The balance of local and distributed excitation shapes brain stability and reflects aging- and Alzheimer's disease-related alterations

Abstract

Human brain function emerges from the interplay between recurrent local activity and distributed inter-regional interactions. However, a biologically interpretable framework for quantifying this balance between the two factors at the whole-brain level remains lacking. Here, we extended an established biophysical model to quantify inter-regional excitation and newly introduced the recurrent ratio (R-ratio), a measure of the relative balance between intra- and inter-regional excitation. Dynamical analyses showed that an optimal R-ratio supports a trade-off between network stability and flexibility. Applying this framework to healthy aging and Alzheimer's disease revealed progressively increased R-ratios with advancing age and disease severity. In healthy individuals, higher R-ratios were associated with age-related alterations in brain morphology, molecular pathology, and cognitive function, whereas Alzheimer's disease was characterized by increased R-ratios accompanied by reduced dynamical persistence. Together, these findings establish the R-ratio as a biologically interpretable marker of whole-brain excitation balance and demonstrate its utility for linking biophysical mechanisms with large-scale brain dynamics, aging, and neurodegeneration.