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: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=740707
• 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来更好地理解人脑中神经递质多巴胺的功能。我最近的工作已经验证了一种专门的磁共振成像（MRI）方法，神经黑色素敏感MRI （NM-MRI）作为多巴胺功能的测量，而不仅仅是作为多巴胺系统损伤的标志，如以前使用的。这一发现为这项技术的新应用提供了更先进的开发工作和研究，包括许多由于缺乏实用工具而在活人大脑中使用的知识受到限制的领域。重要的是，与传统的多巴胺PET成像不同，纳米核磁共振成像是非侵入性的。因此，纳米核磁共振成像可用于PET成像无法获得的应用，例如青年研究或随时间重复评估的纵向研究。纳米核磁共振成像具有很高的解剖分辨率，揭示了参与情绪、认知和运动行为的不同多巴胺神经元群。神经黑色素（NM）是一种由纳米核磁共振检测到的化合物，是一种由多巴胺分解产生的深色色素。它在出生时不存在，并在一生中逐渐积累在多巴胺神经元中，为多巴胺活动的历史提供了永久的记录。我们首次在儿童和青少年中检测纳米核磁共振信号：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性大脑发育的相关性。我们将获取儿童和青少年以及年轻人和老年人在多个时间点的核磁共振成像扫描和行为和环境测量结果进行比较。该研究项目的一个组成部分将测试纳米核磁共振成像信号在生命早期和后期随时间的变化模式，并比较男性和女性的这些动态。拟议研究的另一个组成部分将调查纳米信号与行为、认知表现和已知由多巴胺调节的环境条件的关系。为了支持这项工作，研究项目将进一步完善纳米核磁共振成像的方法。这包括获取和分析纳米核磁共振扫描的方法，检验其与大脑化学成分关系的验证工作（使用死后组织），以及开发改进的方法，将纳米核磁共振可视化的多巴胺神经元分为情感、认知和运动亚组，使用基于个体大脑连接模式的个性化信息。纳米核磁共振成像正在成为神经科学和实验心理学的标准神经成像工具。拟议的研究将支持进一步改进该方法并发现这种新方法的新应用，特别是在人类大脑发育方面，目前很少有工具可以研究多巴胺等关键神经递质的影响。