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.
This is the first study to investigate the relationship between regional gray matter volumes and availabilities of both dopamine D2 receptor and transporter in the striatum of healthy adults, by using our previous magnetic resonance imaging and positron emission tomography datasets. We have demonstrated positive correlations between dopamine D2/3 receptor radioligand BP ND in the functional subregions of the striatum and the gray matter (GM) volumes of regions that could be functionally and anatomically connected to each of these striatal subdomains. Meanwhile, no marked correlations were observed between dopamine transporter radioligand BP ND and regional GM volumes.