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治疗方法可以改善功能预后并减轻疾病负担。不幸的是，常用的临床神经心理学测试在描述和测量导致处理速度损伤的特定认知机制方面缺乏精确性。这阻碍了理解处理速度功能障碍的神经基础的努力，并且是促进认知干预发展的重大障碍。本研究旨在通过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，来研究精神分裂症的加工速度损伤，从而解决这些障碍。从这些任务中衍生出的认知模型假设信息处理速度由三个阶段组成：感知分析、反应选择和反应产生。从采用这些范式的少数研究中获得的证据表明，精神分裂症患者的反应选择受到了不同程度的损害。然而，目前尚不清楚这种损伤是由跨越感觉和运动模式的单一反应选择过程的功能障碍引起的，还是由特定模式引起的。解决这个问题对于理解神经基础和治疗缺陷至关重要。广泛性损伤可能涉及中枢、模态反应选择网络的功能障碍，并表明应在精神分裂症中尝试训练项目，以提高反应选择和模态反应选择脑区域的神经处理速度。相反，模式特异性损伤可能涉及模式特异性神经机制的功能障碍，并表明针对特定感觉和/或运动过程的干预可能更有效地提高精神分裂症的处理速度。听觉训练提高语言学习和记忆的证据，为改善精神分裂症患者的认知提供了一种模式特异性方法的惊人证明。本研究的具体目的是：1)检验精神分裂症患者反应选择障碍在感觉和运动模式中普遍存在的假设；2)研究精神分裂症患者多模态反应选择脑网络和模态特异性脑区域的完整性。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处理速度减慢的特定认知操作的理解，确定处理速度功能障碍的候选生物标志物，并为开发和选择促进认知干预措施提供指导。

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.