Arousal modulates functional connectivity through structured and hemispherically asymmetric community architecture during wakefulness

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Abstract

Arousal fluctuates continuously during wakefulness, yet how these moment-to-moment variations shape large-scale functional connectivity (FC) remains unclear. Here, we combined 7T fMRI with concurrent pupillometry to quantify, for every functional connection, how time-varying FC covaries with spontaneous arousal in the awake human brain. Rather than exerting a uniform influence across the connectome, arousal organized FC into a low-dimensional set of seven connectivity communities, each defined by characteristic network compositions. These communities exhibited systematic but community-specific hemispheric asymmetries, revealing distinct patterns of lateralized arousal modulation. Notably, the ventral attention network showed a pronounced division of labor: left-hemisphere nodes participated flexibly across multiple arousal-sensitive communities, whereas right-hemisphere nodes formed a cohesive, segregated arousal-responsive module. Importantly, hemispheric asymmetry did not arise from global shifts in connectivity strength, but instead reflected structured spatial heterogeneity embedded within community architecture. This modular and asymmetric organization was highly preserved during naturalistic movie watching, indicating that arousal-related modulation of FC reflects intrinsic principles that generalize across awake cognitive contexts. Together, these findings demonstrate that moment-to-moment arousal fluctuations shape large-scale FC through structured, hemispherically asymmetric network organization during wakefulness.

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