Cerebral blood flow predicts differential neurotransmitter activity

Application of metabolic magnetic resonance imaging measures such as cerebral blood flow in translational medicine is limited by the unknown link of observed alterations to specific neurophysiological processes. In particular, the sensitivity of cerebral blood flow to activity changes in specific ne...

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Bibliographic Details
Published in:Scientific reports 2018-03, Vol.8 (1), p.4074-11, Article 4074
Main Authors: Dukart, Juergen, Holiga, Štefan, Chatham, Christopher, Hawkins, Peter, Forsyth, Anna, McMillan, Rebecca, Myers, Jim, Lingford-Hughes, Anne R, Nutt, David J, Merlo-Pich, Emilio, Risterucci, Celine, Boak, Lauren, Umbricht, Daniel, Schobel, Scott, Liu, Thomas, Mehta, Mitul A, Zelaya, Fernando O, Williams, Steve C, Brown, Gregory, Paulus, Martin, Honey, Garry D, Muthukumaraswamy, Suresh, Hipp, Joerg, Bertolino, Alessandro, Sambataro, Fabio
Format: Article
Language:English
Subjects:
Adult
Anesthetics, Dissociative - administration & dosage
Antidepressive Agents, Second-Generation - administration & dosage
Antipsychotic Agents - administration & dosage
Blood flow
Blood pressure
Central Nervous System - diagnostic imaging
Central Nervous System Stimulants - administration & dosage
Cerebral blood flow
Cerebrovascular Circulation
Circulatory system
Dopamine receptors
Female
Glutamatergic transmission
Healthy Volunteers
Humans
Magnetic resonance imaging
Magnetic Resonance Imaging - methods
Male
Metabolism
Neuroimaging
Neurophysiological Monitoring - methods
Neurotransmitter Agents - metabolism
Receptor density
Young Adult
γ-Aminobutyric acid
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Summary:Application of metabolic magnetic resonance imaging measures such as cerebral blood flow in translational medicine is limited by the unknown link of observed alterations to specific neurophysiological processes. In particular, the sensitivity of cerebral blood flow to activity changes in specific neurotransmitter systems remains unclear. We address this question by probing cerebral blood flow in healthy volunteers using seven established drugs with known dopaminergic, serotonergic, glutamatergic and GABAergic mechanisms of action. We use a novel framework aimed at disentangling the observed effects to contribution from underlying neurotransmitter systems. We find for all evaluated compounds a reliable spatial link of respective cerebral blood flow changes with underlying neurotransmitter receptor densities corresponding to their primary mechanisms of action. The strength of these associations with receptor density is mediated by respective drug affinities. These findings suggest that cerebral blood flow is a sensitive brain-wide in-vivo assay of metabolic demands across a variety of neurotransmitter systems in humans.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-018-22444-0