Cognitive neuroscience of processing speed dysfunction in schizophrenia

描述(由申请人提供)：处理速度是精神分裂症患者中受损最严重的神经心理领域之一，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的治疗方法可能会改善功能结果，减轻疾病负担。不幸的是，常用的临床神经心理学测试缺乏对导致加工速度障碍的特定认知机制的描述和测量的精确度。这阻碍了理解加工速度障碍的神经基础的努力，也是发展前认知干预的重大障碍。这项建议试图通过使用基于认知神经科学的任务，即单任务和双任务选择反应时间(RT)实验来解决这些障碍，以调查精神分裂症患者的加工速度障碍。这些任务的认知模型假设信息处理速度由三个阶段组成：知觉分析、反应选择和反应产生。少数使用这些范式的研究提供的证据表明，精神分裂症患者的反应选择受到不同程度的损害。然而，目前尚不清楚这种损害是由于横跨感觉和运动通道的单一反应选择过程的功能障碍所致，还是与通道有关。解决这一问题对于理解缺陷的神经基础和治疗至关重要。全身性损伤会导致中枢非传导性反应选择网络的功能障碍，并表明在精神分裂症患者中应该尝试训练计划，以改善反应选择和非传导性反应选择脑区的神经处理速度。相反，特定通道的损伤会导致特定通道神经机械的功能障碍，并表明针对特定感觉和/或运动过程的干预可能在提高精神分裂症的处理速度方面更有效。听觉训练改善言语学习和记忆的证据为改善精神分裂症患者认知的特定通道方法提供了一个引人注目的例证。这项建议的具体目的是：1)检验精神分裂症反应选择障碍在感觉和运动模式中普遍存在的假设；2)检查精神分裂症患者多模式反应选择脑网络和特定模式脑区的完整性。这项工作的预期结果将进一步加深我们对导致精神分裂症加工速度减慢的特定认知操作的理解，识别加工速度障碍的候选生物标志物，并为促进认知干预的开发和选择提供指导。

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.