Mesolimbic dopamine function is related to salience network connectivity: an integrative PET and MR study
File(s)MesolimbicDopamineFunction.pdf (2.15 MB)
Published version
Author(s)
Type
Journal Article
Abstract
Background
A wide range of neuropsychiatric disorders, from schizophrenia to drug addiction, involve abnormalities in both the mesolimbic dopamine system and the cortical salience network. Both systems play a key role in the detection of behaviorally relevant environmental stimuli. Although anatomical overlap exists, the functional relationship between these systems remains unknown. Preclinical research has suggested that the firing of mesolimbic dopamine neurons may activate nodes of the salience network, but in vivo human research is required given the species-specific nature of this network.
Methods
We employed positron emission tomography to measure both dopamine release capacity (using the D2/3 receptor ligand 11C-PHNO, n = 23) and dopamine synthesis capacity (using 18F-DOPA, n = 21) within the ventral striatum. Resting-state functional magnetic resonance imaging was also undertaken in the same individuals to investigate salience network functional connectivity. A graph theoretical approach was used to characterize the relationship between dopamine measures and network connectivity.
Results
Dopamine synthesis capacity was associated with greater salience network connectivity, and this relationship was particularly apparent for brain regions that act as information-processing hubs. In contrast, dopamine release capacity was associated with weaker salience network connectivity. There was no relationship between dopamine measures and visual and sensorimotor networks, indicating specificity of the findings.
Conclusions
Our findings demonstrate a close relationship between the salience network and mesolimbic dopamine system, and they are relevant to neuropsychiatric illnesses in which aberrant functioning of both systems has been observed.
A wide range of neuropsychiatric disorders, from schizophrenia to drug addiction, involve abnormalities in both the mesolimbic dopamine system and the cortical salience network. Both systems play a key role in the detection of behaviorally relevant environmental stimuli. Although anatomical overlap exists, the functional relationship between these systems remains unknown. Preclinical research has suggested that the firing of mesolimbic dopamine neurons may activate nodes of the salience network, but in vivo human research is required given the species-specific nature of this network.
Methods
We employed positron emission tomography to measure both dopamine release capacity (using the D2/3 receptor ligand 11C-PHNO, n = 23) and dopamine synthesis capacity (using 18F-DOPA, n = 21) within the ventral striatum. Resting-state functional magnetic resonance imaging was also undertaken in the same individuals to investigate salience network functional connectivity. A graph theoretical approach was used to characterize the relationship between dopamine measures and network connectivity.
Results
Dopamine synthesis capacity was associated with greater salience network connectivity, and this relationship was particularly apparent for brain regions that act as information-processing hubs. In contrast, dopamine release capacity was associated with weaker salience network connectivity. There was no relationship between dopamine measures and visual and sensorimotor networks, indicating specificity of the findings.
Conclusions
Our findings demonstrate a close relationship between the salience network and mesolimbic dopamine system, and they are relevant to neuropsychiatric illnesses in which aberrant functioning of both systems has been observed.
Date Issued
2019-03-01
Date Acceptance
2018-09-14
Citation
Biological Psychiatry, 2019, 85 (5), pp.368-378
ISSN
0006-3223
Publisher
Elsevier
Start Page
368
End Page
378
Journal / Book Title
Biological Psychiatry
Volume
85
Issue
5
Copyright Statement
© 2018 Society of Biological Psychiatry. This is an open access article under the
CC BY license (http://creativecommons.org/licenses/by/4.0/)
CC BY license (http://creativecommons.org/licenses/by/4.0/)
Sponsor
Engineering & Physical Science Research Council (EPSRC)
Grant Number
EP/N014529/1
Subjects
Science & Technology
Life Sciences & Biomedicine
Neurosciences
Psychiatry
Neurosciences & Neurology
F-18-DOPA
Functional connectivity
Graph theory
C-11-PHNO
Resting state
Striatum
DEFAULT-MODE NETWORK
CINGULATE CORTEX
BRAIN NETWORKS
RESTING BRAIN
HYPOTHESIS
PREDICTION
PSYCHOSIS
RELEASE
SYSTEM
IDENTIFICATION
(11)C-PHNO
(18)F-DOPA
Functional connectivity
Graph theory
Resting state
Striatum
06 Biological Sciences
17 Psychology and Cognitive Sciences
11 Medical and Health Sciences
Psychiatry
Publication Status
Published
Date Publish Online
2018-09-29