Dopamine depletion impairs frontostriatal functional connectivity during a set-shifting task
Open accessAbstract
We investigated the effect of transient dopamine depletion on functional connectivity during performance of the Wisconsin Card Sorting Task. Functional magnetic resonance imaging data were analyzed as a psychophysiological interaction, a statistical method used to identify functional connectivity during experimental manipulations. Nineteen healthy subjects were scanned, double blind, on 2 separate days: once after drinking an amino acid mixture deficient in the dopamine precursors tyrosine and phenylalanine, and once after drinking a nutritionally balanced mixture. In the balanced drink session, statistically significant connectivity between the frontal lobes and striatum was observed during set shifting, and the greater the prefrontostriatal connectivity, the faster the response time after a shift. Neither of these associations were observed after dopamine depletion. Moreover, dopamine depletion also reduced the degree of deactivation in areas normally suppressed during attention-demanding tasks, including the medial prefrontal cortex, posterior cingulate cortex, and hippocampus. Together, these results suggest that functional connectivity between the frontal lobes and basal ganglia during set shifting contributes to more efficient performance and that dopamine modulates this corticostriatal connectivity.
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In healthy controls, dopamine depletion impairs fronto-striatal functional connectivity during set-shifting, suggesting low dopamine may impair prefrontal control over the striatum in cognitive flexibility.
“In healthy controls, dopamine depletion impairs fronto-striatal functional connectivity during set-shifting, suggesting that low dopamine may impair the control that the prefrontal cortex exhibits over the striatum in governing cognitive flexibility (Nagano-Saito et al., 2008).”
From Imaging addiction: D2 receptors and dopamine signaling in the striatum as biomarkers for impulsivity (2014) · cites this paper as Nagano-Saito et al., 2008
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“RL OFC, CN, putamen, Insula, dlPFC, dACC, Thalamus 1,66,85,86,83,65,14,2,26 , vmPFC, lPFC 1,83,85,66,86,65,14,2 , Parietal Cortex 66,86,65,14 .”
- Authors
- Nagano-Saito, A., Leyton, M., Monchi, O., Goldberg, Y. K., He, Y., & Dagher, A.
- Affiliations
- Montreal Neurological Institute and Hospital (CA)
- Université de Montréal (CA)
- Corresponding author
- Dagher, Alain
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2008-04-02
- Volume
- 28
- Issue
- 14
- Pages
- 3697-3706
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6671089
- OpenAlex
- W2075278002
- Cited by
- 222
- References
- 72
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 6 · 2023: 5 · 2022: 10 · 2021: 8 · 2020: 9 · 2019: 14 · 2018: 14 · 2017: 10 · 2016: 10 · 2015: 17 · 2014: 17 · 2013: 20 · 2012: 22
- FWCI
- 8.81
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research (144079)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- dopamine depletion, set-shifting, Wisconsin Card Sorting Test, psychophysiological interaction, basal ganglia, medial prefrontal cortex, posterior cingulate cortex, hippocampus, neural deactivation, reaction time (psychology)
- MeSH terms
- Adult, Amino Acids, Attention, Brain Mapping, Corpus Striatum, Dopamine, Double-Blind Method, Female, Food, Formulated, Frontal Lobe, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Neural Pathways, Neuropsychological Tests, Oxygen, Psychophysics, Reaction Time
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