Differences in directed functional brain connectivity related to age, sex and mental health

Objective: Functional interconnections between brain regions define the 'connectome' which which is of central interest for understanding human brain function. Resting-state functional magnetic resonance (rsfMRI) work has revealed changes in static connectivity related to age, sex, cognitive abilities and psychiatric symptoms, yet little is known how these factors may alter the information flow. The commonly used approach infers functional brain connectivity using stationary coefficients yielding static estimates of the undirected connection strength between brain regions. Dynamic graphical models (DGMs) are a multivariate model with dynamic coefficients reflecting directed temporal associations between nodes, and can yield novel insight into directed functional connectivity. Here, we leveraged this approach to test for associations between edge-wise estimates of direction flow across the brain connectome and age, sex, intellectual abilities and mental health. Methods: We applied DGM to investigate patterns of information flow in data from 984 individuals from the Human Connectome Project (HCP) and 10,249 individuals from the UK Biobank. Results: Our analysis yielded patterns of directed connectivity in independent HCP and UK Biobank data similar to those previously reported, including that the cerebellum consistently receives information from other networks. We show robust associations between information flow and age and sex for several connections, with strongest effects of age observed in the sensorimotor network. Visual, auditory and sensorimotor nodes were also linked to mental health. Discussion: Our findings support the use of DGM as a measure of directed connectivity in rsfMRI data and provide new insight into the shaping of the connectome during aging. ### Competing Interest Statement The authors have declared no competing interest.

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