title: Dopamine precursor depletion impairs structure and efficiency of resting state brain functional networks.
abstract: Spatial patterns of functional connectivity derived from resting brain activity may be used to elucidate the topological properties of brain networks. Such networks are amenable to study using graph theory, which shows that they possess small world properties and can be used to differentiate healthy subjects and patient populations. Of particular interest is the possibility that some of these differences are related to alterations in the dopamine system. To investigate the role of dopamine in the topological organization of brain networks at rest, we tested the effects of reducing dopamine synthesis in 13 healthy subjects undergoing functional magnetic resonance imaging. All subjects were scanned twice, in a resting state, following ingestion of one of two amino acid drinks in a randomized, double-blind manner. One drink was a nutritionally balanced amino acid mixture, and the other was tyrosine and phenylalanine deficient. Functional connectivity between 90 cortical and subcortical regions was estimated for each individual subject under each dopaminergic condition. The lowered dopamine state caused the following network changes: reduced global and local efficiency of the whole brain network, reduced regional efficiency in limbic areas, reduced modularity of brain networks, and greater connection between the normally anti-correlated task-positive and default-mode networks. We conclude that dopamine plays a role in maintaining the efficient small-world properties and high modularity of functional brain networks, and in segregating the task-positive and default-mode networks. This article is part of the Special Issue Section entitled 'Neuroimaging in Neuropharmacology'.
authors.affiliation: Montreal Neurological Institute, McGill University, Montreal, Canada.
authors.forename: Felix
authors.initials: F
authors.lastname: Carbonell
authors.affiliation: Montreal Neurological Institute, McGill University, Montreal, Canada.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Nagano-Saito
authors.affiliation: Department of Psychiatry, McGill University, Montreal, Canada.
authors.forename: Marco
authors.initials: M
authors.lastname: Leyton
authors.affiliation: Département de Physiologie, Université de Montréal, Montréal, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Cisek
authors.affiliation: Department of Psychiatry, McGill University, Montreal, Canada.
authors.forename: Chawki
authors.initials: C
authors.lastname: Benkelfat
authors.affiliation: State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: He
authors.affiliation: Montreal Neurological Institute, McGill University, Montreal, Canada. Electronic address: alain.dagher@mcgill.ca.
authors.forename: Alain
authors.initials: A
authors.lastname: Dagher
mesh_terms: D000328:Adult; D000465:Algorithms; D000596:Amino Acids / Q000008:administration & dosage* / Q000097:blood; D001921:Brain / Q000502:physiology*; D001931:Brain Mapping / Q000379:methods; D004298:Dopamine / Q000378:metabolism*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008959:Models, Neurological; D009434:Neural Pathways / Q000502:physiology; D010649:Phenylalanine / Q000097:blood / Q000172:deficiency*; D012146:Rest; D012815:Signal Processing, Computer-Assisted; D014443:Tyrosine / Q000097:blood / Q000172:deficiency*; D055815:Young Adult
chemical_list: D000596:Amino Acids; D014443:Tyrosine; D010649:Phenylalanine; D004298:Dopamine
keywords: Default mode network; Dopamine; Efficiency; Functional connectivity; Modularity; Resting state; Small world network; fMRI