Department of Psychiatry, Nagoya University, Graduate School of Medicine, Nagoya, Aichi, Japan.
Brain & Mind Research Center, Nagoya University, Nagoya, Aichi, Japan; Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
Neuroimage Clin. 2022;35:103140. doi: 10.1016/j.nicl.2022.103140. Epub 2022 Aug 4.
Schizophrenia is considered a brain connectivity disorder in which functional integration within the brain fails. Central to the brain's integrative function are connector hubs, brain regions characterized by strong connections with multiple networks. Given their critical role in functional integration, we hypothesized that connector hubs, including those located in the cerebellum and subcortical regions, are severely impaired in patients with schizophrenia.
We identified brain voxels with significant connectivity alterations in patients with schizophrenia (n = 76; men = 43) compared to healthy controls (n = 80; men = 43) across multiple large-scale resting state networks (RSNs) using a network metric called functional connectivity overlap ratio (FCOR). From these voxels, candidate connector hubs were identified and verified using seed-based connectivity analysis.
We found that most networks exhibited connectivity alterations in the patient group. Specifically, connectivity with the basal ganglia and high visual networks was severely affected over widespread brain areas in patients, affecting subcortical and cerebellar regions and the regions involved in visual and sensorimotor processing. Furthermore, we identified critical connector hubs in the cerebellum, midbrain, thalamus, insula, and calcarine with connectivity to multiple RSNs affected in the patients. FCOR values of these regions were also associated with clinical data and could classify patient and control groups with > 80 % accuracy.
These findings highlight the critical role of connector hubs, particularly those in the cerebellum and subcortical regions, in the pathophysiology of schizophrenia and the potential role of FCOR as a clinical biomarker for the disorder.
精神分裂症被认为是一种脑连接障碍，其中大脑的功能整合失败。大脑整合功能的核心是连接枢纽，这些区域与多个网络有很强的连接。鉴于它们在功能整合中的关键作用，我们假设连接枢纽，包括位于小脑和皮质下区域的连接枢纽，在精神分裂症患者中受到严重损害。
我们使用一种称为功能连接重叠比（FCOR）的网络度量方法，在多个大型静息态网络（RSN）中，确定了精神分裂症患者（n=76；男性=43）与健康对照组（n=80；男性=43）之间具有显著连接改变的脑体素。从这些体素中，使用基于种子的连接分析来识别和验证候选连接枢纽。
我们发现大多数网络在患者组中都表现出连接改变。具体来说，与基底节和高视觉网络的连接在患者中广泛的脑区受到严重影响，影响了皮质下和小脑区域以及涉及视觉和感觉运动处理的区域。此外，我们确定了小脑、中脑、丘脑、脑岛和距状裂中关键的连接枢纽，这些区域与多个受影响的 RSN 有连接。这些区域的 FCOR 值也与临床数据相关，并且可以以超过 80%的准确率对患者和对照组进行分类。
这些发现强调了连接枢纽的关键作用，特别是小脑和皮质下区域的连接枢纽，在精神分裂症的病理生理学中的作用，以及 FCOR 作为该疾病临床生物标志物的潜在作用。
