Revealing the spatial pattern of brain hemodynamic sensitivity to healthy aging through sparse DCM

Age-related changes in the BOLD response could reflect neuro-vascular coupling modifications rather than simply impairments in neural functioning. In this study, we propose the use of a generative dynamic causal model (DCM) to decouple neuronal and vascular factors in the BOLD signal, with the aim of characterizing the whole-brain spatial pattern of hemodynamic sensitivity to healthy aging, as well as to test the role of hemodynamic features as independent predictors in an age-classification model.In this view, DCM was applied to the resting-state fMRI data of a cohort of 126 healthy individuals in a wide age range, providing reliable estimates of the hemodynamic response function (HRF) for each subject and each region of interest. Then, some features characterizing each HRF curve were extracted and used to fit a multivariate logistic regression model to predict the age class of each individual. Ultimately, we tested the final predictive model on an independent dataset of 338 healthy subjects selected from the Human Connectome Project Aging (HCP-A) and Development (HCP-D) cohorts. Our results entail the spatial heterogeneity of the age effects on the hemodynamic component, since its impact resulted to be strongly region- and population-specific, discouraging any space-invariant corrective procedures that attempt to correct for vascular factors when carrying out functional studies involving groups with different ages. Moreover, we demonstrated that a strong interaction exists between some specific hemodynamic features and age, further supporting the essential role of the hemodynamic factor as independent predictor of biological aging, rather than a simple confounding variable. Significance statement By inferring region-wise hemodynamic profiles at the individual level, this is the first study providing an exhaustive whole-brain characterization of the hemodynamic sensitivity to healthy aging, reporting further evidence of the vascular changes across the adult lifespan. Using a predictive framework, we analysed the statistical influence of advancing age on individual regional hemodynamic attributes, offering a quantitative evaluation of the diverse hemodynamic bias across different brain regions. We unveiled a specific set of hemodynamic predictors to discriminate young from elderly people, mainly describing vascular properties of right-hemispheric areas. This suggests the asymmetric nature of vascular degeneration processes affecting the human brain at the latest stage of life, other than a potential biomarker that could be relevant for brain-age prediction. ### Competing Interest Statement The authors have declared no competing interest.