Abstract

Increasing evidence shows that the midbrain dopaminergic system is involved in various functions. However, details of the role of the midbrain dopaminergic system in these functions are still to be determined in humans. Considering that the ventral tegmental area (VTA) and substantia nigra (SN) in the midbrain are the primary dopamine producers, creating reliable anatomical templates of the VTA and SN through neuroimaging studies would be useful for achieving a detailed understanding of this dopaminergic system. Although VTA and SN anatomical templates have been created, no specific templates exist for the Asian population. Thus, we conducted anatomical and resting-state functional magnetic resonance imaging (rs-fMRI) studies to create VTA and SN templates for the Asian population. First, a neuromelanin-sensitive MRI technique was used to visualize the VTA and SN, and then individual hand-drawn VTA and SN regions of interests (ROIs) were traced on a small sample of neuromelanin-sensitive MRIs (dataset 1). Second, individual hand-drawn VTA and SN ROIs were normalized to create normalized VTA and SN templates for the Asian population. Third, a seed-based functional connectivity analysis was performed on rs-fMRI data using hand-drawn ROIs to calculate neural networks of VTA and SN in dataset 1. Fourth, a seed-based functional connectivity analysis was performed using VTA and SN seeds that were created based on normalized templates from dataset 1. Subsequently, a seed-based functional connectivity analysis was performed using VTA and SN seeds in another, larger sample (dataset 2) to assess whether neural networks of VTA or SN seeds from dataset 1 would be replicated in dataset 2. The Asian VTA template was smaller and located in a more posterior and inferior part of the midbrain compared to the published VTA template, while the Asian SN template, relative to the published SN template, did not differ in size but was located in the more inferior part of the midbrain. The neural networks of the VTA and SN seeds in dataset 1 were replicated in dataset 2. Altogether, our normalized template of the VTA and SN could be used for measuring fMRI activities related to the VTA and SN in the Asian population.

Highlights

  • Increasing evidence suggests that the midbrain dopaminergic system is involved in various behavioral and cognitive functions, such as motor behavior, working memory, decision making, attention, reward-related learning, addiction, and motivation [1,2,3]

  • Considering that the ventral tegmental area (VTA) and substantia nigra (SN) in the midbrain are the primary dopamine producers, localizing these regions in humans is necessary if future neuroimaging studies are to reveal the role of the midbrain dopamine system

  • The mean volume of the VTA and SN regions of interests (ROIs) across all participants in dataset 1 was 357.63 ± 108.35 mm3 and 1087.70 ± 227.53 mm3, respectively

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Summary

Introduction

Increasing evidence suggests that the midbrain dopaminergic system is involved in various behavioral and cognitive functions, such as motor behavior, working memory, decision making, attention, reward-related learning, addiction, and motivation [1,2,3]. Details of the role of the midbrain dopaminergic system in those functions remain to be determined in humans. Recent remarkable developments of neuroimaging techniques provide the means by which to develop deeper understanding of this dopaminergic system in humans. Considering that the ventral tegmental area (VTA) and substantia nigra (SN) in the midbrain are the primary dopamine producers, localizing these regions in humans is necessary if future neuroimaging studies are to reveal the role of the midbrain dopamine system. Dopamine neurons in the SN project to the dorsal striatum via the nigostriatal pathway. These neurons are critical for controlling voluntary movement and are associated with prediction error and processing saliency of environmental stimuli [4]. Loss of dopamine neurons in the SN is an established cause of Parkinson’s disease, which is characterized by tremor, rigidity, and slowness of movements [5]

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