroimaging approaches, act as mediators for behavioral changes. It is possible that the most important brain changes resulting from PA are happening on the molecular and cellular levels and that these effects are not being detected or revealed by current neuroimaging techniques.…”

Neuroimaging, neuromodulation, and population health: the neuroscience of chronic disease prevention

“…191 In sum, there is promising evidence for the benefits of physical activity on brain health and its cognitive sequelae. We still have much to learn about the mediators of these effects [192][193][194] and moderators of the effects. 192,195 However, there is clear recognition that the effects of physical activity extend beyond cognitive function 196,197 and how physical activityinduced changes to the brain mediate changes in these and other behavioral outcomes is an important avenue for future research.…”