Structure-function tethering of human locus coeruleus connectivity reveals a noradrenergic cortical hierarchy

The locus coeruleus (LC) is the primary source of cerebral norepinephrine and plays a broad role in cognition. Here, we show the macroscale organization of human LC connectivity using 7 T diffusion and resting-state functional magnetic resonance imaging (MRI). Structural and functional connectivity exhibit a dominant rostral-caudal gradient, with structure-function tethering lowest in the intermediate LC and increasing toward its rostral and caudal portions. In the neocortex, this pattern is expressed as steeply increasing tethering from the central sulcus toward anterior and posterior regions. Allen Mouse Brain Connectivity Atlas tracing further reveals preferential LC projections to somatomotor cortex. The cortical expression of LC structure-function tethering exhibits a network-level hierarchy and aligns with a behavioral axis. Additionally, this cortical expression shows significant spatial covariance with norepinephrine transporter concentration, fiber length, and gray matter volume. Together, these findings provide MRI-based evidence for a hierarchical macroscale organization of human LC connectivity linking structural and functional architecture to cortical and behavioral variation.