Chen Hui, Dai Limeng, Zhang Yuhan, Feng Liu, Jiang Zhenzhen, Wang Xingang, Xie Dongjing, Guo Jing, Chen Huafu, Wang Jian, Liu Chen
Department of Radiology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
Department of Medical Genetics, Third Military Medical University (Army Medical University), Chongqing, China.
Front Aging Neurosci. 2022 Apr 11;14:773119. doi: 10.3389/fnagi.2022.773119. eCollection 2022.
Spinocerebellar ataxia type 3 (SCA3) is a rare movement disorder characterized with ataxia. Previous studies on movement disorders show that the whole-brain functional network tends to be more regular, and these reconfigurations correlate with genetic and clinical variables.
To test whether the brain network in patients with SCA3 follows a similar reconfiguration course to other movement disorders, we recruited 41 patients with SCA3 (mean age = 40.51 ± 12.13 years; 23 male) and 41 age and sex-matched healthy individuals (age = 40.10 ± 11.56 years; 24 male). In both groups, the whole-brain network topology of resting-state functional magnetic resonance imaging (rs-fMRI) was conducted using graph theory, and the relationships among network topologies, cytosine-adenine-guanine (CAG) repeats, clinical symptoms, and functional connectivity were explored in SCA3 patients using partial correlation analysis, controlling for age and sex.
The brain networks tended to be more regular with a higher clustering coefficient, local efficiency, and modularity in patients with SCA3. Hubs in SCA3 patients were reorganized as the number of hubs increased in motor-related areas and decreased in cognitive areas. At the global level, small-worldness and normalized clustering coefficients were significantly positively correlated with clinical motor symptoms. At the nodal level, the clustering coefficient and local efficiency increased significantly in the visual (bilateral cuneus) and sensorimotor (right cerebellar lobules IV, V, VI) networks and decreased in the cognitive areas (right middle frontal gyrus). The clustering coefficient and local efficiency in the bilateral cuneus gyrus were negatively correlated with clinical motor symptoms. The functional connectivity between right caudate nucleus and bilateral calcarine gyrus were negatively correlated with disease duration, while connectivity between right posterior cingulum gyrus and left cerebellar lobule III, left inferior occipital gyrus and right cerebellar lobule IX was positively correlated.
Our results demonstrate that a more regular brain network occurred in SCA3 patients, with motor and visual-related regions, such as, cerebellar lobules and cuneus gyrus, both forayed neighbor nodes as "resource predators" to compensate for normal function, with motor and visual function having the higher priority comparing with other high-order functions. This study provides new information about the neurological mechanisms underlying SCA3 network topology impairments in the resting state, which give a potential guideline for future clinical treatments.
[www.ClinicalTrials.gov], identifier [ChiCTR1800019901].
3型脊髓小脑共济失调（SCA3）是一种以共济失调为特征的罕见运动障碍。先前关于运动障碍的研究表明，全脑功能网络倾向于更规则，并且这些重新配置与遗传和临床变量相关。
为了测试SCA3患者的脑网络是否遵循与其他运动障碍相似的重新配置过程，我们招募了41名SCA3患者（平均年龄 = 40.51 ± 12.13岁；23名男性）和41名年龄和性别匹配的健康个体（年龄 = 40.10 ± 11.56岁；24名男性）。在两组中，使用图论对静息态功能磁共振成像（rs-fMRI）的全脑网络拓扑进行分析，并在SCA3患者中使用偏相关分析探索网络拓扑、胞嘧啶-腺嘌呤-鸟嘌呤（CAG）重复序列、临床症状和功能连接之间的关系，同时控制年龄和性别。
SCA3患者的脑网络倾向于更规则，具有更高的聚类系数、局部效率和模块化。随着SCA3患者中枢纽数量在运动相关区域增加而在认知区域减少，枢纽发生了重组。在全局水平上，小世界特性和标准化聚类系数与临床运动症状显著正相关。在节点水平上，视觉（双侧楔叶）和感觉运动（右侧小脑小叶IV、V、VI）网络中的聚类系数和局部效率显著增加，而在认知区域（右侧额中回）则降低。双侧楔叶回中的聚类系数和局部效率与临床运动症状呈负相关。右侧尾状核与双侧距状回之间的功能连接与病程呈负相关，而右侧后扣带回与左侧小脑小叶III、左侧枕下回与右侧小脑小叶IX之间的连接呈正相关。
我们的结果表明，SCA3患者出现了更规则的脑网络，运动和视觉相关区域，如小脑小叶和楔叶回，作为“资源掠夺者”侵入相邻节点以补偿正常功能，与其他高阶功能相比，运动和视觉功能具有更高的优先级。本研究提供了关于静息状态下SCA3网络拓扑损伤潜在神经机制的新信息，为未来的临床治疗提供了潜在指导。
