In vivo mapping of human brainstem vestibular and autonomic pathways

人脑干前庭和自主神经通路的体内绘图

• 批准号: 9386205
• 负责人: Marta Bianciardi
• 金额: $ 25.65万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9386205
• 关键词: Acute; Agreement; Anatomy; Animal Model; Animals; Anxiety; Arousal; Atlases; Autonomic Pathways; Behavior; Benchmarking; Brain Stem; Brain imaging; Cell Nucleus; Chronic; Clinical; Clinical Research; Complex; Data; Diagnosis; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Dizziness; Echo-Planar Imaging; Event; Foundations; Functional Imaging; Future; Goals; Gold; Human; Hypersensitivity; Image; Imaging technology; Incidence; Intervention; Knowledge; Label; Lateral; Link; Magnetic Resonance Imaging; Manuals; Maps; Measures; Medial; Methods; Modeling; Motion; Motor; Nucleus solitarius; Pathologic; Pathologic Processes; Pathway interactions; Physiological; Predisposition; Prevention; Process; Public Health; Publishing; Recovery; Research; Resolution; Rest; Stimulus; Structure; Symptoms; System; Technology; Testing; Translating; Treatment outcome; Vestibular nucleus structure; Work; base; connectome; contrast imaging; imaging modality; improved; in vivo; midbrain central gray substance; neural circuit; neuroimaging; novel; parabrachial nucleus; prospective; tool; vestibular pathway; vestibulo-ocular reflex

PROJECT SUMMARY/ABSTRACT For decades, research on recovery from acute vestibular deficits has focused on compensatory mechanisms in the brainstem vestibular nuclei and associated brainstem/cerebellar pathways. In contrast, recent prospective clinical studies identified elevated autonomic arousal and anxiety as the primary predictors of failed recovery and prolonged vestibular symptoms (e.g. dizziness, imbalance, hypersensitivity to motion stimuli) in chronic vestibular disorders following acute vestibular events. Thus, adverse vestibular-autonomic interactions appear to precipitate and perpetuate chronic vestibular disorders. Pathways linking vestibular nuclei to the amygdalae via parabrachial and associated brainstem autonomic nuclei are thought to underlie these disorders. Greater knowledge of vestibular-autonomic interactions, when translated into early clinical interventions, promises to maximize recovery from acute vestibular disorders, an important public health goal, by reducing the incidence of chronic vestibular disorders and improving their treatment. Progress is hampered by a critical barrier: neural circuitry of brainstem vestibular-autonomic processes is underspecified in living humans, despite extensive research in animal models. Existing in vivo brain imaging methods lack sufficient sensitivity and contrast to localize key brainstem vestibular and autonomic nuclei, such as the vestibular nuclei complex, periaqueductal gray, raphe magnus, lateral and medial parabrachial nuclei, and solitary nucleus. To surmount this barrier, the central aim of the proposed research is to generate in living healthy subjects an original probabilistic neuroimaging atlas of vestibular and autonomic nuclei in standard stereotaxic space and to map their benchmark connectivity diagram (“connectome”) at rest and during vestibular stimulation using advanced imaging technology (7 T and 3 T Connectome scanners). This proposal builds on our recently published 7 T work in living humans, which yielded the probabilistic atlas and connectome of two An (periaqueductal gray, raphe magnus) and nine other brainstem nuclei of the arousal and motor systems. We propose to extend this atlas and connectome to include the vestibular nuclei complex and three additional autonomic nuclei (lateral and medial parabrachial nuclei, and solitary nucleus), as well as to use vestibular stimulation to pioneeringly test hypothesis driven functional connectivity changes in brainstem vestibular and autonomic nuclei. Thus, our project will provide two important new tools, a structural atlas and connectome for studying the vestibular nuclei, multiple autonomic nuclei, and their interactions in living humans. The ability of localizing vestibular and autonomic nuclei in neuroimages and of investigating vestibular-autonomic pathways in living humans will enhance our understanding of how brainstem vestibular-autonomic processes relate to the patho- physiologic mechanism causing chronic vestibular disorders and to their treatment outcomes.

项目概要/摘要 几十年来，关于急性前庭缺陷恢复的研究一直集中在代偿性前庭功能障碍上。 脑干前庭核团和相关脑干/小脑通路的机制。相比之下， 最近的前瞻性临床研究确定自主神经唤醒和焦虑升高是主要预测因素 恢复失败和长期前庭症状（例如头晕、不平衡、对运动过敏） 刺激）在急性前庭事件后的慢性前庭疾病中。因此，不利的前庭自主神经 相互作用似乎会引发并延续慢性前庭疾病。连接前庭的通路 通过臂旁核和相关脑干自主核到达杏仁核被认为是基础 这些疾病。对前庭自主相互作用的更多了解，转化为早期临床 干预措施，承诺最大限度地从急性前庭疾病中恢复，这是一个重要的公共卫生目标， 通过减少慢性前庭疾病的发生率并改善其治疗。进展受到阻碍 通过一个关键障碍：脑干前庭自主过程的神经回路在生活中未明确 尽管对动物模型进行了广泛的研究，但人类。现有的体内脑成像方法缺乏足够的 定位关键脑干前庭和自主神经核（例如前庭核）的灵敏度和对比度 复合体、导水管周围灰质、中缝大核、外侧和内侧臂旁核以及孤立核。 为了克服这一障碍，拟议研究的中心目标是在健康的受试者中产生 标准立体定位空间中前庭和自主神经核的原始概率神经影像图谱 使用以下方法绘制休息时和前庭刺激期间的基准连接图（“连接组”） 先进的成像技术（7 T 和 3 T Connectome 扫描仪）。该提案建立在我们最近 发表了 7 T 活体人类工作，产生了两个 An 的概率图谱和连接组 （导水管周围灰质、中缝大核）和唤醒和运动系统的其他九个脑干核团。我们 建议扩展该地图集和连接组以包括前庭核复合体和另外三个 自主神经核（外侧和内侧臂旁核和孤立核），以及使用前庭神经核 刺激以开创性地测试假设驱动的脑干前庭和功能连接变化 自主神经核。 因此，我们的项目将提供两个重要的新工具，结构图谱和连接组用于研究 前庭核、多个自主神经核及其在活人体内的相互作用。本地化能力 神经图像中的前庭和自主神经核以及研究生活中的前庭自主通路 人类将增强我们对脑干前庭自主过程如何与病理相关的理解 导致慢性前庭疾病的生理机制及其治疗结果。