首发精神分裂症基于事件前瞻记忆缺陷的神经活动时空模式研究

Prospective memory (PM) is the ability to remember to carry out intended actions in the future，which plays an important role in functional outcomes of patients with schizophrenia. The accumulated evidence has verified that PM deficits in patients with schizophrenia are independent of other cognitive deficits, and our recently published PM study in patients with drug-na?ve first-episode psychosis also suggested that event-based PM in schizophrenia appears to be a primary deficit. Based on the process model, PM can be divided into four phases: intention formation, intention retention, intention initiation and intention execution, of which the third stage involves cue identification and intention retrieval. It is suggested that PM deficits in schizophrenia might arise from intention initiation impairments, However, the underlying mechanism of cue identification and intention retrieval alterations remains unclear and need further investigation.In the present study, first-episode schizophrenia patients will be included to control confounders. First, we intend to use behavioral experiments, including two PM tasks(a cue identification PM task and an intention retrieval PM task) and other neurocognitive function tasks, to explore the role and relationship of cue identification and intention retrieval in PM deficits in first-episode schizophrenia. Second, abnormal neural circuits as the underlying mechanism of PM deficits in schizophrenia will be studied via the multi-modal MRI techniques, including structural MRI, resting-state fMRI, task fMRI and DTI. The structural connectivity and functional connectivity of the rostral prefrontal cortex will be especially investigated in order to understand the different roles of the medial and lateral rostral prefrontal cortex in PM deficits in schizophrenia. Third, the temporal dynamics and related spatial distribution of PM deficits in schizophrenia will be studied using the event-related potential(ERP). Fouth, to establish the processing stage and spatial distribution of the altered neural activity associated with the PM deficits in schizophrenia via synchronized ERP and task fMRI analysis. Our present study will uncover the altered spatiotemporal patterns of neural activity of event-based PM in schizophrenia, which will help to explore the etiology of schizophrenia and find potential targets for treatment of PM deficits in schizophrenia to improve functional outcomes.

前瞻记忆（PM）缺陷是精神分裂症功能预后的重要影响因素。研究提示精神分裂症PM缺陷源于意向激活阶段（包括线索识别和意向提取)，但精神分裂症意向激活缺陷的机制未明。我们前期研究揭示精神分裂症的基于事件PM为原发性缺陷，且慢性精神分裂症患者的线索识别和意向提取均有缺陷。本项目拟对首发精神分裂症患者研究：①应用行为学方法，探索线索识别和意向提取在精神分裂症PM缺陷中的关系，②应用多模态MRI影像技术，研究精神分裂症线索识别缺陷和意向提取缺陷的神经病理基础，建立精神分裂症PM缺陷的脑连接模型，③应用ERP（与任务态fMRI同步采集数据），明确精神分裂症PM缺陷的时间阶段及神经活动的空间分布，④将ERP分析的神经活动时空模式与fMRI建立的脑连接模型相互验证和补充，建立精神分裂症基于事件PM缺陷的神经活动的时空模型。该项目有助于揭示精神分裂症的病理机制，为功能康复提供新靶点及实验依据。

前瞻记忆（PM）缺陷是精神分裂症功能预后的重要影响因素,既往研究揭示精神分裂症存在PM缺陷，但机制未明。.本项目以首发精神分裂症患者作为研究对象进行研究：① 应用行为学方法探索线索识别和意向提取在精神分裂症PM缺陷中的关系，② 应用多模态MRI影像技术建立精神分裂症PM缺陷的脑连接模型，应用ERP明确精神分裂症PM缺陷的时间阶段及神经活动的空间分布，将ERP分析的神经活动时空模式与fMRI建立的脑连接模型结合起来分析，建立精神分裂症基于事件PM缺陷的神经活动的时空模型。.主要结果：① 首发精神分裂症的线索识别与意向提取均存在缺陷，在控制其他认知功能（工作记忆与回溯记忆）后，线索识别的组间差异仍然存在，而意向提取的组间差异消失，支持精神分裂症的PM缺陷源自于线索识别缺陷与意向提取缺陷的共同作用，线索识别缺陷是精神分裂症的原发性认知缺陷。② 结合结构MRI及DTI研究发现精神分裂症的灰质异常出现较早，而白质异常出现在首次发作后的数年内；右侧海马体积萎缩是精神分裂症早期的唯一变化，而双侧海马结构，右侧额中回及契前叶，左侧枕叶下部逐渐出现体积萎缩。③ 前瞻记忆主要激活左侧额上回、额中回、中央后回及扣带回前部，右侧楔前叶、顶下小叶及枕叶，以及双侧颞上回，而精神分裂症的双侧额中回，右侧枕叶及扣带区后部激活减弱。④ 在线索识别任务中，额叶及顶叶的N300 波幅，P7、P8导联的顶叶正电位波幅存在差异；而在意向提取任务中，额叶相关导联的N300 波幅，P4、P8 导联的顶叶正电位波幅存在差异。结合MRI及ERP研究提示精神分裂症PM缺陷可能源自于额顶叶功能异常，而左侧前额叶激活减弱可能是线索识别缺陷的神经基础，额极激活减弱可能是意向提取缺陷的神经基础。.该项目不仅有助于揭示精神分裂症的病理机制，而且功能康复提供新靶点，如通过针对线索识别的认知矫正治疗来治疗精神分裂症的前瞻记忆等认知缺陷症状，应用rTMS刺激左侧前额叶改善精神分裂症的线索识别能力及前瞻记忆能力，实现转化医学目的。

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