In vivo mapping of human brainstem vestibular and autonomic pathways

项目总结/摘要 几十年来，关于急性前庭功能障碍恢复的研究一直集中在代偿性前庭功能障碍上。 脑干前庭核和相关的脑干/小脑通路中的机制。与此相反的是， 最近的前瞻性临床研究确定了自主神经唤醒和焦虑的升高是主要的预测因素 恢复失败和前庭症状延长（例如头晕、失衡、运动过敏 刺激）在急性前庭事件后的慢性前庭疾病中的作用。因此，不利的前庭自主神经 这种相互作用似乎使慢性前庭障碍沉淀并永久化。前庭神经通路 通过臂旁核和相关的脑干自主神经核到达杏仁核被认为是 这些紊乱。更多的前庭自主神经相互作用的知识，当转化为早期临床 干预措施，有望最大限度地恢复急性前庭疾病，一个重要的公共卫生目标， 通过减少慢性前庭疾病的发病率和改善其治疗。进展受阻 一个关键的障碍：脑干前庭自主过程的神经回路在生活中被低估。 人类，尽管在动物模型中进行了广泛的研究。现有的活体脑成像方法缺乏足够的 灵敏度和对比度，以定位关键的脑干前庭和自主神经核，如前庭核 复合体、导水管周围灰质、中缝大核、臂旁外侧核和内侧核以及孤束核。 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一种 标准立体定位空间中前庭和自主神经核的原始概率神经成像图谱， 为了绘制他们在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）。这一建议建立在我们最近 发表了7 T在活体人类中的工作，产生了两个An的概率图谱和连接体。 （中脑导水管周围灰质，中缝大）和其他九个唤醒和运动系统的脑干核团。我们 我建议扩展这个图谱和连接组，包括前庭核复合体和三个额外的 自主神经核（外侧和内侧臂旁核，和孤核），以及使用前庭 刺激，以开创性地测试假设驱动的脑干前庭和 自主神经核 因此，我们的项目将提供两个重要的新工具，结构图谱和连接体研究 前庭神经核，多个自主神经核，以及它们在活人中的相互作用。本地化能力 前庭和自主神经核在神经影像和研究前庭自主神经通路在生活 人类将增强我们对脑干前庭自主过程如何与病理性 导致慢性前庭障碍的生理机制及其治疗结果。

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.