Novel MRI tools tracking developmental change within the dopamine system in children and adults

新型 MRI 工具可追踪儿童和成人多巴胺系统的发育变化

• 批准号: RGPIN-2020-06127
• 负责人: Cassidy, Clifford
• 金额: $ 2.04万
• 依托单位: University of Ottawa
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=717729
• 关键词: Novel; MRI; tools; tracking; developmental

My research program develops improved methods to better understand the function of the neurotransmitter dopamine in the human brain. My recent work has validated a specialized magnetic resonance imaging (MRI) method, neuromelanin-sensitive MRI (NM-MRI) as a measure of dopamine function, not only as a marker of damage to the dopamine system, as previously used. This discovery allows more advanced development work and investigation of novel applications for this technology, including many where knowledge has been limited by the lack of practical tools to use in living human brain. Importantly, NM-MRI is non-invasive, unlike traditional dopamine PET imaging. Thus, NM-MRI can be used for applications not accessible to PET imaging, such as studies in youth or longitudinal studies with repeated assessment over time. NM-MRI has high anatomical resolution, revealing distinct groups of dopamine neurons involved in emotional, cognitive, and motor behaviors. Neuromelanin (NM), the compound detected by NM-MRI, is a dark pigment created from the breakdown of dopamine. It is absent at birth and progressively accumulates in dopamine neurons over the lifespan, providing a permanent record of the history of dopamine activity. We propose to examine for the first time the NM-MRI signal in children and adolescents: to measure the signal longitudinally and investigate its relevance to experience-dependent brain development via its relationship to behavior and environmental conditions. We will acquire NM-MRI scans and behavioral and environmental measures at multiple time points in children and adolescents and also in young and older adults for comparison. One component of the research program will test the pattern of NM-MRI signal changes over time during early and later life stages and compare these dynamics in males and females. Another component of the proposed research will investigate the relationship of the NM-signal to behavior, cognitive performance, and environmental conditions known to be regulated by dopamine. To support this work the research program will further refine the methods used for NM-MRI. This includes methods to acquire and analyze NM-MRI scans, validation work examining its relationship to the chemical content of the brain (using post-mortem tissue), and developing improved methods to separate dopamine neurons, visualized with NM-MRI, into emotional, cognitive, and motor subgroups using personalized information based on individual patterns of brain connectivity. NM-MRI is on the path to becoming a standard neuroimaging tool in neuroscience and experimental psychology. The proposed research will support further refinement of the method and discovery of novel applications for this new method, particularly in regards to human brain development, where few tools exist to investigate the influence of key neurotransmitters such as dopamine.

我的研究项目开发了改进的方法，以更好地了解人类大脑中神经递质多巴胺的功能。我最近的工作验证了一种专门的磁共振成像(MRI)方法--神经黑素敏感MRI(NM-MRI)--作为衡量多巴胺功能的指标，而不仅仅是像以前使用的那样，作为多巴胺系统受损的标志。这一发现允许对这项技术进行更高级的开发工作和新应用的研究，包括许多由于缺乏用于活的人脑的实用工具而限制了知识的领域。重要的是，与传统的多巴胺PET成像不同，NM-MRI是非侵入性的。因此，NM-MRI可以用于PET成像无法获得的应用，例如青年研究或随着时间的推移而重复评估的纵向研究。NM-MRI具有很高的解剖分辨率，显示了参与情绪、认知和运动行为的不同组多巴胺神经元。 神经黑素(NM)是由NM-MRI检测到的化合物，是一种由多巴胺分解产生的黑色色素。它在出生时就不存在，并在一生中逐渐积累在多巴胺神经元中，提供了多巴胺活动史的永久记录。我们建议首次在儿童和青少年中检查NM-MRI信号：纵向测量信号，并通过其与行为和环境条件的关系来研究其与经验依赖型大脑发育的相关性。我们将在儿童和青少年以及年轻人和老年人的多个时间点进行NM-MRI扫描和行为和环境测量，以进行比较。研究计划的一个组成部分将测试NM-MRI信号在生命早期和后期随时间变化的模式，并比较男性和女性的这些动态。这项拟议研究的另一个组成部分将调查NM信号与行为、认知表现和已知受多巴胺调节的环境条件的关系。为了支持这项工作，该研究计划将进一步完善用于NM-MRI的方法。这包括获取和分析NM-MRI扫描的方法，验证工作检查其与大脑化学成分的关系(使用尸检组织)，以及开发改进的方法，使用基于大脑连接的个人模式的个性化信息，将NM-MRI可视化的多巴胺神经元分为情绪、认知和运动亚群。 NM-MRI正在成为神经科学和实验心理学中的标准神经成像工具。拟议中的研究将支持该方法的进一步改进和这一新方法的新应用，特别是在人脑发育方面，因为在人脑发育方面，几乎没有工具来研究多巴胺等关键神经递质的影响。