Genetic Influences on Brain Aging: Analyzing Sex Differences in the UK Biobank using Structural MRI

Brain aging trajectories differ between males and females, yet the genetic factors underlying these differences remain underexplored. Using structural MRI and genotyping data from 40,940 UK Biobank participants (aged 45-83), we computed Brain Age Gap Estimates (BrainAGE) for total brain, hippocampal, and ventricular volumes. We conducted sex-stratified genome-wide association studies (GWAS) and Post-GWAS analyses to identify genetic variants associated with accelerated brain aging. Distinct gene sets emerged by sex: in females, neurotransmitter transport and mitochondrial stress response genes were implicated; in males, immune and inflammation-related genes dominated. Shared genes, including GMNC and OSTN, were consistently linked to brain volumes across sexes, suggesting core roles in neurostructural maintenance. Tissue expression analyses revealed sex-specific enrichment in pathways tied to neurodegeneration. These findings highlight the importance of sex-stratified approaches in aging research and suggest genetic targets for personalized interventions against age-related cognitive decline.

Direct Estimation of Pediatric Heart Rate Variability from BOLD-fMRI: A Machine Learning Approach Using Dynamic Connectivity

In many pediatric fMRI studies, cardiac signals are often missing or of poor quality. A tool to extract Heart Rate Variation (HRV) waveforms directly from fMRI data, without the need for peripheral recording devices, would be highly beneficial. We developed a machine learning framework to accurately reconstruct HRV for pediatric applications. A hybrid model combining one-dimensional Convolutional Neural Networks (1D-CNN) and Gated Recurrent Units (GRU) analyzed BOLD signals from 628 ROIs, integrating past and future data. The model achieved an 8% improvement in HRV accuracy, as evidenced by enhanced performance metrics. This approach eliminates the need for peripheral photoplethysmography devices, reduces costs, and simplifies procedures in pediatric fMRI. Additionally, it improves the robustness of pediatric fMRI studies, which are more sensitive to physiological and developmental variations than those in adults.