title: 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.
authors.affiliation: FMRIB Centre, Nuffield Department of Clinical Neurosciences.
authors.forename: Andri C
authors.initials: AC
authors.lastname: Tziortzi
authors.forename: Suzanne N
authors.initials: SN
authors.lastname: Haber
authors.forename: Graham E
authors.initials: GE
authors.lastname: Searle
authors.forename: Charalampos
authors.initials: C
authors.lastname: Tsoumpas
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Long
authors.forename: Paul
authors.initials: P
authors.lastname: Shotbolt
authors.forename: Gwenaelle
authors.initials: G
authors.lastname: Douaud
authors.forename: Saad
authors.initials: S
authors.lastname: Jbabdi
authors.forename: Timothy E J
authors.initials: TE
authors.lastname: Behrens
authors.forename: Eugenii A
authors.initials: EA
authors.lastname: Rabiner
authors.forename: Mark
authors.initials: M
authors.lastname: Jenkinson
authors.forename: Roger N
authors.initials: RN
authors.lastname: Gunn
mesh_terms: D000328:Adult; D001931:Brain Mapping; D003342:Corpus Striatum / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism*; D056324:Diffusion Tensor Imaging; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology; D056344:Executive Function / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism; D049268:Positron-Emission Tomography; D011336:Probability; D020891:Raclopride / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D018492:Dopamine Antagonists; D020891:Raclopride; D004298:Dopamine
keywords: diffusion-weighted image; dopamine receptors; positron emission tomography; probabilistic tractography; striatum