精神分裂症的症状、疗效及关联基因均存在严重异质性。根据脑功能损伤特征将精神分裂症分为高同质性亚型将对理解其病理机制和改善治疗效果产生重大贡献。该目标背后的科学问题是如何不局限于症状学“金标准”，在脑功能损伤特征的变异中探测亚型。申请人的系列工作为此提供了探测神经影像亚型的方法，而进一步凸显精神障碍患者的脑功能损伤特征是回答该问题的另一重要方面。自然刺激，即受试者观看接近生活的电影片段，可最大限度地使脑活动可控地接近日常状态，直接显示受试间脑活动的动态相似性，凸显丰富的脑活动特征。本项目拟引入自然刺激，通过特征增强和特征检测两方面的努力探测精神分裂症的脑功能损伤亚型。本项目将提出自然刺激下的神经影像挖掘新算法、验证其信度和效度、建立自然刺激的临床神经影像数据库，通过数据挖掘发现精神分裂症的脑功能损伤亚型并试图建立其对疗效的预测关系。本项目产出的新方法和数据库亦将为其他精神障碍研究提供资源。

Considerable heterogeneous in schizophrenia is revealed in its symptoms, treatment responses, and associated genes. Subtyping schizophrenia based on brain function deficits would essentially facilitate our understandings of the pathophysiology and advance treatment efficacy for this disabling disease. The underlying scientific question is how to decompose the variance in brain function deficits into subtypes, without the boundaries from symptom-based “golden standard”. To achieve this aim, a series of preceding works of the applicant have established methodologies for subtyping neuroimaging data. The remaining critical aspect for addressing the scientific question is how to further expose the brain function deficits of schizophrenia. Natural stimuli, under which subjects watch movie sceneries, can approach brain activities towards real-life status, while keeping them under control. This paradigm is capable to reflect dynamic inter-individual similarities in brain activities and is thus effective in revealing rich features of brain deficits. The current project brings in natural stimuli, aiming to discover brain deficit subtypes of schizophrenia by advancing both feature enhancement and feature detection. The project will develop novel data-mining methodologies for natural stimuli, examine its reliability and validity, construct clinical neuroimaging database with natural stimuli, propose brain deficit subtypes of schizophrenia through data-mining, and attempt to establish predictive associations between the subtypes and treatment efficacy. The novel methodologies and clinical database produced in this project will also contribute resources to subtyping studies of other mental disorders.