Anatomical connection strength predicts dopaminergic drug effects on fronto-striatal function

RATIONALE: The neurotransmitter dopamine plays a key role in cognitive functions that are associated with fronto-striatal circuitry and has been implicated in many neuropsychiatric disorders. However, there is a large variability in the direction and extent of dopaminergic drug effects across individuals. OBJECTIVES: We investigated whether individual differences in dopaminergic drug effects on human fronto-striatal functioning are associated with individual differences in white matter tracts. METHODS: The effects of the dopamine receptor agonist bromocriptine were assessed using functional magnetic resonance imaging in 22 healthy volunteers in a placebo-controlled, double-blind, within-subject design. Human psychopharmacology and functional neuroimaging were combined with functional connectivity analyses and structural connectivity analyses to establish a link between dopaminergic drug effects on fronto-striatal function and fronto-striatal anatomy. RESULTS: We demonstrate that bromocriptine alters functional signals associated with attention switching in the basal ganglia. Crucially, individual differences in the drug’s effect on these signals could be predicted from individual differences in fronto-striato-thalamic white matter tracts, as indexed by diffusion tensor imaging. Anatomical fronto-striatal connectivity also predicted drug effects on switch-related functional connectivity between the basal ganglia and the prefrontal cortex. CONCLUSIONS: These data reinforce the link between dopamine, cognition and the basal ganglia and have implications for the individual tailoring of dopaminergic drug therapy based on anatomical fronto-striatal connection strength. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00213-013-3000-5) contains supplementary material, which is available to authorized users.