Local homeostasis preserves global neural dynamics compensating for structural loss during human lifespan aging

Area of Science:

• Neuroscience
• Computational Neuroscience
• Biophysics

Background:

• The aging brain experiences structural decline and altered neurotransmitter levels, impacting functional markers.
• Coordination in the resting-state human brain shows preservation along aging trajectories, but the underlying mechanisms are unclear.

Purpose of the Study:

• To identify computational mechanisms involving neurotransmitters that preserve functional integration in the aging brain despite structural decline.
• To investigate the roles of gamma-aminobutyric acid (GABA) and glutamate in maintaining brain network dynamics across the lifespan.

Main Methods:

• Utilized multiscale, biophysically grounded modeling constrained by the human brain's anatomical connectome.
• Treated neurotransmitter concentrations as adjustable parameters to maintain regional homeostasis and optimal working points.
• Employed graph-theoretic metrics for validation on multiple datasets.

Main Results:

• Identified invariant GABA and reduced glutamate concentrations as key computational mechanisms preserving functional integration.
• Demonstrated that these neurotransmitter changes maintain critical firing rates and mimic age-associated functional connectivity patterns.
• Validated findings across three distinct empirical datasets.

Conclusions:

• The study provides an operational framework integrating macroscopic brain network dynamics and molecular-scale neurotransmitter concentrations.
• Invariant GABA and reduced glutamate are identified as crucial for explaining age-related functional connectivity variations.
• The findings offer insights into age-associated neural disorders and the neurocomputational principles of brain aging.