4.7 Article

The virtual aging brain: Causal inference supports interhemispheric dedifferentiation in healthy aging

Journal

NEUROIMAGE
Volume 283, Issue -, Pages -

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.neuroimage.2023.120403

Keywords

White-matter degradation; Functional dedifferentiation; Functional connectivity; Structural connectivity; Aging; Cognitive decline

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The study used a brain network modeling framework to infer the causal link between structural connectivity and functional architecture and demonstrated that global modulation of brain dynamics increases with age, particularly in older adults with poor cognitive performance. The researchers validated their hypothesis using a deep-learning Bayesian approach, providing mechanistic evidence of dedifferentiation leading to cognitive decline during aging.
The mechanisms of cognitive decline and its variability during healthy aging are not fully understood, but have been associated with reorganization of white matter tracts and functional brain networks. Here, we built a brain network modeling framework to infer the causal link between structural connectivity and functional architecture and the consequent cognitive decline in aging. By applying in-silico interhemispheric degradation of structural connectivity, we reproduced the process of functional dedifferentiation during aging. Thereby, we found the global modulation of brain dynamics by structural connectivity to increase with age, which was steeper in older adults with poor cognitive performance. We validated our causal hypothesis via a deep-learning Bayesian approach. Our results might be the first mechanistic demonstration of dedifferentiation during aging leading to cognitive decline.

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