Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow, Russia.
Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow, Russia.
Prog Brain Res. 2019;249:261-268. doi: 10.1016/bs.pbr.2019.03.030. Epub 2019 Apr 30.
Cervical dystonia (CD) is characterized by abnormal twisting and turning of the head with associated head oscillations. It is the most common form of dystonia, which is a third most common movement disorder. Despite frequent occurrence there is paucity in adequate therapy, much of which is attributed to its uncertain pathophysiology. Recently we proposed a unifying network model highlighting the role of head neural integrator (hNI) for the pathophysiology of CD. According to our hypothesis the CD is due to abnormal output of hNI; the latter itself is not affected but its dysfunction is secondary to abnormal feedback. We hypothesized that asymmetry in the feedback to hNI is associated with severity in CD; the feedback asymmetry is greater in CD with lateralized head postures, such as turning of head in yaw plane (torticollis) or roll plane (laterocollis). The hypothesis also specifies that feedback to hNI-cerebellum, proprioception, and basal ganglia outflow (pallidus) are connected in a network; thus asymmetry is distributed through the feedback network. In 15 CD patients undergoing deep brain stimulation (DBS) surgery, with their informed consent, we used the opportunity to collect single unit neural responses and local field potential from the globus pallidus to measure whether feedback to hNI is asymmetric. Using machine learning algorithms developed to analyze single unit data, we found: (1) globus pallidus interna (GPi) firing rate, discharge pattern and gamma oscillation were asymmetric in patients with robust torticollis; (2) there was no asymmetry in these parameters in retrocollis; and (3) in those patients with oppositely directed laterocollis and torticollis. Firing rate was higher in GPi cells ipsilateral to the direction of head rotation; the asymmetry was more pronounced in tonic cells compared to burst neurons. In addition to confirming that CD is associated with an asymmetric pallidal activity, our data showed that neuronal asymmetry correlated with the degree of involuntary head turning. We propose that asymmetric pallidal activity results in asymmetric feedback to hNI causing its dysfunction.
颈部肌张力障碍（CD）的特征是头部异常扭曲和转动，并伴有头部摆动。它是最常见的肌张力障碍形式，也是第三大常见的运动障碍。尽管经常发生，但缺乏足够的治疗方法，其中大部分归因于其不确定的病理生理学。最近，我们提出了一个统一的网络模型，强调头部神经整合器（hNI）在 CD 病理生理学中的作用。根据我们的假设，CD 是由于 hNI 的异常输出；后者本身不受影响，但由于异常反馈，其功能障碍是继发的。我们假设 hNI 的反馈不对称与 CD 的严重程度有关；在具有侧向头部姿势的 CD 中，如在偏航平面（斜颈）或滚动平面（侧斜颈）中转头，反馈不对称性更大。该假设还指定 hNI-小脑、本体感受和基底神经节传出（苍白球）反馈连接在一个网络中；因此，不对称性分布在反馈网络中。在 15 名接受深部脑刺激（DBS）手术的 CD 患者中，在他们知情同意的情况下，我们利用这个机会从苍白球收集单个单位的神经反应和局部场电位，以测量 hNI 的反馈是否不对称。使用开发来分析单个单位数据的机器学习算法，我们发现：（1）在严重斜颈的患者中，内苍白球（GPi）的放电率、放电模式和伽马振荡是不对称的；（2）在反斜颈患者中没有这些参数的不对称性；（3）在那些具有相反方向的侧斜颈和斜颈的患者中。头部旋转方向同侧的 GPi 细胞的放电率较高；与爆发神经元相比，紧张细胞的不对称性更为明显。除了证实 CD 与不对称苍白球活动有关外，我们的数据还表明，神经元不对称性与非自愿头部转动的程度相关。我们提出，不对称的苍白球活动导致 hNI 的不对称反馈，从而导致其功能障碍。
