Schizophrenia Exhibits Bi-directional Brain-Wide Alterations in Cortico-Striato-Cerebellar Circuits
Schizophrenia Exhibits Bi-directional Brain-Wide Alterations in Cortico-Striato-Cerebellar Circuits
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DOI：
10.1093/cercor/bhy306
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发表时间：
2019-11-01
期刊：
影响因子：
3.7
通讯作者：
Anticevic, Alan
中科院分区：
文献类型：
--
作者：
Ji, Jie Lisa;Diehl, Caroline;Anticevic, Alan
分布式神经连接异常被认为是精神分裂症（SCZ）的一个标志性特征，然而，指出局部紊乱的研究与暗示全脑紊乱的研究之间存在矛盾。小脑和纹状体通过单突触和多突触连接与丘脑和皮质相互交流，形成皮质 - 纹状体 - 丘脑 - 小脑（CSTC）功能通路，这些通路可能对精神分裂症中的全脑连接异常敏感。目前尚不清楚相同的改变模式是否在CSTC系统中持续存在，或者这些网络的关键功能元件是否存在特定的改变。我们利用静息态功能磁共振成像对159名慢性患者和162名匹配的对照者的主要功能性CSTC分区的连接性进行了表征。关联性CSTC分区显示患者存在一致的全脑双向改变，其特征是与感觉运动皮质的超连接以及与联合皮质的低连接。着眼于小脑和纹状体成分，我们利用基于数据驱动的体素水平连接异常的k - 均值聚类和支持向量机分类器验证了这些效应。我们在202名对照者和145名患者的独立样本中重复了这些结果，此外还证明了这些神经效应与受试者的认知表现有关。综合来看，这些互补方法的结果表明精神分裂症中CSTC系统存在全脑改变的一致模式，这对仅存在局部功能紊乱的说法提出了质疑。
Distributed neural dysconnectivity is considered a hallmark feature of schizophrenia (SCZ), yet a tension exists between studies pinpointing focal disruptions versus those implicating brain-wide disturbances. The cerebellum and the striatum communicate reciprocally with the thalamus and cortex through monosynaptic and polysynaptic connections, forming cortico-striatal-thalamic-cerebellar (CSTC) functional pathways that may be sensitive to brain-wide dysconnectivity in SCZ. It remains unknown if the same pattern of alterations persists across CSTC systems, or if specific alterations exist along key functional elements of these networks. We characterized connectivity along major functional CSTC subdivisions using resting-state functional magnetic resonance imaging in 159 chronic patients and 162 matched controls. Associative CSTC subdivisions revealed consistent brain-wide bi-directional alterations in patients, marked by hyper-connectivity with sensory-motor cortices and hypo-connectivity with association cortex. Focusing on the cerebellar and striatal components, we validate the effects using data-driven k-means clustering of voxel-wise dysconnectivity and support vector machine classifiers. We replicate these results in an independent sample of 202 controls and 145 patients, additionally demonstrating that these neural effects relate to cognitive performance across subjects. Taken together, these results from complementary approaches implicate a consistent motif of brain-wide alterations in CSTC systems in SCZ, calling into question accounts of exclusively focal functional disturbances.