Functional connectivity and network analysis of midbrain and brainstem nuclei

• Published in: NeuroImage (Orlando, Fla.) Fla.), 2016-07, Vol.134, p.53-63
• Main Authors: Bär, Karl-Jürgen, de la Cruz, Feliberto, Schumann, Andy, Koehler, Stefanie, Sauer, Heinrich, Critchley, Hugo, Wagner, Gerd
• Format: Article
• Language: English
• Subjects: Adult; Brain; Brain architecture; Brain mapping; Brain stem; Brainstem; Cerebral Cortex - physiology; Connectome - methods; Default mode network; Dopamine; Dopamine receptors; Dopaminergic Neurons - physiology; Dorsal raphe nucleus; Dorsal Raphe Nucleus - physiology; Executive-control network; Female; Functional magnetic resonance imaging; Functional morphology; Graph theory; Humans; Independent component analysis; Locus coeruleus; Magnetic Resonance Imaging - methods; Male; Mesencephalon; Mesencephalon - physiology; Midbrain; Middle Aged; Neocortex; Nerve Net - physiology; Neural networks; Neurotransmission; Noradrenalin; Norepinephrine; Raphe nuclei; Serotonin; Young Adult
• ISSN: 1053-8119; 1095-9572
• DOI: 10.1016/j.neuroimage.2016.03.071

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. •Dopaminergic nuclei and the dorsal raphe nucleus are integrated with the default mode network.•Lower raphe nuclei/locus coeruleus show connectivity to executive-control network.•All midbrain/brainstem nuclei except nucleus raphes pontis show a high level of connectedness to other network.