A thalamocorticostriatal dopamine network for psychostimulant-enhanced human cognitive flexibility

• Type of Material: Article
• Authors: Gregory R. Samanez-Larkin, Vanderbilt University; Joshua W. Buckholtz, Harvard University; Ronald L. Cowan, Vanderbilt University; Neil D. Woodward, Vanderbilt University; Rui Li, Vanderbilt University; M. Sib Ansari, Vanderbilt University; Catherine M. Arrington, Lehigh University; Ronald M. Baldwin, Molecular NeuroImaging; Clarence E. Smith, DXP Imaging; Michael T. Treadway, Emory University; Robert M. Kessler, Vanderbilt University; David H. Zald, Vanderbilt University
• Language: English
• Date: 2013-07-15
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 Society of Biological Psychiatry.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.biopsych.2012.10.032
• Title of Journal or Parent Work: Biological Psychiatry
• ISSN: 0006-3223
• Volume: 74
• Issue: 2
• Start Page: 99
• End Page: 105
• Grant/Funding Information: G.R.S.L. was supported by National Institute of Mental Health training grant T32-MH018921; National Institute on Aging post-doctoral NRSA F32-AG039131; and National Institute on Aging Pathway to Independence Award K99-AG042596 during data analysis and manuscript preparation.; This research was funded by National Institute on Drug Abuse grant R01-DA019670 to D.H.Z.; and was supported by CTSA AWARD No. UL1TR000445 from the National Center for Advancing Translational Science.
• Keywords: Nerve Net; Radionuclide Imaging; Thalamus; Cerebral Cortex; Humans; Adaptation, Psychological; Young Adult; Male; Corpus Striatum; Adult; Dopamine Antagonists; Benzamides; Dextroamphetamine; Pyrrolidines; Cognition; Dopamine; Adolescent; Female
• Research Categories: Biology, Neuroscience; Health Sciences, Mental Health; Psychology, Psychobiology

Abstract

Background: Everyday life demands continuous flexibility in thought and behavior. We examined whether individual differences in dopamine function are related to variability in the effects of amphetamine on one aspect of flexibility: task switching. Methods: Forty healthy human participants performed a task-switching paradigm following placebo and oral amphetamine administration. [18F]fallypride was used to measure D2/D3 baseline receptor availability and amphetamine-stimulated dopamine release. Results: The majority of the participants showed amphetamine-induced benefits through reductions in switch costs. However, such benefits were variable. Individuals with higher baseline thalamic and cortical receptor availability and striatal dopamine release showed greater reductions in switch costs following amphetamine than individuals with lower levels. The relationship between dopamine receptors and stimulant-enhanced flexibility was partially mediated by striatal dopamine release. Conclusions: These data indicate that the impact of the psychostimulant on cognitive flexibility is influenced by the status of dopamine within a thalamocorticostriatal network. Beyond demonstrating a link between this dopaminergic network and the enhancement in task switching, these neural measures accounted for unique variance in predicting the psychostimulant-induced cognitive enhancement. These results suggest that there may be measurable aspects of variability in the dopamine system that predispose certain individuals to benefit from and hence use psychostimulants for cognitive enhancement.