Neuroimaging and Neurocognitive Computerized Adaptive Testing in Schizophrenia

描述(申请人提供)：尽管精神分裂症研究人员在临床研究中识别心理测量混淆方面有丰富的历史，但问题仍然困扰着该领域的一些领域，因为这些混淆已经通过20世纪初开发的测量技术得到解决。例如，在功能磁共振成像(FMRI)中，通过扫描过程中使用的工作记忆(WM)任务引发的大脑激活和行为之间的联系可能会被传统测量技术产生的混乱所掩盖。这笔拨款的中心前提是，将现代测量理论应用于任务开发，对于使用功能磁共振成像测试认知精神病理学的高级大脑行为模型至关重要。因此，该项目将侧重于心理成像方面的培训和研究。该奖项将为候选人提供支持，以追求职业发展目标，以补充他在先进测量理论和技术方面的专业知识，以及以精神分裂症为应用重点的功能磁共振培训。第一个培训目标是让候选人获得进行精神分裂症研究所需的知识和技能。在具体目标1中，他将利用这项培训来证明，通过神经认知计算机化的适应性测试，将项目难度与工作记忆能力相匹配，将患者和对照组之间的能力估计标准误差降至最低并相等。这一目标将建立一种创新的方法，以消除精神分裂症研究中存在的差异可靠性混乱。第二个培训目标是让候选人获得进行功能磁共振研究所需的知识和技能。在特定的目标2中，他将利用这项培训来比较精神分裂症患者和对照组参与者背侧前额叶皮质的血氧水平依赖反应，以测试精神分裂症患者WM缺陷的倒置U形和神经低效脑激活模型。这一目标将正式检验认知精神病理学中两种广泛假设但未经证实的理论。第三个培训目标是培养研究功能性麦片网络所需的分析技能。在具体目标3中，他将利用这种训练，使用状态空间建模来绘制fMRI数据中的时空激活模式，以探索患者比对照组表现出更多无序的神经招募的理论。这一目标将有力地检验大脑行为理论，该理论假设精神分裂症患者的WM缺陷与神经招募的不良组织模式有关--表现为大脑状态的增加以及与表现脱钩的激活--使用定义明确的现代心理测量方法。候选人的长期目标是为研究精神分裂症和其他基于大脑的疾病的研究人员提供心理成像咨询，并制定一项R01计划，研究高级神经成像和精神障碍认知精神病理学的数学模型。这一系列研究将通过确定潜在的神经靶点来为精神病治疗做出贡献，旨在减少精神病患者的神经认知缺陷。

DESCRIPTION (provided by applicant): Although schizophrenia researchers have a rich history of identifying psychometric confounds in clinical studies, problems continue to plague some areas of the field because these confounds have been addressed using measurement technologies developed in the early 20th century. In functional magnetic resonance imaging (fMRI), for instance, links between brain activation and behavior elicited through working memory (WM) tasks used during scanning can be obscured by confounds stemming from traditional measurement technology. The central premise of this grant is that applying modern measurement theory to task development is critical for using fMRI to test advanced brain-behavior models of cognitive psychopathology. Accordingly, this project will focus on training and research in psychometric imaging. The award will provide the candidate with support to pursue career development objectives that complement his expertise in advanced measurement theory and technology with training in fMRI with an applied focus on schizophrenia. The first training objective is for the candidate to obtain knowledge and skills needed to conduct schizophrenia research. In Specific Aim 1 he will use this training to show that matching item difficulty to WM ability through neurocognitive computerized adaptive testing minimizes and equates standard errors of ability estimates between patients and controls. This aim will establish an innovative methodology for eliminating the differential reliability confound in schizophrenia research. The second training objective is for the candidate to obtain knowledge and skills needed to conduct fMRI research. In Specific Aim 2 he will use this training to compare blood oxygen level-dependent response in dorsolateral prefrontal cortex between schizophrenia and control participants in order to test inverted-"U" and neural inefficiency brain activation models of WM deficits in schizophrenia. This aim will formally test two widely assumed but unconfirmed theories of cognitive psychopathology in the disorder. The third training objective is for the candidate to develop analytical skills needed to study functional bran networks. In Specific Aim 3 he will use this training to map spatiotemporal activation patterns in fMRI data using state-space modeling in order to explore the theory that patients show more disorganized neural recruitment than controls. This aim will robustly test the brain-behavior theory positing that WM deficits in schizophrenia are associated with poorly organized patterns of neural recruitment-as manifested by an increased number of brain-states and by activation that is uncoupled from performance-using a well-defined and modern psychometric testing approach. The candidate's long-term goals are to provide psychometric imaging consultation to researchers studying schizophrenia and other brain-based disorders and to develop an R01 plan to study advanced neuroimaging and mathematical modeling of cognitive psychopathology in psychotic disorders. This line of research will contribute to public health by identifying potential neural targets for psychiatric treatments aimed at reducing neurocognitive deficits in psychosis.