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

Hum Brain Mapp. 2021 Aug 15;42(12):4048-4058. doi: 10.1002/hbm.25538. Epub 2021 May 20.

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 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 [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 (BPND ) of these radioligands in the limbic, executive, and sensorimotor functional subregions of the striatum. Correlations between the radioligand BPND and regional GM volume were then examined by voxel-based morphometry. In line with the functional and anatomical connectivity, [11 C]raclopride BPND 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 BPND of this radioligand in the executive striatum and volumes of the prefrontal cortices and their adjacent areas as well as between the BPND 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 BPND 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.

Keywords: D2 receptor; MRI; PET; dopamine transporter; gray matter; striatum.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Dopamine Plasma Membrane Transport Proteins / metabolism*
  • Gray Matter / diagnostic imaging
  • Gray Matter / metabolism*
  • Gray Matter / pathology
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Neostriatum / diagnostic imaging
  • Neostriatum / metabolism*
  • Neostriatum / pathology
  • Positron-Emission Tomography
  • Prefrontal Cortex / diagnostic imaging
  • Prefrontal Cortex / metabolism*
  • Prefrontal Cortex / pathology
  • Radiopharmaceuticals / pharmacokinetics
  • Receptors, Dopamine D2 / metabolism*
  • Ventral Striatum / diagnostic imaging
  • Ventral Striatum / metabolism*
  • Ventral Striatum / pathology
  • Young Adult

Substances

  • DRD2 protein, human
  • Dopamine Plasma Membrane Transport Proteins
  • Radiopharmaceuticals
  • Receptors, Dopamine D2
  • SLC6A3 protein, human