The effect of external stimulation on functional networks in the aging healthy human brain

Abstract

Understanding the brain changes occurring during aging can provide new insights for developing treatments that alleviate or reversecognitive decline. Neurostimulation techniques have emerged as potential treatments for brain disorders and to improve cognitivefunctions. Nevertheless, given the ethical restrictions of neurostimulation approaches, in silico perturbation protocols based oncausal whole-brain models are fundamental to gaining a mechanistic understanding of brain dynamics. Furthermore, this strategycould serve to identify neurophysiological biomarkers differentiating between age groups through an exhaustive exploration of theglobal effect of all possible local perturbations. Here, we used a resting-state fMRI dataset divided into middle-aged (N =310, <65years) and older adults (N =310, ≥65) to characterize brain states in each group as a probabilistic metastable substate (PMS) space.We showed that the older group exhibited a reduced capability to access a metastable substate that overlaps with the rich club.Then, we fitted the PMS to a whole-brain model and applied in silico stimulations in each node to force transitions from the brainstates of the older- to the middle-aged group. We found that the precuneus was the best stimulation target. Overall, these findingscould have important implications for designing neurostimulation interventions for reversing the effects of aging on whole-braindynamics.