精神分裂症(分裂症)患者工作记忆损害脑影像异常特征尚不清楚，其神经环路受损的遗传及分子机理也不明确。本项目拟在前期重大研究计划重点支持项目的基础上，采用精神病理、分子遗传、脑影像、动物建模、行为评定、光学成像、环路示踪、光遗传调控、电生理、细胞与分子生物等多学科技术方法，围绕“分裂症患者工作记忆障碍的神经环路机制”这一科学问题展开综合性研究，探讨基于“新一代脑网络组图谱”的分裂症工作记忆障碍相关脑网络的影像学异常表征以及非药物治疗(rTMS)对记忆网络的调控、进一步确定与该病工作记忆障碍关联的易感基因/变异、对动物模型记忆神经环路功能异常进行定量定性描述、探讨易感基因/变异所致记忆神经环路异常改变的分子机制。本项目预期结果将建立分裂症工作记忆障碍脑区以及神经环路异常的脑网络模型，初步明确分裂症记忆环路受损的分子机制，并为发展可用于临床诊断和疗效预测的影像遗传生物标志提供重要的实验依据。

Characteristic brain magnetic resonance imaging (MRI) abnormalities in schizophrenic patients with working memory impairment are largely unknown, and genetic and molecular mechanisms of their impaired neural circuits are not well understood as well. The plan of current project is based on the previous research work supported by the Key Program of Major Research Plan from the National Natural Science Foundation (NSFC). We will take advantage of multidisciplinary strategy, by combining technology and methods from psychopathology, molecular genetics, brain imaging, animal modeling, behavioral assessment, optical imaging, neural circuit tracing, optogenetics, electrophysiology, cell and molecular biology etc. Focusing on the mechanism of abnormal neural circuits involved in impaired working memory in patients with schizophrenia, we will carry out a comprehensive study on the scientific issue - “Disorder of working memory, Dysfunction of brain region, Impairment of neural plasticity are the neurobiological features for schizophrenia”. The research work will include investigating the characteristic MRI abnormalities of bran networks related to working memory disorders based on the latest Brainnetome atlas, the regulation effects of repeated transcranial magnetic stimulation (rTMS) on the brain networks of working memory; further determining the susceptibility genes/variations associated with the impaired working memory in schizophrenic patients; mapping the abnormal neural circuits in animal models qualitatively and quantitatively; uncovering the molecular mechanism of abnormal changes of memorial neural circuits caused by the susceptibility genes/variations. The project will establish brain network models of working memory impairment in schizophrenia including abnormalities in brain regions and circuits; preliminarily determine the molecular mechanism of working memory impairment. The expected results will provide important experimental evidence for developing new biomarkers for clinical diagnosis and efficacy prediction of schizophrenia.