Age-related reconfiguration of locus coeruleus-cortical functional organization

The locus coeruleus (LC) regulates attention, arousal and adaptive behavior via widespread noradrenergic projections to cortex, yet its large-scale cortical organization and vulnerability to aging remain poorly understood. Using ultra-high-field 7T-MRI during naturalistic viewing of neutral and negative movie-clips, 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 of cortical organization: a stable primary gradient anchored by catecholaminergic receptor-transporter distributions, and a context-sensitive secondary gradient shifting from visual-somatomotor to sensorimotor-association axis during neutral to negative movie-viewing. Aging selectively altered LC-linked cortical organization during negative movie-viewing, with older adults exhibiting higher global and within-network frontoparietal control dispersion, indicating reduced functional differentiation, a pattern that predicted poorer emotional wellbeing. Together, by revealing chemoarchitectural and context-sensitive LC-cortical organization, this work identifies mechanisms underlying age-related cortical reorganization with consequences for mental health.