title: Functional connectivity of the dorsal and median raphe nuclei at rest.
abstract: Serotonin (5-HT) is a neurotransmitter critically involved in a broad range of brain functions and implicated in the pathophysiology of neuropsychiatric illnesses including major depression, anxiety and sleep disorders. Despite being widely distributed throughout the brain, there is limited knowledge on the contribution of 5-HT to intrinsic brain activity. The dorsal raphe (DR) and median raphe (MR) nuclei are the source of most serotonergic neurons projecting throughout the brain and thus provide a compelling target for a seed-based probe of resting-state activity related to 5-HT. Here we implemented a novel multimodal neuroimaging approach for investigating resting-state functional connectivity (FC) between DR and MR and cortical, subcortical and cerebellar target areas. Using [(11)C]DASB positron emission tomography (PET) images of the brain serotonin transporter (5-HTT) combined with structural MRI from 49 healthy volunteers, we delineated DR and MR and performed a seed-based resting-state FC analysis. The DR and MR seeds produced largely similar FC maps: significant positive FC with brain regions involved in cognitive and emotion processing including anterior cingulate, amygdala, insula, hippocampus, thalamus, basal ganglia and cerebellum. Significant negative FC was observed within pre- and postcentral gyri for the DR but not for the MR seed. We observed a significant association between DR and MR FC and regional 5-HTT binding. Our results provide evidence for a resting-state network related to DR and MR and comprising regions receiving serotonergic innervation and centrally involved in 5-HT related behaviors including emotion, cognition and reward processing. These findings provide a novel advance in estimating resting-state FC related to 5-HT signaling, which can benefit our understanding of its role in behavior and neuropsychiatric illnesses.
authors.affiliation: Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging, Rigshospitalet, Copenhagen, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Vincent
authors.initials: V
authors.lastname: Beliveau
authors.affiliation: Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Claus
authors.initials: C
authors.lastname: Svarer
authors.affiliation: Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Vibe G
authors.initials: VG
authors.lastname: Frokjaer
authors.affiliation: Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging, Rigshospitalet, Copenhagen, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Gitte M
authors.initials: GM
authors.lastname: Knudsen
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
authors.forename: Douglas N
authors.initials: DN
authors.lastname: Greve
authors.affiliation: Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging, Rigshospitalet, Copenhagen, Denmark. Electronic address: patrick@nru.dk.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Fisher
mesh_terms: D000328:Adult; D001921:Brain / Q000033:anatomy & histology* / Q000000981:diagnostic imaging / Q000378:metabolism*; D002250:Carbon Radioisotopes; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D049268:Positron-Emission Tomography; D011903:Raphe Nuclei / Q000033:anatomy & histology* / Q000000981:diagnostic imaging / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D055815:Young Adult
chemical_list: D002250:Carbon Radioisotopes; D050486:Serotonin Plasma Membrane Transport Proteins
keywords: Dorsal raphe; Functional connectivity; Median raphe; Resting-state; Serotonin