Imaging human reward processing with positron emission tomography and functional magnetic resonance imaging
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Functional neuroimaging (fMRI) studies show activation in mesolimbic circuitry in tasks involving reward processing, like the Monetary Incentive Delay Task (MIDT). In voltammetry studies in animals, mesolimbic dopamine release is associated with reward salience. This study examined the relationship between fMRI activation and magnitude of dopamine release measured with Positron emission tomography study (PET) in the same subjects using MIDT in both modalities to test if fMRI activation is related to dopamine release. Eighteen healthy subjects were scanned with [11 C]raclopride PET at baseline and after MIDT. Binding potential (BPND) was derived by equilibrium analysis in striatal subregions and percent change across conditions (∆BPND) was measured. Blood oxygen level dependence (BOLD) signal changes with MIDT were measured during fMRI using voxelwise analysis and ROI analysis and correlated with ∆BPND. ∆BPND was not significant in the ventral striatum (VST) but reached significance in the posterior caudate. The fMRI BOLD activation was highest in VST. No significant associations between ∆BPND and change in fMRI BOLD were observed with VST using ROI analysis. Voxelwise analysis showed positive correlation between BOLD activation in anticipation of the highest reward and ∆BPND in VST and precommissural putamen. Our study indicates that endogenous dopamine release in VST is of small magnitude and is related to BOLD signal change during performance of the MIDT in only a few voxels when rewarding and nonrewarding conditions are interspersed. The lack of correlation at the ROI level may be due to the small magnitude of release or to the particular dependence of BOLD on glutamatergic signaling.
KeywordsHuman reward processing Dopamine MIDT PET fMRI
We would like to thank Mr. Ben Gunter for technical support with the fMRI arm of the study. This research was carried out at New York State Psychiatric Institute/Columbia University Medical Center under a subcontract from the Center for Translational Neuroscience of Alcoholism at Yale University, supported by grant number P50AA-012870-09 from the National Institute on Alcohol Abuse and Alcoholism. The funding agency had no role in the design and conduct of the study; in the collection, analysis, and interpretation of the data; or in the preparation, review, or approval of the manuscript.
Financial disclosures: M. Slifstein: consultant: Amgen, GlaxoSmithKline; research support: Pierre Fabre, Inc.; J.H. Krystal reports the following: consultant: Aisling Capital, LLC, AstraZeneca Pharmaceuticals, Brintnall & Nicolini, Inc., Easton Associates, Gilead Sciences, Inc., GlaxoSmithKline, Janssen Pharmaceuticals, Lundbeck Research USA, Medivation, Inc., Merz Pharmaceuticals, MK Medical Communications, F. Hoffmann-La Roche Ltd., SK Holdings Co., Ltd., Takeda Industries, Teva Pharmaceutical Industries, Ltd.; scientific advisory board: Abbott Laboratories, Bristol-Myers Squibb, Eisai, Inc., Eli Lilly and Co., Lohocla Research Corporation, Naurex, Inc., Pfizer Pharmaceuticals Exercisable Warrant Options (value less than $500): Tetragenex Pharmaceuticals; research/study drug support: Janssen Research Foundation (to the Department of Veterans Affairs); Board of Directors: Coalition for Translational Research in Alcohol and Substance Use Disorders, American College of Neuropsychopharmacology (President elect); Editor: Biological Psychiatry; inventions: 1) Seibyl JP, Krystal JH, Charney DS. Dopamine and noradrenergic reuptake inhibitors in treatment of schizophrenia. Patent #: 5,447,948. September 5, 1995; 2) coinventor with Dr. Gerard Sanacora on a filed patent application by Yale University related to targeting the glutamatergic system for the treatment of neuropsychiatric disorders (PCTWO06108055A1); and 3) Intranasal Administration of Ketamine to Treat Depression (pending). A. Abi-Dargham: Bristol-Myers Squibb-Otsuka (consultant and speaker), Bohringer-Engelheim, Lundbeck, Sepracor, Merck (consultant), GlaxoSmithKline (research grant). All other authors reported no biomedical financial interests or potential conflicts of interest.
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