title: Serotonergic modulation of intrinsic functional connectivity.
abstract: Serotonin functions as an essential neuromodulator that serves a multitude of roles, most prominently balancing mood. Serotonergic challenge has been observed to reduce intrinsic functional connectivity in brain regions implicated in mood regulation. However, the full scope of serotonergic action on functional connectivity in the human brain has not been explored. Here, we show evidence that a single dose of a serotonin reuptake inhibitor dramatically alters functional connectivity throughout the whole brain in healthy subjects (n = 22). Our network-centrality analysis reveals a widespread decrease in connectivity in most cortical and subcortical areas. In the cerebellum and thalamus, however, we find localized increases. These rapid and brain-encompassing connectivity changes linked to acute serotonin transporter blockade suggest a key role for the serotonin transporter in the modulation of the functional macroscale connectome.
authors.affiliation: Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany; Department of Electrical and Computer Engineering, Clinical Imaging Research Centre & Singapore Insitute for Neurotechnology, National University of Singapore, 117583 Singapore, Singapore.
authors.forename: Alexander
authors.initials: A
authors.lastname: Schaefer
authors.affiliation: Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany.
authors.forename: Inga
authors.initials: I
authors.lastname: Burmann
authors.affiliation: Division of Clinical Pharmacology, Rudolf-Boehm-Institute of Pharmacology and Toxicology, University of Leipzig, 04107 Leipzig, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Regenthal
authors.affiliation: Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany; Clinic of Cognitive Neurology, University Hospital Leipzig, 04103 Leipzig, Germany; Leipzig Research Center for Civilization Diseases, University of Leipzig, 04103 Leipzig, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Arélin
authors.affiliation: Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Barth
authors.affiliation: Nuclear Magnetic Resonance Unit, Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany.
authors.forename: André
authors.initials: A
authors.lastname: Pampel
authors.affiliation: Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany; Clinic of Cognitive Neurology, University Hospital Leipzig, 04103 Leipzig, Germany; Leipzig Research Center for Civilization Diseases, University of Leipzig, 04103 Leipzig, Germany; Integrated Research and Treatment Center Adiposity Diseases, University of Leipzig, 04103 Leipzig, Germany; Berlin School of Mind and Brain, Mind and Brain Institute, Charité and Humboldt University, 10099 Berlin, Germany.
authors.forename: Arno
authors.initials: A
authors.lastname: Villringer
authors.affiliation: Berlin School of Mind and Brain, Mind and Brain Institute, Charité and Humboldt University, 10099 Berlin, Germany; Max Planck Research Group for Neuroanatomy & Connectivity, Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Margulies
authors.affiliation: Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany; Clinic of Cognitive Neurology, University Hospital Leipzig, 04103 Leipzig, Germany; Berlin School of Mind and Brain, Mind and Brain Institute, Charité and Humboldt University, 10099 Berlin, Germany. Electronic address: sacher@cbs.mpg.de.
authors.forename: Julia
authors.initials: J
authors.lastname: Sacher
mesh_terms: D000328:Adult; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D015283:Citalopram / Q000494:pharmacology*; D063132:Connectome; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D011897:Random Allocation; D012701:Serotonin / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D015283:Citalopram; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors