Now or Later? An fMRI study of the effects of endogenous opioid blockade on a decision-making network.
Previously, we found that distinct brain areas predict individual selection bias in decisions between small immediate ("Now") and larger delayed rewards ("Later"). Furthermore, such selection bias can be manipulated by endogenous opioid blockade. To test whether blocking endogenous opioids with naltrexone (NTX) alters brain activity during decision-making in areas predicting individual bias, we compared fMRI BOLD signal correlated with Now versus Later decision-making after acute administration of NTX (50 mg) or placebo. We tested abstinent alcoholics and control subjects in a double-blind two-session design. We defined regions of interest (ROIs) centered on activation peaks predicting Now versus Later selection bias. NTX administration significantly increased BOLD signal during decision-making in the right lateral orbital gyrus ROI, an area where enhanced activity during decision-making predicts Later bias. Exploratory analyses identified additional loci where BOLD signal during decision-making was enhanced (left orbitofrontal cortex, left inferior temporal gyrus, and cerebellum) or reduced (right superior temporal pole) by NTX. Additional analyses identified sites, including the right lateral orbital gyrus, in which NTX effects on BOLD signal predicted NTX effects on selection bias. These data agree with opioid receptor expression in human frontal and temporal cortices, and suggest possible mechanisms of NTX's therapeutic effects.
Boettiger
Charlotte A
CA
Department of Psychology, Biomedical Research Imaging Center, University of North Carolina, Chapel Hill 27599-3270, United States. cab@unc.edu
Kelley
Elizabeth A
EA
Mitchell
Jennifer M
JM
D'Esposito
Mark
M
Fields
Howard L
HL
D000328:Adult; D000437:Alcoholism / Q000473:pathology / Q000523:psychology; D001931:Brain Mapping; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology; D002755:Choice Behavior / Q000187:drug effects; D004247:DNA / Q000235:genetics; D003657:Decision Making / Q000187:drug effects*; D004723:Endorphins / Q000037:antagonists & inhibitors* / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009271:Naltrexone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009415:Nerve Net / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology*; D010100:Oxygen / Q000097:blood; D020641:Polymorphism, Single Nucleotide; D011569:Psychiatric Status Rating Scales; D017450:Receptors, Opioid, mu / Q000235:genetics; D055815:Young Adult
D019208:Brain-Derived Neurotrophic Factor; D004723:Endorphins; D009292:Narcotic Antagonists; C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu; D009271:Naltrexone; D004247:DNA; D010100:Oxygen