A functional connectome signature of blood pressure in >30 000 participants from the UK biobank

Elevated blood pressure (BP) is a prevalent modifiable risk factor for cardiovascular diseases and contributes to cognitive decline in late life. Despite the fact that functional changes may precede irreversible structural damage and emerge in an ongoing manner, studies have been predominantly informed by brain structure and group-level inferences. Here, we aim to delineate neurobiological correlates of BP at an individual level using machine learning and functional connectivity.Based on whole-brain functional connectivity from the UK Biobank, we built a machine learning model to identify neural representations for individuals' past (∼8.9 years before scanning, N = 35,882), current (N = 31,367), and future (∼2.4 years follow-up, N = 3,138) BP levels within a repeated cross-validation framework. We examined the impact of multiple potential covariates, as well as assessed these models' generalizability across various contexts.The predictive models achieved significant correlations between predicted and actual systolic/diastolic BP and pulse pressure while controlling for multiple confounders. Predictions for participants not on antihypertensive medication were more accurate than for currently medicated patients. Moreover, the models demonstrated robust generalizability across contexts in terms of ethnicities, imaging centers, medication status, participant visits, gender, age, and BMI. The identified connectivity patterns primarily involved the cerebellum, prefrontal, anterior insula, anterior cingulate cortex, supramarginal gyrus, and precuneus, which are key regions of the central autonomic network, and involved in cognition processing and susceptible to neurodegeneration in Alzheimer's disease. Results also showed more involvement of default mode and frontoparietal networks in predicting future BP levels and in medicated participants.This study, based on the largest neuroimaging sample currently available and using machine learning, identifies brain signatures underlying BP, providing evidence for meaningful BP-associated neural representations in connectivity profiles.