Abstract

The mesencephalic dopamine (DA) system is the main DA system related to affective and cognitive functions. The system consists of two different cell groups, A9 and A10, which originate from different regions of the midbrain. The striatum is the main input from the midbrain, and is functionally organized into associative, sensorimotor and limbic subdivisions. At present, there have been few studies investigating the associations of DA functions between striatal subdivisions and extrastriatal regions. The aim of this study was to investigate the relationship of DA D1 receptor (D1R) expression between striatal subdivisions and extrastriatal regions in humans using positron emission tomography (PET) with voxel-by-voxel whole brain analysis. The PET study was performed on 30 healthy subjects using [11C]SCH23390 to measure D1R expression. Parametric images of binding potentials (BP ND) were created using the simplified reference tissue model. Regions of interest were defined for striatal subdivisions. Multiple regression analysis was undertaken to determine extrastriatal regions that were associated with each striatal subdivision in BP ND using statistical parametric mapping 5. The BP ND values of associative, sensorimotor and limbic subdivisions were similarly correlated with those of multiple brain regions. Regarding the interrelationships among striatal subdivisions, mutual correlations were found among associative, sensorimotor and limbic subdivisions in BP ND as well. The relationships in BP ND between striatal subdivisions and extra-striatal regions suggest that differential striatal subdivisions and extrastriatal regions have a similar biological basis of D1R expression. Different DA projections from the midbrain did not explain the associations between striatal subdivisions and extrastriatal regions in D1R expression, and the DA-related neural networks among the midbrain, striatum and the other regions would contribute to a similar D1R expression pattern throughout the whole brain.

Highlights

  • The mesencephalic dopamine (DA) system is the main DA system, and it is related to affective and cognitive functions such as reward processing

  • The critical role of the DA system in cognitive functions has been suggested repeatedly, and abnormalities of the system have been implicated in the pathophysiology of several neuropsychiatric disorders such as schizophrenia [13,23] and Parkinson’s disease [10]

  • It has been suggested that cognitive functions such as executive function would be associated with the manner of interregional relationship in D1 receptor (D1R)

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Summary

Introduction

The mesencephalic dopamine (DA) system is the main DA system, and it is related to affective and cognitive functions such as reward processing. The system is roughly divided into different groups, A9 and A10, whose cells are located in different regions of the midbrain, the substantia nigra (SN) and the ventral tegmental area (VTA), respectively. These different projections have been reported in rats, monkeys and humans [1,2,3]. The striatum provides the main input from the midbrain This region is not uniform, and it is functionally divided into striatal subdivisions termed associative (AST), sensorimotor (SMST) and limbic (LST), which process information related to cognitive, sensorimotor, and emotional functions, respectively [4]. A10 would have direct projections to cortical regions as well

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