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

Area of Science:

• Neuroscience
• Computational Biology
• Gerontology

Background:

• Cognitive decline during aging is linked to changes in brain networks.
• The precise mechanisms connecting structural and functional brain changes to cognitive aging remain unclear.

Purpose of the Study:

• To establish a causal link between structural connectivity, functional brain architecture, and cognitive decline in aging.
• To model the effects of white matter degradation on brain network dynamics and cognitive function.

Main Methods:

• Developed a brain network modeling framework to simulate interhemispheric structural connectivity degradation.
• Utilized in-silico experiments to observe functional dedifferentiation and changes in brain dynamics.
• Employed a deep-learning Bayesian approach to validate the causal hypothesis.

Main Results:

• Successfully reproduced functional dedifferentiation in aging models through simulated white matter degradation.
• Observed increased global modulation of brain dynamics by structural connectivity with age.
• Found a steeper increase in modulation in older adults with poorer cognitive performance.

Conclusions:

• Provided the first mechanistic demonstration of how functional dedifferentiation during aging contributes to cognitive decline.
• Highlighted the critical role of structural connectivity in maintaining cognitive function throughout the aging process.