Relationship between regional gray matter volumes and dopamine D₂ receptor and transporter in living human brains

Although striatal dopamine neurotransmission is believed to be functionally linked to the formation of the corticostriatal network, there has been little evidence for this regulatory process in the human brain and its disruptions in neuropsychiatric disorders. Here, we aimed to investigate associations of striatal dopamine transporter (DAT) and D₂ receptor availabilities with gray matter (GM) volumes in healthy humans. Positron emission tomography images of D₂ receptor (n = 34) and DAT (n = 17) captured with the specific radioligands [¹¹C]raclopride and [¹⁸F]FE-PE2I, respectively, were acquired along with T1-weighted magnetic resonance imaging data in our previous studies, and were re-analyzed in this work. We quantified the binding potentials (BP_ND) of these radioligands in the limbic, executive, and sensorimotor functional subregions of the striatum. Correlations between the radioligand BP_ND and regional GM volume were then examined by voxel-based morphometry. In line with the functional and anatomical connectivity, [¹¹C]raclopride BP_ND in the limbic striatum was positively correlated with volumes of the uncal/parahippocampal gyrus and adjacent temporal areas. Similarly, we found positive correlations between the BP_ND of this radioligand in the executive striatum and volumes of the prefrontal cortices and their adjacent areas as well as between the BP_ND in the sensorimotor striatum and volumes of the somatosensory and supplementary motor areas. By contrast, no significant correlation was found between [¹⁸F]FE-PE2I BP_ND and regional GM volumes. Our results suggest unique structural and functional corticostriatal associations involving D₂ receptor in healthy humans, which might be partially independent of the nigrostriatal pathway reflected by striatal DAT.