3/5 Cognitive Neuroscience Task Reliability & Clinical Applications Consortium

描述(申请人提供)：临床神经科学正处于一场革命的边缘。基于现象学的对疾病的传统概念化越来越被认为是有限的，但我们缺乏一条通向更有效方法的明确路径。研究领域标准(RDoC)倡议已经确定了一条这样的途径：检查与已知神经系统有关的行为成分，这些神经系统构成了精神病理学核心维度的基础。这一竞争性更新将提供对主要精神疾病核心症状维度潜在的认知和情感过程的新见解，并提供一套新的有效和可靠的工具，以促进RDoC和NIMH战略计划目标1.4的实现：“开发基于可观察行为和大脑功能维度的疾病分类的新方法。”该应用程序将利用CNTRaC的基础设施和专业知识来优化工作管理能力、正向和负向强化学习(包括内隐和外显)和反向学习的衡量标准，然后将它们与先前验证的衡量标准一起应用。具体目标1是验证(在精神分裂症、分裂情感障碍和双相情感障碍患者以及比较参与者中)评估我们感兴趣的六个结构的范式的优化版本，以及检查任务表现与精神病患者临床和功能结果的关系。具体目标2将评估和优化在特定目标1中验证的任务版本的重测信度和练习效果。具体目标3将使用这些优化的工作记忆容量和强化学习的测量，以及我们之前优化的WM目标保持、关系编码和提取以及视觉整合的测量，以检查在这些测量核心结构的测量上的表现与诊断(包括精神分裂症和分裂情感障碍的药物治疗和非药物治疗的个人，以及双相情感障碍患者)之间的关系。我们假设，支持WM(能力和目标维持)和关系编码/提取的背侧额叶-顶叶和额叶-颞叶系统的损害导致解体症状和功能损害，并且这些损害和关系跨越情感和非情感障碍的边界，形成一个核心维度，有助于解释各种障碍在功能和神经生物学上的重叠。我们还假设，支持强化和反向学习的眼眶额纹状体系统的损害导致快感缺失/运动障碍的负面症状，这也跨越了诊断界限。然而，我们假设快感缺失/运动障碍可能涉及初级情绪和非情绪障碍中奖赏处理和回路的不同方面，我们选择的测量方法旨在检验这一假说。我们假设，视觉整合受损，被认为反映了水平和经常性反馈的减少，将与各种障碍的无组织症状有关，但与情绪病理无关。

DESCRIPTION (provided by applicant): Clinical neuroscience is on the verge of a revolution. Traditional conceptualizations of disorders based on phenomenology are increasingly recognized as limited, but we have lacked a clear path toward a more valid approach. The Research Domain Criteria (RDoC) initiative has identified one such pathway; the examination of components of behavior linked to known neural systems that form the basis of core dimensions of psychopathology. This competing renewal will provide new insights into the cognitive and emotional processes underlying core symptom dimensions in major mental illness and provide a new set of valid and reliable tools to facilitate the aims of RDoC and Objective 1.4 of the NIMH Strategic Plan: "Develop new ways of classifying disorders based on dimensions of observable behaviors and brain functions." This application will utilize the CNTRaC's infrastructure and expertise to optimize measures of WM capacity, positive and negative reinforcement learning (both implicit and explicit) and reversal learning, and then apply them together with previously validated measures. Specific Aim 1 is to validate (in individuals with schizophrenia, schizoaffective disorder and bipolar disorder, as well as comparison participants) optimized versions of the paradigms that assess our six constructs of interest, as well as to examine the relationship of task performance to clinical and functional outcomes in psychosis. Specific Aim 2 will be to assess and optimize test-retest reliability and practice effects for the task versions validated in Specific Aim 1. Specific Aim 3 will be to use these optimized measures of working memory capacity and reinforcement learning, along with our previously optimized measures of WM goal maintenance, relational encoding and retrieval, and visual integration to examine the relationship between performance on these measures of core constructs and dimensions of psychopathology across diagnoses (including medicated and un-medicated individuals with schizophrenia and schizoaffective disorders, as well as individuals with bipolar disorder). We hypothesize that impairments in the dorsal frontal- parietal and frontal-temporal systems supporting WM (capacity and goal maintenance) and relational encoding/retrieval contribute to disorganization symptoms and functional impairment and that these impairments and relationships cut across affective and non-affective disorder boundaries, forming a core dimension that helps explain the overlap in function and neurobiology across disorders. We also hypothesize that impairments in orbital frontal-striatal systems supporting reinforcement and reversal learning contribute to the negative symptoms of anhedonia/amotivation, which also cut across diagnostic boundaries. However, we hypothesize that anhedonia/amotivation may involve different aspects of reward processing and circuitry in primary mood versus non-mood disorders with our selection of measures motivated to test this hypothesis. We hypothesize that impaired visual integration, which is thought to reflect reduced horizontal and recurrent feedback, will be related to disorganized symptoms across disorders, but will not relate to mood pathology.