title: Interactions between glutamate, dopamine, and the neuronal signature of response inhibition in the human striatum.
abstract: Response inhibition is a basic mechanism in cognitive control and dysfunctional in major psychiatric disorders. The neuronal mechanisms are in part driven by dopamine in the striatum. Animal data suggest a regulatory role of glutamate on the level of the striatum. We used a trimodal imaging procedure of the human striatum including F18-DOPA positron emission tomography, proton magnetic resonance spectroscopy, and functional magnetic resonance imaging of a stop signal task. We investigated dopamine synthesis capacity and glutamate concentration in vivo and their relation to functional properties of response inhibition. A mediation analysis revealed a significant positive association between dopamine synthesis capacity and inhibition-related neural activity in the caudate nucleus. This relationship was significantly mediated by striatal glutamate concentration. Furthermore, stop signal reaction time was inversely related to striatal activity during inhibition. The data show, for the first time in humans, an interaction between dopamine, glutamate, and the neural signature of response inhibition in the striatum. This finding stresses the importance of the dopamine-glutamate interaction for behavior and may facilitate the understanding of psychiatric disorders characterized by impaired response inhibition.
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany.|Department of Psychology, Humboldt Universität zu Berlin, Berlin, Germany.|Center for Adaptive Rationality, Max Planck Institute for Human Development, Berlin, Germany.
authors.forename: Robert C
authors.identifier: http://orcid.org/0000-0003-3286-6792
authors.initials: RC
authors.lastname: Lorenz
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany.|NeuroCure Excellence Cluster, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Gleich
authors.affiliation: Department of Nuclear Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Ralph
authors.initials: R
authors.lastname: Buchert
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany.|Max Planck Fellow Group 'Cognitive and Affective Control of Behavioral Adaptation', Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Schlagenhauf
authors.affiliation: Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany.|Department of Psychiatry and Psychotherapy, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Kühn
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany.|Department of Psychiatry and Psychotherapy, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Gallinat
mesh_terms: D000328:Adult; D000375:Aging / Q000502:physiology; D001931:Brain Mapping; D002421:Caudate Nucleus / Q000166:cytology / Q000000981:diagnostic imaging / Q000502:physiology; D003342:Corpus Striatum / Q000166:cytology / Q000000981:diagnostic imaging / Q000502:physiology*; D004298:Dopamine / Q000502:physiology*; D059290:Dopaminergic Neurons / Q000000981:diagnostic imaging / Q000502:physiology*; D005260:Female; D018698:Glutamic Acid / Q000502:physiology*; D006801:Humans; D007266:Inhibition, Psychological; D008279:Magnetic Resonance Imaging; D008297:Male; D009474:Neurons / Q000000981:diagnostic imaging / Q000502:physiology*; D049268:Positron-Emission Tomography; D011597:Psychomotor Performance / Q000502:physiology; D011930:Reaction Time / Q000502:physiology
chemical_list: D018698:Glutamic Acid; D004298:Dopamine
keywords: dopamine; functional magnetic resonance imaging; glutamate; magnetic resonance spectroscopy; multimodal imaging; positron emission tomography; response inhibition; striatum