title: Functional connectivity and network analysis of midbrain and brainstem nuclei.
abstract: There is limited understanding of how monoamine-producing nuclei within midbrain and brainstem contribute to the formation and functional dynamics of brain networks across the human neocortex. We used resting state fMRI in 154 healthy participants to elucidate patterns of functional connectivity and network organization between cortical/subcortical regions and midbrain/brainstem nuclei. By means of univariate functional connectivity and graph-based analysis, we show that dopaminergic midbrain centers and the serotonergic dorsal raphe nucleus (DRN) are functionally integrated with the default mode network (DMN), whereas the remaining serotonergic raphe nuclei and the noradrenergic locus coeruleus are functionally integrated with the executive-control network (ECN). The majority of midbrain/brainstem nuclei show a high level of connectedness to other network modules classifying these nuclei as "connector" hubs. The additionally applied probabilistic independent component analysis (PICA) broadly corresponded with the results of the GT analysis, describing similar functionally-relevant cortical networks. Since monoaminergic neurotransmission is essential to neocortical function, and represents an important target for pharmacotherapy, our novel findings contribute to a comprehensive understanding of the functional organization of the human brain.
authors.affiliation: Psychiatric Brain & Body Research Group Jena, Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany. Electronic address: Karl-Juergen.Baer@med.uni-jena.de.
authors.forename: Karl-Jürgen
authors.initials: KJ
authors.lastname: Bär
authors.affiliation: Psychiatric Brain & Body Research Group Jena, Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany.
authors.forename: Feliberto
authors.initials: F
authors.lastname: de la Cruz
authors.affiliation: Psychiatric Brain & Body Research Group Jena, Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany.
authors.forename: Andy
authors.initials: A
authors.lastname: Schumann
authors.affiliation: Psychiatric Brain & Body Research Group Jena, Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Koehler
authors.affiliation: Psychiatric Brain & Body Research Group Jena, Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany.
authors.forename: Heinrich
authors.initials: H
authors.lastname: Sauer
authors.affiliation: Department of Psychiatry, Brighton and Sussex Medical School, BN1 9RR, UK.
authors.forename: Hugo
authors.initials: H
authors.lastname: Critchley
authors.affiliation: Psychiatric Brain & Body Research Group Jena, Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Wagner
mesh_terms: D000328:Adult; D002540:Cerebral Cortex / Q000502:physiology*; D063132:Connectome / Q000379:methods*; D059290:Dopaminergic Neurons / Q000502:physiology*; D065847:Dorsal Raphe Nucleus / Q000502:physiology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008636:Mesencephalon / Q000502:physiology*; D008875:Middle Aged; D009415:Nerve Net / Q000502:physiology*; D055815:Young Adult
keywords: Brainstem; Default mode network; Dopamine; Executive-control network; Graph theory; Independent component analysis; Midbrain; Noradrenalin; Serotonin