Brain Controllability of Cognitive Control Networks is Associated with Executive Functions in Older Adults

Abstract Background Executive functions encompass effortful top‐down cognitive processes crucial for daily functioning. They are particularly vulnerable to aging in older adults and are often affected early in the course of Alzheimer’s disease. However, the neural mechanisms underlying aging‐related decline in executive functions are not well understood. Modal controllability is a structural metric quantifying the ease at which brain regions can move the brain into difficult‐to‐reach states with substantial effort to support diverse cognitive processes. The emphasis on effortful state transitions bears strong similarity to the definition of executive functions as effortful cognitive processes, rendering modal controllability as a putative neural substrate of executive function. Controllability has been associated with cognitive performance in younger populations, but no studies have examined controllability in older adults or its association with executive function over time. Method We used diffusion MRI (dMRI) data from community‐dwelling men ages 56‐70 (N=264 Time 2, N=104 Both Time 1 & 2) in the Vietnam Era Twin Study of Aging (VETSA).We performed whole‐brain deterministic fiber tracking on dMRI data to reconstruct white matter streamlines, which were then used to build structural connectivity matrices. Network‐level modal controllability of two cognitive control networks (multiple demand system and control network) were computed from connectivity matrices. An executive function factor score was computed based on six well‐established neuropsychological tasks: Stroop, Trail Making Test, Category Switching, Letter‐Number Sequencing, Reading Span, and Digit Span. Results In cross‐sectional analyses controlling for age, health status, ethnicity, and young adult general cognitive ability, modal controllability of cognitive control networks was positively associated with executive function at Time 2. Change in controllability from Time 1 to Time 2 (∼6 years) was positively associated with change in executive function over the same period. Conclusion Findings suggest that a putative mechanism of cognitive aging may involve the controllability of structural networks in supporting brain functional dynamics necessary for cognition. In particular, the longitudinal association suggests that structural network changes in controllability may be a key mechanism underlying aging‐related decline in executive function. A next step will be to how such changes are related to risk for mild cognitive impairment and Alzheimer’s dementia.