ORIGINAL INVESTIGATION 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 direc-tion and extent of dopaminergic drug effects across individuals. Objectives We investigated whether individual differences in dopaminergic drug effects on human fronto-striatal func-tioning are associated with individual differences in white matter tracts. Methods The effects of the dopamine receptor agonist bro-mocriptine were assessed using functional magnetic reso-nance imaging in 22 healthy volunteers in a placebo-controlled, double-blind, within-subject design. Human psy-chopharmacology and functional neuroimaging were com-bined with functional connectivity analyses and structural connectivity analyses to establish a link between dopami-nergic 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 differ-ences 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 dopa-mine, cognition and the basal ganglia and have implications for the individual tailoring of dopaminergic drug therapy based on anatomical fronto-striatal connection strength