Sex Differences in the Brain-Heart Axis and Cognitive Function: Insights from Heart Rate Variability

The brain-heart axis, a bidirectional communication system linking central neural and autonomic regulation with cardiovascular function, has emerged as a key framework for understanding cognitive performance, brain health, and resilience.This review synthesizes evidence published in the last 15 years to evaluate heart rate variability (HRV) as a noninvasive biomarker of brain-heart interactions and to examine the role of sex differences in this relationship.Across recent studies, HRV has been consistently associated with top-down regulation involving cortical regions, the amygdala, the insula, and the autonomic nervous system.Specific functional connectivity patterns were associated with vagally mediated HRV indices, suggesting a link between central neural networks and cardiac autonomic regulation.Recent neuroimaging studies further suggest that autonomic regulation differs by sex, with females showing greater recruitment of limbic and interoceptive regions, including the amygdala, and males demonstrating greater engagement of prefrontal regions involved in inhibitory control.Despite these differences, many studies continue to treat sex primarily as a statistical covariate rather than as a biological determinant.Evidence also indicates that brainheart coupling varies across physiological states, particularly during sleep, underscoring the dynamic nature of neurovisceral regulation.Collectively, these findings support incorporating sex as a fundamental biological variable within the neurovisceral integration model.We propose that a sex-informed framework of the brain-heartcognition axis may improve mechanistic understanding, strengthen the interpretation of HRV-based biomarkers, and inform more precise strategies for preserving cognitive health and reducing the risk of neurocognitive decline across the lifespan.