Evidence for Altered Basal Ganglia-Brainstem Connections in Cervical Dystonia

BackgroundThere has been increasing interest in the interaction of the basal ganglia with the cerebellum and the brainstem in motor control and movement disorders. In addition, it has been suggested that these subcortical connections with the basal ganglia may help to coordinate a network of regions involved in mediating posture and stabilization. While studies in animal models support a role for this circuitry in the pathophysiology of the movement disorder dystonia, thus far, there is only indirect evidence for this in humans with dystonia. Methodology/Principal FindingsIn the current study we investigated probabilistic diffusion tractography in DYT1-negative patients with cervical dystonia and matched healthy control subjects, with the goal of showing that patients exhibit altered microstructure in the connectivity between the pallidum and brainstem. The brainstem regions investigated included nuclei that are known to exhibit strong connections with the cerebellum. We observed large clusters of tractography differences in patients relative to healthy controls, between the pallidum and the brainstem. Tractography was decreased in the left hemisphere and increased in the right hemisphere in patients, suggesting a potential basis for the left/right white matter asymmetry we previously observed in focal dystonia patients. Conclusions/SignificanceThese findings support the hypothesis that connections between the basal ganglia and brainstem play a role in the pathophysiology of dystonia.背景：目前，学界对基底神经节（basal ganglia）、小脑（cerebellum）与脑干（brainstem）在运动控制及运动障碍中的相互作用关注度与日俱增。此外，有研究提出，这些与基底神经节相连的皮层下连接，或可协调参与维持姿势与稳定的脑区网络。尽管动物模型研究证实，该环路在肌张力障碍（dystonia）这一运动障碍的病理生理学中具有作用，但迄今为止，在肌张力障碍患者中仅能获取间接证据。 研究方法与主要发现：本研究针对DYT1阴性颈肌张力障碍患者及匹配的健康对照受试者开展概率性弥散纤维追踪（probabilistic diffusion tractography）分析，旨在证实患者的苍白球（pallidum）与脑干之间的连接存在微结构改变。本次研究涉及的脑干区域包含已知与小脑存在强连接的神经核团。结果显示，相较于健康对照，患者组在苍白球与脑干之间存在大量弥散追踪差异簇：患者组左侧半球的弥散追踪信号减弱，右侧半球则增强，这为我们此前在局灶性肌张力障碍患者中观察到的左右侧白质不对称性提供了潜在依据。 结论与意义：本研究结果支持“基底神经节与脑干之间的连接在肌张力障碍的病理生理学中发挥作用”这一假说。