Mesolimbic Dopamine Function is Related to Salience Network Connectivity: An Integrative PET and MR Study

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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 behaviourally
relevant environmental stimuli. Although anatomical overlap exists, the functional
relationship between these systems remains unknown. Preclinical research has
suggested 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.
We employed positron emission tomography to measure both dopamine release
capacity (using [11C]-(+)-PHNO, n =23), and dopamine synthesis capacity (using 3,4-
dihydroxy-6-[18F]fluoro-L-phenylalanine, n =21) within the ventral striatum. Restingstate
functional magnetic resonance imaging was also undertaken in the same
individuals to investigate salience network functional connectivity. A graph theoretical
approach was used to characterise the relationship between dopamine measures and
network connectivity.
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
Our findings demonstrate a close relationship between the salience network and
mesolimbic dopamine system, and are relevant to neuropsychiatric illnesses in which
aberrant functioning of both systems has been observed.
Original languageEnglish
JournalBiological psychiatry
Publication statusAccepted/In press - 18 Sept 2018


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