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

Abstract

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. Methods: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. 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 characterise 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 are relevant to neuropsychiatric illnesses in which aberrant functioning of both systems has been observed.