Functional Magnetic Resonance Studies in Schizophrenia

描述：（由申请人提供）主要的长期职业目标 研究者的目的是增进对精神分裂症相关功能的了解 通过建立和指导脑成像实验室来研究神经病理学。的 短期目标是发展设计、执行和 使用一系列功能磁共振成像 (fMRI) 研究进行分析 扫视任务。这些目标的实现将通过 强化培训与完成系统研究相结合 在拟议的资助期内制定计划。 功能神经影像培训将在 UCSD 功能中心内进行 神经影像组以及 NIMH 每年为期两周的培训课程。 神经解剖学和神经心理学培训将在加州大学圣地亚哥分校内完成 神经科学界。该研究计划利用了 P.I. 的现有研究 精神分裂症患者及其亲属的眼跳表现 生成和检验基本假设的基础 与精神分裂症相关的神经节-丘脑皮质回路功能障碍。 精神分裂症患者在再注视扫视任务中表现正常，但是 表现出抗眼跳和眼球运动的特征性异常 延迟响应任务。观察到类似的表现模式 患者的生物学亲属，表明这种表型可能是 与发展为精神分裂症的责任有关。图案为 扫视表现与前额皮质及其病理学一致 相关的皮质和/或皮质下电路。这个假设可能会被检验 在功能磁共振成像期间使用扫视任务作为行为探针来测量 BOLD（血液 受试者参与时的信号变化取决于氧合水平 持续的行为和认知活动。 提出了三个具体目标； 1）评估神经激活模式 与精神分裂症和正常人的再注视扫视表现相关 受试者，2）测试不同额叶激活模式的假设 在表面上需要的任务期间，精神分裂症患者和正常人群之间的差异 前额介导的抑制（反眼跳和延迟反应任务），以及 3）测试生物中前额皮质功能障碍的假设 精神分裂症患者的亲属。

DESCRIPTION: (provided by applicant) The long-term career goal of the primary investigator is to advance the knowledge ot schizophrenia-related functional neuropathology by establishing and directing a brain imaging laboratory. The short-term goal is to develop an expertise in the design, execution, and analysis of functional magnetic resonance imaging (fMRI) studies using a series of saccadic tasks. The realization of these goals will occur through a combination of intensive training and the completion of a systematic research plan over the course of the proposed funding period. Training in functional neuroimaging will occur within the UCSD functional neuroimaging group and during yearly 2-week training sessions at the NIMH. Training in neuroanatomy and neuropsychology will be completed within the UCSD neuroscience community. The research plan utilizes the P.I.'s existing studies on the saccadic performance of schizophrenia patients and their relatives as a foundation for generating and testing hypotheses of basal ganglia-thalamocortical circuitry dysfunction associated with schizophrenia. Schizophrenia patients perform normally on refixation saccade tasks, but demonstrate characteristic abnormalities on antisaccade and ocular motor delayed response tasks. A similar pattern of performance is observed among biological relatives of the patients, suggesting that this phenotype may be associated with the liability for developing schizophrenia. The pattern of saccadic performance is consistent with pathology of prefrontal cortex and its associated cortical and/or subcortical circuitry. This hypothesis may be tested using saccadic tasks as behavioral probes during fMRI to measure BOLD (blood oxygenation level dependent) signal change while subjects are engaged in ongoing behavioral and cognitive activity. Three specific aims are proposed; 1) evaluate the patterns of neural activation associated with refixation saccade performance in schizophrenia and normal subjects, 2) to test hypotheses of differing patterns of frontal activation between schizophrenia and normal groups during tasks that ostensibly require prefrontally-mediated inhibition (antisaccade and delayed response tasks), and 3) to test hypotheses of prefrontal cortex dysfunction among the biological relatives of schizophrenia patients.