Abstract
Abstract The human brain undergoes both significant structural and functional changes across the lifespan. It is important to understand the underlying causal relationship of the emerging dynamical changes in functional connectivity with age. On average, functional connectivity within resting-state networks weakens in magnitude while connections between resting-state networks tend to increase with age. Further, few recent studies show that effective connectivity within and between large scale resting-state functional networks changes over the healthy lifespan. Motivated by these findings we move one step forward to investigate the effect of the thalamus in the context of healthy aging. Using directed connectivity and weighted net causal outflow measures on resting-state fMRI data, we examine the age-related changes in both cortical and thalamocortical causal interactions within and between resting-state networks. The three of core neurocognitive networks DMN, SN, CEN networks are identified independently by carrying out ICA as well as spatially matching of hub regions with the important RSNs previously reported in the literature. Thereafter, multivariate GCA was performed to test for causality index between ROIs with and without the inclusion of left and right thalamus. There are two major findings, firstly, we observe that within network causal connections become progressively weaker with age, however, between network causal connections are getting stronger with age among core neurocognitive networks, primarily a reflection of within and between network resting-state functional connectivity. Secondly, significant modifications were found in causal connections and net causal outflows in the presence of thalamus. Finally, we found that the thalamus plays a crucial role as an exogenous drive in the reorganization of within network causal outflow, while Salience network plays a critical role in mediating between network causal outflow with age among cortical networks. Our findings with the weighted causal outflow measures strengthen the hypothesis that balancing within and between network connectivity is perhaps critical for the preservation of cognitive functions with aging.