In vivo mapping of human brainstem vestibular and autonomic pathways

项目摘要/摘要 几十年来，对急性前庭缺陷恢复的研究一直集中在代偿性方面。 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证实，自主神经唤醒和焦虑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、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 相互作用似乎会导致慢性前庭疾病并使之永久化。连接前庭的通路 通过臂旁核到杏仁核的核团和相关的脑干自主神经核团被认为是基础 这些障碍。更多关于前庭-自主神经相互作用的知识，当转化为早期临床时 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进其治疗。进展受阻 关键障碍：脑干前庭-自主神经过程的神经回路在《生活》中被低估了 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 敏感度和对比度定位关键脑干前庭和自主神经核团，如前庭核团 复合体、中脑导水管周围灰质、中缝大核、臂旁外侧核和臂旁内侧核、孤束核。 为了跨越这一障碍，拟议研究的中心目标是在生活健康的受试者中产生一种 标准立体定位下前庭核团和自主神经核团的原始概率神经成像图谱 在休息和前庭刺激期间绘制他们的基准连接图(“Connectome”) 先进的成像技术(7 T和3 T Connectome扫描仪)。这项建议是基于我们最近提出的 发表了在活人身上的7个T工作，产生了两个和 (中脑导水管周围灰质，中缝大核)和其他九个脑干核团的觉醒和运动系统。我们 建议扩展本图谱和连接组，以包括前庭核团复合体和另外三个 自主神经核团(臂旁外侧核、臂旁内侧核和孤束核)，以及使用前庭 刺激以开创性地检验假说驱动脑干前庭和脑干的功能连接改变 自主神经核团。 因此，我们的项目将提供两个重要的新工具，一个结构图集和一个用于研究的连接体 活人前庭核团、多个自主神经核团及其相互作用。本地化能力 神经影像中的前庭和自主神经核团以及生活中前庭-自主神经通路的研究 人类将增强我们对脑干前庭自主神经过程如何与病理- 慢性前庭疾病的生理机制及其治疗效果。

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.