Along the pathway from behavioral symptoms to the development of psychotic disorders sits the multivariate mediating brain. The functional organization and structural topography of large-scale multivariate neural mediators among patients with brain disorders, however, are not well understood. Here, we design a high-dimensional brain-wide functional mediation framework to investigate brain regions that intermediate between baseline behavioral symptoms and future conversion to full psychosis among individuals at clinical high risk (CHR). Using resting-state functional magnetic resonance imaging (fMRI) data from 263 CHR subjects, we extract an α brain atlas and a β brain atlas: the former underlines brain areas associated with prodromal symptoms and the latter highlights brain areas associated with disease onset. In parallel, we identify and separate mediators that potentially positively and negatively mediate symptoms and psychosis, respectively, and quantify the effect of each neural mediator on disease development. Taken together, these results paint a brain-wide picture of neural markers that are potentially regulating behavioral symptoms and the development of psychotic disorders; additionally, they underscore a statistical framework that is useful to uncover large-scale intermediating variables in a regulatory biological system.

中文翻译：

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识别介导行为症状和精神病发作的神经特征：高维全脑功能中介分析

在从行为症状到精神病发展的过程中，存在着多元中介大脑。然而，脑部疾病患者中大规模多元神经介质的功能组织和结构地形尚不清楚。在这里，我们设计了一个高维的全脑功能调解框架，以研究临床高危 (CHR) 个体中介于基线行为症状和未来转变为完全精神病之间的大脑区域。使用来自 263 名 CHR 受试者的静息状态功能磁共振成像 (fMRI) 数据，我们提取了 α 脑图谱和 β 脑图谱：前者强调与前驱症状相关的大脑区域，后者强调与疾病发作相关的大脑区域。在平行下，我们分别识别和分离可能积极和消极地调节症状和精神病的介质，并量化每种神经介质对疾病发展的影响。综上所述，这些结果描绘了一幅全脑神经标志物的图景，这些神经标志物可能调节行为症状和精神病的发展；此外，它们强调了一个统计框架，该框架有助于揭示监管生物系统中的大规模中介变量。