TY - JOUR
T1 - Dopamine modulates the functional organization of the orbitofrontal cortex
AU - Kahnt, Thorsten
AU - Tobler, Philippe N.
N1 - Funding Information:
Research reported in this publication was supported by the National Institute on Deafness and Other Communication Disorders of the National Institutes of Health (NIH) under Award R01-DC-015426 (to T.K.), and by Swiss National Science Foundation Grants PP00P1_128574, PP00P1_150739, CRSII3_141965, and 00014_165884 (to P.N.T.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. We thank H. Haker, T. Baumgartner, S. Weber, and M. W?lti for assistance in subject recruitment and data acquisition; and M. Mesulam, L.J. Chang, and J.D. Howard for helpful discussions, comments, and suggestions.
PY - 2017/2/8
Y1 - 2017/2/8
N2 - Neuromodulators such as dopamine can alter the intrinsic firing properties of neurons and may thereby change the configuration of larger functional circuits. The primate orbitofrontal cortex (OFC) receives dopaminergic input from midbrain nuclei, but the role of dopamine in the OFC is still unclear. Here we tested the idea that dopaminergic activity changes the pattern of connectivity between the OFC and the rest of the brain and thereby reconfigures functional networks in the OFC. To this end, we combined double-blind, placebo-controlled pharmacology [D2 receptor (D2R) antagonist amisulpride] in humans with resting-state functional magnetic resonance imaging and clustering methods. In the placebo group, we replicated previously observed parcellations of the OFC into two and six subregions based on connectivity patterns with the rest of the brain. Most importantly, while the twofold clustering did not differ significantly between groups, blocking D2Rs significantly changed the composition of the sixfold parcellation, suggesting a dopamine-dependent reconfiguration of functional OFC subregions. Moreover, multivariate decoding analyses revealed that amisulpride changed the whole-brain connectivity patterns of individual OFC subregions. In particular, D2R blockade shifted the balance of OFC connectivity from associative areas in the temporal and parietal lobe toward functional connectivity with the frontal cortex. In summary, our results suggest that dopamine alters the composition of functional OFC circuits, possibly indicating a broader role for neuromodulators in the dynamic reconfiguration of functional brain networks.
AB - Neuromodulators such as dopamine can alter the intrinsic firing properties of neurons and may thereby change the configuration of larger functional circuits. The primate orbitofrontal cortex (OFC) receives dopaminergic input from midbrain nuclei, but the role of dopamine in the OFC is still unclear. Here we tested the idea that dopaminergic activity changes the pattern of connectivity between the OFC and the rest of the brain and thereby reconfigures functional networks in the OFC. To this end, we combined double-blind, placebo-controlled pharmacology [D2 receptor (D2R) antagonist amisulpride] in humans with resting-state functional magnetic resonance imaging and clustering methods. In the placebo group, we replicated previously observed parcellations of the OFC into two and six subregions based on connectivity patterns with the rest of the brain. Most importantly, while the twofold clustering did not differ significantly between groups, blocking D2Rs significantly changed the composition of the sixfold parcellation, suggesting a dopamine-dependent reconfiguration of functional OFC subregions. Moreover, multivariate decoding analyses revealed that amisulpride changed the whole-brain connectivity patterns of individual OFC subregions. In particular, D2R blockade shifted the balance of OFC connectivity from associative areas in the temporal and parietal lobe toward functional connectivity with the frontal cortex. In summary, our results suggest that dopamine alters the composition of functional OFC circuits, possibly indicating a broader role for neuromodulators in the dynamic reconfiguration of functional brain networks.
KW - Connectivity
KW - Dopamine
KW - FMRI
KW - Orbitofrontal cortex
KW - Parcellation
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U2 - 10.1523/JNEUROSCI.2827-16.2016
DO - 10.1523/JNEUROSCI.2827-16.2016
M3 - Article
C2 - 28069917
AN - SCOPUS:85011964938
VL - 37
SP - 1493
EP - 1504
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 6
ER -