Age-related reorganization of locus coeruleus–cortical functional connectivity gradients

Abstract The locus coeruleus (LC) regulates attention, arousal, and adaptive behavior via widespread noradrenergic projections to cortex, yet its large-scale cortical organization and age-related vulnerability remain poorly understood. Using 7T MRI during naturalistic movie-viewing with neutral and negative emotional valence, study-specific LC delineation, and PET-derived receptor–transporter maps, we characterized LC–linked cortical organization in younger and older adults. Functional gradient analysis revealed two dominant axes: a stable primary gradient anchored by catecholaminergic receptor–transporter distributions, and a context-sensitive secondary gradient aligning with the visual–somatomotor (V–S) axis in neutral movie-viewing and the sensorimotor–association (S–A) axis in negative movie-viewing. During negative movie-viewing, older adults exhibited higher global and within-frontoparietal control network dispersion, indicating reduced functional differentiation, a pattern further associated with poorer emotional wellbeing. By revealing chemoarchitectural and context-sensitive LC–linked cortical organization, current work identifies mechanisms underlying age-related LC–linked cortical reorganization with consequences for mental health.