Abstract 13203: Exercise Decreases Stress-Associated Neural Activity Predominantly by Upregulating Regulatory Medial Prefrontal Cortical Activity

Abstract

Introduction: Exercise associates with dose-dependent decreases in stress-associated neural activity (SNA) which, in part, mediate exercise’s beneficial impact on major adverse cardiovascular event (MACE) risk. SNA can be assessed as a ratio of the resting metabolic activity of the brain’s fear centers (i.e., the amygdala [Amyg]), to that of regulatory centers (i.e., the medial prefrontal cortex [PFC]). However, it is unknown whether exercise reduces SNA by impacting the activity of Amyg, mPFC, or both. Hypothesis: We tested whether exercise reduces SNA primarily through enhancing the activity of the mPFC. We further hypothesize that it is the regulatory effect of the mPFC on SNA that contributes to MACE risk reduction. Methods: Self-reported physical activity data were obtained from Partners Biobank participants and total metabolic equivalents-minutes per week (MET-min/wk) were calculated. In a subset with clinical 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging, Amyg and mPFC activity were measured and corrected by whole cerebrum activity. SNA was calculated (Amyg/mPFC activity). MACE and cardiovascular risk factors were obtained using International Classification of Diseases codes. Results: Out of 684 subjects with both physical activity and imaging data (median age 68 years [IQR 60,75]), 275 (40.2%) developed MACE. Physical activity (as tertiles) associated with a dose-dependent increase in mPFC activity (Figure 1A; standardized β [95% CI]: 0.087 [0.002,0.036], p=0.025). Moreover, while SNA predicted MACE in adjusted analysis, the activities of the Amyg or PFC alone did not (Figure 1B). Conclusions: Exercise associates with dose dependent increases in mPFC activity. This effect does not directly reduce MACE risk; however, it may reduce MACE risk via its regulatory action on SNA. These observations may also have relevance in the impact of exercise on depression/anxiety disorders and cognitive function.