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学领域之一，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以改善功能结果并减少疾病负担。不幸的是，常用的临床神经心理学测试缺乏精确性来描绘和测量有助于处理速度障碍的特定认知机制。这阻碍了理解处理速度功能障碍的神经基础的努力，并且是促认知干预发展的重大障碍。该建议旨在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（RT）实验，来研究精神分裂症的加工速度障碍，以解决这些障碍。由这些任务衍生出的认知模型认为，信息加工速度由知觉分析、反应选择和反应产生三个阶段组成。现有的证据，从少数研究采用这些范式表明，反应选择是差异受损的精神分裂症。然而，目前尚不清楚这种损伤是否是由跨越感觉和运动模态的单一反应选择过程的功能障碍引起的，或者是模态特异性的。解决这个问题对于理解神经基础和治疗缺陷至关重要。广义的损害将牵连功能障碍的一个中央，非模态反应选择网络，并表明训练计划，以改善反应选择和神经处理速度的非模态反应选择脑区应尝试在精神分裂症。相反，模态特异性损伤将涉及模态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改善精神分裂症的处理速度。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特定模态方法提供了一个引人注目的证明。该提案的具体目的是：1）测试精神分裂症中的反应选择障碍在感觉和运动模态中普遍存在的假设; 2）检查精神分裂症中多模态反应选择脑网络和模态特定脑区的完整性。这项工作的预期结果将进一步促进我们对精神分裂症中导致加工速度减慢的特定认知操作的理解，确定加工速度功能障碍的候选生物标志物，并为开发和选择促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.