Cognitive neuroscience of processing speed dysfunction in schizophrenia

精神分裂症处理速度功能障碍的认知神经科学

• 批准号: 8383333
• 负责人: Neil D. Woodward
• 金额: $ 19.5万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-04 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8383333
• 关键词: Address; Antipsychotic Agents; Area; Auditory; Behavioral; Biological Markers; Brain; Brain region; Clinical; Cognition; Cognitive; Data; Development; Dimensions; Employee Strikes; Employment; Event; Functional Imaging; Functional Magnetic Resonance Imaging; Functional disorder; Impaired cognition; Impairment; Individual; Intervention; Measures; Memory; Methods; Modality; Modeling; Motor; Motor output; Nature; Neuropsychological Tests; Outcome; Patients; Performance; Process; Production; Reaction Time; Research; Schizophrenia; Self Care; Sensory; Social Functioning; Speed; Staging; Task Performances; Testing; Training; Training Programs; Translating; Verbal Learning; Work; base; burden of illness; cognitive neuroscience; disability; effective therapy; functional outcomes; improved; information processing; meetings; neuropsychological; novel; operation; processing speed; relating to nervous system; research study; response

DESCRIPTION (provided by applicant): Processing speed is among the most impaired neuropsychological domains in schizophrenia and is strongly associated with multiple dimensions of functional outcome, including self-care management and employment. Developing effective treatments for processing speed may improve functional outcome and reduce illness burden. Unfortunately, commonly used clinical neuropsychological tests lack the precision to delineate and measure specific cognitive mechanisms contributing to processing speed impairment. This has hampered efforts to understand the neural basis of processing speed dysfunction and is a significant barrier to the development of pro-cognitive interventions. This proposal seeks to address these barriers by using cognitive neuroscience-based tasks, namely single and dual-task choice reaction time (RT) experiments, to investigate processing speed impairment in schizophrenia. Cognitive models derived from these tasks posit that information processing speed is comprised of 3 stages: perceptual analysis, response selection, and response production. The available evidence from the handful of studies employing these paradigms suggests that response selection is differentially impaired in schizophrenia. However, it is not known if the impairment results from dysfunction of a unitary response selection process that cuts across sensory and motor modalities, or is modality specific. Resolving this issue is crucial to understanding the neural basis and treatment of the deficit. Generalized impairment would implicate dysfunction of a central, amodal response selection network and indicate that training programs shown to improve response selection and the speed of neural processing in amodal response selection brain regions should be attempted in schizophrenia. Conversely, modality-specific impairment would implicate dysfunction of modality-specific neural machinery and suggest that interventions targeting specific sensory and/or motor processes might be more effective at improving processing speed in schizophrenia. Evidence that auditory training improves verbal learning and memory provides a striking demonstration of a modality-specific approach to improving cognition in schizophrenia. The specific aims of this proposal are: 1) test the hypothesis that response selection impairment in schizophrenia generalizes across sensory and motor modalities; and 2) examine the integrity of multi-modal response selection brain networks and modality-specific brain regions in schizophrenia. The anticipated results of this work will further our understanding of the specific cognitive operations contributing to slowed processing speed in schizophrenia, identify candidate biomarkers of processing speed dysfunction, and lend guidance to the development and selection of pro-cognitive interventions. PUBLIC HEALTH RELEVANCE: Cognitive impairment in schizophrenia leads to profound disability and is a robust predictor of multiple dimensions of outcome, including self-care management, social functioning, and employment. This proposal will use cognitive neuroscience based methods to better understand the nature and neural basis of cognitive impairment in schizophrenia. The results of this work will help guide the selection of existing therapies to improving cognition and facilitate the development of novel pharmacological and non-pharmacological pro-cognitive interventions.

描述（由申请人提供）：处理速度是精神分裂症中最受损的神经心理领域之一，并且与功能结果的多个维度密切相关，包括自我护理管理和就业。开发有效的处理速度治疗方法可以改善功能结果并减轻疾病负担。不幸的是，常用的临床神经心理学测试缺乏描述和测量导致加工速度损害的特定认知机制的精确度。这阻碍了理解处理速度功能障碍的神经基础的努力，并且是对认知干预措施发展的重要障碍。该建议旨在通过使用基于认知神经科学的任务，即单一和双任务选择反应时间（RT）实验来解决这些障碍，以研究精神分裂症的加工速度损害。从这些任务中得出的认知模型认为，信息处理速度由3个阶段组成：感知分析，响应选择和响应产生。使用这些范式的少数研究的可用证据表明，精神分裂症中的反应选择差异受损。但是，尚不清楚损害是否是由于跨感觉和运动方式切割的单一响应选择过程的功能障碍而导致的，还是特定于模态。解决这个问题对于理解赤字的神经基础和治疗至关重要。普遍的损害将暗示中央，Amodal响应选择网络的功能障碍，并表明在精神分裂症中应尝试尝试改善旨在改善响应选择的训练计划和Amodal反应选择大脑区域中的神经处理速度。相反，特定于模态的损害将暗示对模式特异性神经机械的功能障碍，并表明针对特定感觉和/或运动过程的干预措施在提高精神分裂症的加工速度方面可能更有效。听觉训练改善言语学习和记忆的证据为改善精神分裂症认知的方式提供了惊人的证明。该提案的具体目的是：1）检验以下假设：精神分裂症中的反应选择障碍在感觉和运动方式上概括了； 2）检查精神分裂症中多模式反应选择大脑网络和模式特异性大脑区域的完整性。这项工作的预期结果将进一步了解我们对精神分裂症加工速度降低的特定认知操作的理解，确定候选速度功能障碍的候选生物标志物，并为促进认知干预措施的发展和选择提供指导。 公共卫生相关性：精神分裂症的认知障碍会导致严重的残疾，并且是对结果多个维度的强大预测指标，包括自我保健管理，社会功能和就业。该建议将使用基于认知神经科学的方法来更好地了解精神分裂症认知障碍的性质和神经基础。这项工作的结果将有助于指导选择现有疗法，以改善认知并促进新型药理和非药理学亲认知干预措施的发展。