A New fMRI Method to Measure Substantia Nigra Signaling During Reward Processing

一种新的功能磁共振成像方法来测量奖励处理过程中的黑质信号

基本信息

批准号：
8893725
负责人：
JONG H YOON
金额：
$ 21.43万
依托单位：
PALO ALTO VETERANS INSTIT FOR RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-04-01 至 2018-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8893725
关键词：
Affective Basal Ganglia Behavioral Brain Brain region Cell Nucleus Clinical Cognitive Complex Conditioned Reflex Corpus striatum structure Data Development Disease Dopamine Dorsal Failure Fostering Functional Magnetic Resonance Imaging Future Goals Grant Habits Human Image Incentives Iron Lead Learning Link Location Masks Measures Methods Midbrain structure Modeling Morbidity - disease rate Pathogenesis Play Procedures Process Psychological reinforcement Regulation Research Research Personnel Resolution Rewards Role Sampling Scanning Signal Transduction Structure Structure of subthalamic nucleus Substance Addiction Substance abuse problem Substantia nigra structure Testing Treatment Factor United States Validation addiction base blood oxygen level dependent cognitive neuroscience effective therapy experience flexibility image processing imaging modality in vivo neuromechanism neurotransmission novel programs public health relevance relating to nervous system research study reward processing substance abuse treatment tool treatment strategy young adult

项目摘要

DESCRIPTION (provided by applicant): Substance abuse and related conditions are complex, common, and costly disorders. A better understanding of the neural mechanisms giving rise to these conditions may yield valuable clues for the development of new and more effective treatments. While we now know in broad terms that dopamine and its regulation of reward processing are involved in the pathogenesis of substance abuse, there is still much to learn about the details of how dopaminergic mechanisms of reward processing may be subverted and lead to addiction, particularly in human models. The midbrain dopaminergic nuclei are among the most important structures regulating dopamine function because they store and release the majority of dopamine in the brain. Thus, the availability of a flexible, widely available, non-invasive means of measuring their signaling during reward processing in humans could prove to be useful in elucidating dopaminergic mechanisms. However, these nuclei are very difficult to image due to their small size and location. We have recently developed a new, simple, yet precise high resolution fMRI method for measuring the signal from one of the major dopaminergic nuclei, the substantial nigra, a structure that is now recognized to play an important role in reward related processes closely associated with substance abuse and addiction. Using the well-known fact that its high iron content renders the nigra as a distinct region of hypointensity on fMRI volumes, we will use a unique set of image processing steps that have been optimized to localize and distinguish nigra from nearby structures directly on task images. We will then be able to derive estimates of task evoked fMRI signal from as well as verify the localization of significant activity within the nigra. We propose validating this method for use in substance abuse research by testing the hypothesis that it can measure reward processing related nigral signaling. We will scan a sample of healthy young adults while they complete a reward processing task that has been well validated as a driver of reward associated nigral dopamine signaling in humans. We will then compare nigral signal during reward vs. non-reward trials, as well as verify that significant reward activity occurs within the nigra. The successful completion of this project will provide preliminary confirmation of a new fMRI method for measuring dopamine function that may be useful in in vivo human models of substance abuse. In addition, it will alllow the PI to obtain valuable experience in substance abuse research that may enable him to obtain more extensive grants and conduct further research in this field.

描述（由申请人提供）：药物滥用和相关病症是复杂、常见且昂贵的疾病，更好地了解引起这些病症的神经机制可能会为开发新的、更有效的治疗方法提供有价值的线索。尽管从广义上来说，多巴胺及其对奖赏处理的调节与药物滥用的发病机制有关，但关于奖赏处理的多巴胺能机制如何被破坏并导致成瘾的细节，尤其是在人类模型中，仍有很多东西需要了解。这中脑多巴胺能核是调节多巴胺功能的最重要结构之一，因为它们在大脑中储存和释放大部分多巴胺，因此，在人类奖励处理过程中测量其信号传导的灵活、广泛使用、非侵入性方法的可用性可能会有所提高。事实证明，这些核在阐明多巴胺能机制方面非常有用，但由于它们的尺寸和位置都很小，因此我们最近开发了一种新的、简单而精确的高分辨率功能磁共振成像方法，用于测量其中一个主要核的信号。多巴胺能核，即黑质，现在被认为在与药物滥用和成瘾密切相关的奖赏相关过程中发挥重要作用，众所周知，其高铁含量使黑质成为一个独特的低信号区域。在 fMRI 体积上，我们将使用一组独特的图像处理步骤，这些步骤已经过优化，可以直接在任务图像上定位和区分黑质与附近的结构，然后我们将能够从中得出任务诱发的 fMRI 信号的估计并验证该信号。我们建议验证这种方法。通过测试它可以测量奖励处理相关的黑质信号传导的假设，用于药物滥用研究。我们将扫描健康年轻人的样本，同时他们完成奖励处理任务，该任务已被充分验证为奖励相关的黑质多巴胺信号传导的驱动因素。然后，我们将比较奖励试验与非奖励试验期间的黑质信号，并验证黑质内是否发生显着的奖励活动。该项目的成功完成将为测量多巴胺功能的新功能磁共振成像方法提供初步确认。那可能此外，它将使 PI 能够获得药物滥用研究方面的宝贵经验，从而使他能够获得更广泛的资助并在该领域进行进一步的研究。