title: Resting-State Functional Connectivity of the Locus Coeruleus in Humans: In Comparison with the Ventral Tegmental Area/Substantia Nigra Pars Compacta and the Effects of Age.
abstract: The locus coeruleus (LC) provides the primary noradrenergic inputs to the cerebral cortex. Despite numerous animal studies documenting the functions of the LC, research in humans is hampered by the small volume of this midbrain nucleus. Here, we took advantage of a probabilistic template, explored the cerebral functional connectivity of the LC with resting-state fMRI data of 250 healthy adults, and verified the findings by accounting for physiological noise in another data set. In addition, we contrasted connectivities of the LC and the ventral tegmental area/substantia nigra pars compacta. The results highlighted both shared and distinct connectivity of these 2 midbrain structures, as well as an opposite pattern of connectivity to bilateral amygdala, pulvinar, and right anterior insula. Additionally, LC connectivity to the fronto-parietal cortex and the cerebellum increases with age and connectivity to the visual cortex decreases with age. These findings may facilitate studies of the role of the LC in arousal, saliency responses and cognitive motor control and in the behavioral and cognitive manifestations during healthy and disordered aging. Although the first to demonstrate whole-brain LC connectivity, these findings need to be confirmed with high-resolution imaging.
authors.affiliation: Department of Psychiatry.
authors.forename: Sheng
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Psychiatry.
authors.forename: Sien
authors.initials: S
authors.lastname: Hu
authors.affiliation: Department of Internal Medicine, Yale University, New Haven, CT 06519, USA Medical Service, VA Connecticut Health Care System, West Haven, CT 06516, USA.
authors.forename: Herta H
authors.initials: HH
authors.lastname: Chao
authors.affiliation: Department of Psychiatry Department of Neurobiology Interdepartmental Neuroscience Program, Yale University, New Haven, CT 06520, USA Connecticut Mental Health Center, New Haven, CT 06519, USA.
authors.forename: Chiang-Shan R
authors.initials: CS
authors.lastname: Li
mesh_terms: D000293:Adolescent; D000328:Adult; D000375:Aging / Q000502:physiology*; D002531:Cerebellum / Q000000981:diagnostic imaging / Q000502:physiology; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000502:physiology; D063132:Connectome; D005260:Female; D006801:Humans; D008125:Locus Coeruleus / Q000000981:diagnostic imaging / Q000502:physiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000502:physiology; D065842:Pars Compacta / Q000000981:diagnostic imaging / Q000502:physiology*; D012044:Regression Analysis; D012146:Rest; D012727:Sex Characteristics; D017557:Ventral Tegmental Area / Q000000981:diagnostic imaging / Q000502:physiology*; D055815:Young Adult
keywords: VTA; dopamine; locus ceruleus; noradrenaline; resting-state functional connectivity