Connectivity-Based Functional Analysis of Dopamine Release in the Striatum Using Diffusion-Weighted MRI and Positron Emission Tomography

Abstract

The striatum acts in conjunction with the cortex to control and execute functions that are impaired by abnormal dopamine neurotransmission in disorders such as Parkinson's and schizophrenia. To date, in vivo quantification of striatal dopamine has been restricted to structure-based striatal subdivisions. Here, we present a multimodal imaging approach that quantifies the endogenous dopamine release following the administration of d-amphetamine in the functional subdivisions of the striatum of healthy humans with [(11)C]PHNO and [(11)C]Raclopride positron emission tomography ligands. Using connectivity-based (CB) parcellation, we subdivided the striatum into functional subregions based on striato-cortical anatomical connectivity information derived from diffusion magnetic resonance imaging (MRI) and probabilistic tractography. Our parcellation showed that the functional organization of the striatum was spatially coherent across individuals, congruent with primate data and previous diffusion MRI studies, with distinctive and overlapping networks. d-amphetamine induced the highest dopamine release in the limbic followed by the sensory, motor, and executive areas. The data suggest that the relative regional proportions of D2-like receptors are unlikely to be responsible for this regional dopamine release pattern. Notably, the homogeneity of dopamine release was significantly higher within the CB functional subdivisions in comparison with the structural subdivisions. These results support an association between local levels of dopamine release and cortical connectivity fingerprints.

Long-Term Test–Retest Reliability of Striatal and Extrastriatal Dopamine D2/3 Receptor Binding: Study with [11C]Raclopride and High-Resolution PET

“…[12][13][14] Moreover, a recent study using diffusion-weighted magnetic resonance imaging and PET found that connectivity-based subdivision of human striatum improved the evaluation of regional differences in DA transmission, supporting an association between striatal DA release and cortical connectivity. 35 36,37 In the current study, cortical VAR and ICC values were good to moderate, ranging from 6.1%, 0.79 (temporal cortex) to 13.1%, 0.67 (superior frontal gyrus). This is clearly superior to previous results by Stokes et al 11 and comparable to test-retest parameters obtained with high-affinity ligands.…”

Regional specialization within the human striatum for diverse psychological functions

“…Nevertheless, this divergence also suggests that even though the results of our cluster analysis were highly robust, different striatal zones may have emerged had we performed it on a measure other than coactivation. Interestingly (59), found that patterns of striatal dopamine release did not converge with structural subdivisions, but with corticostriatal activation patterns, which were also the basis of our parcellation (SI Appendix, Fig. S12 shows results based on the NeuroSynth database).…”

Amphetamine-Induced Dopamine Release and Neurocognitive Function in Treatment-Naive Adults with ADHD

“…These ROIs are based on the topography of functionally distinct cortico-striatal-thalamo-cortical circuits in non-human primates (Haber, 2010). According to a recent delineation of striatal subregions based on corticostriatal connectivity in humans (Tziortzi et al, 2013), our peak voxels of DA release in the AST map onto loci connected with prefrontal executive cortical areas; peak voxels in SMST map onto loci connected with executive and premoter regions. Thus, it is plausible that the group differences in DA release in these striatal regions are linked with executive and motor control, but not with motivation and reward.…”