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

Abstract

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 D 2 receptor availabilities with gray matter (GM) volumes in healthy humans. Positron emission tomography images of D 2 receptor (n = 34) and DAT (n = 17) captured with the specific radioligands [ 11 C]raclopride and [ 18 F]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, [ 11 C]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 [ 18 F]FE-PE2I BP ND and regional GM volumes. Our results suggest unique structural and functional corticostriatal associations involving D 2 receptor in healthy humans, which might be partially independent of the nigrostriatal pathway reflected by striatal DAT.

The relationship between glutamate, dopamine, and cortical gray matter: A simultaneous PET-MR study

“…The fact that gray matter volumes most strongly correlated with associative striatum dopamine receptor availability is consistent with the fact that corticostriatal tracts originating from the DLPFC primarily make contact with it [ 11 ]. Our findings are in agreement with previous work showing a positive correlation between associative striatum dopamine receptor availability and DLPFC gray matter volume [ 10 ]. Interestingly, the cluster identified in the earlier study was in the left DLPFC contrary to the right side in the present study.…”

“…Although the relationship between gray matter volumes and neurochemical systems has been previously studied [ 8 – 10 , 57 , 58 ], this multimodal study is to our knowledge the first investigating cortex volume in relation to the different aspects of dopaminergic (amphetamine-induced release and receptor availability) and glutamatergic function in the same group of subjects. The study in the same subjects of different components of the dopaminergic neurotransmission and the interaction with the glutamatergic system allows to show that the significant gray matter regions slightly overlap in the dorsolateral prefrontal region (Figs.…”

“…Previous studies in humans have used multimodal neuroimaging to investigate these circuits. Links have been highlighted between frontal gray matter volumes and dopamine, specifically an inverse relationship with dopamine synthesis capacity in people with psychosis [ 8 ], an inverse relationship with dopamine release and a direct one with D 2 receptor availability in healthy subjects [ 9 , 10 ]. However, these have been examined separately and the interaction with the glutamatergic system has not been previously investigated.…”