# Multiscale Mechanisms of Exercise-Induced Neuroplasticity: From Molecular Pathways to Network Dynamics and Behavioral Adaptation

## TL;DR

Exercise improves brain plasticity through multiple levels, from molecular changes to brain network reorganization, with benefits for cognition and mental health.

## Contribution

This paper integrates multiscale mechanisms of exercise-induced neuroplasticity, emphasizing precision prescriptions for individual variability.

## Key findings

- Exercise activates BDNF signaling and mitochondrial adaptation, enhancing brain function.
- Acute exercise modulates neurochemistry, while chronic exercise promotes structural brain remodeling.
- Personal factors like genetics and environment influence exercise-induced neuroplasticity outcomes.

## Abstract

What are the main findings?
Exercise promotes neuroplasticity through a multiscale mechanism, integrating molecular pathways like BDNF signaling and mitochondrial adaptation with large-scale functional brain network reorganization.Distinct neural mechanisms underlie acute versus chronic exercise, where acute bouts trigger immediate neurochemical modulation while chronic training induces long-term structural remodeling and network homeostasis.

Exercise promotes neuroplasticity through a multiscale mechanism, integrating molecular pathways like BDNF signaling and mitochondrial adaptation with large-scale functional brain network reorganization.

Distinct neural mechanisms underlie acute versus chronic exercise, where acute bouts trigger immediate neurochemical modulation while chronic training induces long-term structural remodeling and network homeostasis.

What are the implications of the main findings?
Physical activity acts as a “multi-target” behavioral intervention capable of enhancing executive function, regulating emotions, and aiding rehabilitation in addiction and neurodegenerative disorders.To maximize therapeutic efficacy, clinical applications should adopt “precision exercise prescriptions” that account for individual variability in genetics, environment, and dose–response relationships.

Physical activity acts as a “multi-target” behavioral intervention capable of enhancing executive function, regulating emotions, and aiding rehabilitation in addiction and neurodegenerative disorders.

To maximize therapeutic efficacy, clinical applications should adopt “precision exercise prescriptions” that account for individual variability in genetics, environment, and dose–response relationships.

Exercise as a non-pharmacological measure is important to increase the brain plasticity hence improving cognitive performance as well as mental health. This narrative review describes in depth the hierarchical multiscale processes of neuroplasticity to exercise, including the presence of neurotrophic factor regulation, cellular metabolic adaptations and neurotransmitter remodeling, up to the structure and functional reorganization of brain networks as seen through neuroimaging, and concluding with adaptive cognitive and behavioral outcomes. We further investigate the role of personal variations in genetic time and social environments in moderating the neuroplasticity of exercise. Furthermore, the review identifies the importance of combining multimodal visualization methods with computational models in generating accurate workout prescriptions and their potential of translation into clinical and educational practice. Lastly, the research problems and “grand challenges” are addressed, with a focus on the importance of exercise as a pleiotropic behavior-intervention and its general implications to the area of promoting brain health.