Berman Rebecca A, Gotts Stephen J, McAdams Harrison M, Greenstein Dede, Lalonde Francois, Clasen Liv, Watsky Rebecca E, Shora Lorie, Ordonez Anna E, Raznahan Armin, Martin Alex, Gogtay Nitin, Rapoport Judith
1 Child Psychiatry Branch, National Institute of Mental Health, NIH, Bethesda MD 20892, USA
2 Laboratory of Brain and Cognition, National Institute of Mental Health, NIH, Bethesda MD 20892, USA.
Brain. 2016 Jan;139(Pt 1):276-91. doi: 10.1093/brain/awv306. Epub 2015 Oct 22.
Schizophrenia is increasingly recognized as a neurodevelopmental disorder with altered connectivity among brain networks. In the current study we examined large-scale network interactions in childhood-onset schizophrenia, a severe form of the disease with salient genetic and neurobiological abnormalities. Using a data-driven analysis of resting-state functional magnetic resonance imaging fluctuations, we characterized data from 19 patients with schizophrenia and 26 typically developing controls, group matched for age, sex, handedness, and magnitude of head motion during scanning. This approach identified 26 regions with decreased functional correlations in schizophrenia compared to controls. These regions were found to organize into two function-related networks, the first with regions associated with social and higher-level cognitive processing, and the second with regions involved in somatosensory and motor processing. Analyses of across- and within-network regional interactions revealed pronounced across-network decreases in functional connectivity in the schizophrenia group, as well as a set of across-network relationships with overall negative coupling indicating competitive or opponent network dynamics. Critically, across-network decreases in functional connectivity in schizophrenia predicted the severity of positive symptoms in the disorder, such as hallucinations and delusions. By contrast, decreases in functional connectivity within the social-cognitive network of regions predicted the severity of negative symptoms, such as impoverished speech and flattened affect. These results point toward the role that abnormal integration of sensorimotor and social-cognitive processing may play in the pathophysiology and symptomatology of schizophrenia.
精神分裂症越来越被认为是一种神经发育障碍,其大脑网络之间的连接性发生改变。在当前的研究中,我们研究了儿童期起病的精神分裂症中的大规模网络相互作用,这是该疾病的一种严重形式,具有显著的遗传和神经生物学异常。通过对静息态功能磁共振成像波动进行数据驱动分析,我们对19例精神分裂症患者和26名发育正常的对照者的数据进行了特征描述,两组在年龄、性别、利手以及扫描期间头部运动幅度方面进行了匹配。这种方法确定了与对照组相比,精神分裂症患者中功能相关性降低的26个区域。这些区域被发现组织成两个与功能相关的网络,第一个网络包含与社会和高级认知处理相关的区域,第二个网络包含涉及躯体感觉和运动处理的区域。对网络间和网络内区域相互作用的分析显示,精神分裂症组的功能连接性在网络间显著降低,以及一组网络间关系呈现出整体负耦合,表明存在竞争性或对抗性网络动态。至关重要的是,精神分裂症患者网络间功能连接性的降低预示着该疾病中阳性症状的严重程度,如幻觉和妄想。相比之下,区域社会认知网络内功能连接性的降低预示着阴性症状的严重程度,如言语贫乏和平淡的情感。这些结果表明感觉运动和社会认知处理的异常整合在精神分裂症的病理生理学和症状学中可能发挥的作用。