Involvement of the cerebellum in structural connectivity enhancement in episodic migraine

Ana Matoso, Ana R. Fouto, Inês Esteves, Amparo Ruiz-Tagle, Gina Caetano, Nuno A. da Silva, Pedro Vilela, Raquel Gil-Gouveia, Rita G. Nunes, Patrícia Figueiredo
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Abstract

The pathophysiology of migraine remains poorly understood, yet a growing number of studies have shown structural connectivity disruptions across large-scale brain networks. Although both structural and functional changes have been found in the cerebellum of migraine patients, the cerebellum has barely been assessed in previous structural connectivity studies of migraine. Our objective is to investigate the structural connectivity of the entire brain, including the cerebellum, in individuals diagnosed with episodic migraine without aura during the interictal phase, compared with healthy controls. To that end, 14 migraine patients and 15 healthy controls were recruited (all female), and diffusion-weighted and T1-weighted MRI data were acquired. The structural connectome was estimated for each participant based on two different whole-brain parcellations, including cortical and subcortical regions as well as the cerebellum. The structural connectivity patterns, as well as global and local graph theory metrics, were compared between patients and controls, for each of the two parcellations, using network-based statistics and a generalized linear model (GLM), respectively. We also compared the number of connectome streamlines within specific white matter tracts using a GLM. We found increased structural connectivity in migraine patients relative to healthy controls with a distinct involvement of cerebellar regions, using both parcellations. Specifically, the node degree of the posterior lobe of the cerebellum was greater in patients than in controls and patients presented a higher number of streamlines within the anterior limb of the internal capsule. Moreover, the connectomes of patients exhibited greater global efficiency and shorter characteristic path length, which correlated with the age onset of migraine. A distinctive pattern of heightened structural connectivity and enhanced global efficiency in migraine patients compared to controls was identified, which distinctively involves the cerebellum. These findings provide evidence for increased integration within structural brain networks in migraine and underscore the significance of the cerebellum in migraine pathophysiology.
小脑参与发作性偏头痛的结构连接增强
人们对偏头痛的病理生理学仍然知之甚少,但越来越多的研究显示,大规模大脑网络的结构连接出现了紊乱。虽然在偏头痛患者的小脑中发现了结构和功能变化,但在以往的偏头痛结构连通性研究中几乎没有对小脑进行评估。我们的目的是研究被诊断为发作性无先兆偏头痛患者在发作间期与健康对照组相比,包括小脑在内的整个大脑的结构连通性。为此,研究人员招募了 14 名偏头痛患者和 15 名健康对照者(均为女性),并采集了弥散加权和 T1 加权磁共振成像数据。根据两个不同的全脑区,包括皮层和皮层下区域以及小脑,对每位参与者的结构连接组进行了估算。我们分别使用基于网络的统计方法和广义线性模型(GLM)比较了患者和对照组在两个小区中的结构连接模式以及全局和局部图论指标。我们还使用 GLM 比较了特定白质束内的连接组流线数量。我们发现,与健康对照组相比,偏头痛患者的结构连通性增加了,小脑区域明显受累。具体来说,患者小脑后叶的节点程度高于对照组,患者内囊前肢的流线数量也更多。此外,患者的连接组显示出更高的全局效率和更短的特征路径长度,这与偏头痛的发病年龄有关。与对照组相比,偏头痛患者的结构连通性增强,全局效率提高,其中明显涉及小脑。这些发现为偏头痛患者大脑结构网络的整合性增强提供了证据,并强调了小脑在偏头痛病理生理学中的重要性。
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