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。基于现象学的传统疾病概念化越来越被认为是有限的，但我们缺乏通往更有效方法的明确途径。研究领域标准（RDoC）倡议已经确定了一条这样的途径；对与构成精神病理学核心维度基础的已知神经系统相关的行为成分的检查。这种竞争性的更新将为主要精神疾病的核心症状维度的认知和情感过程提供新的见解，并提供一套新的有效可靠的工具，以促进RDoC的目标和NIMH战略计划的目标1.4：“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WM容量、正强化和负强化学习（隐式和显式）和反转学习的测量，然后将它们与先前验证的测量一起应用。具体目标1是验证（在患有精神分裂症、分裂情感障碍和双相情感障碍的个体中，以及比较参与者中）评估我们感兴趣的六个构念的范式的优化版本，并检查任务表现与精神病临床和功能结果的关系。具体目标2将评估和优化在具体目标1中验证的任务版本的重测信度和实践效果。具体目标3将是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目标维持，关系编码和检索以及视觉整合的测量来检查这些核心构念测量的表现与跨诊断的精神病理学维度之间的关系（包括患有精神分裂症和分裂情感障碍的药物和未药物治疗的个体）。以及双相情感障碍患者)。我们假设，支持WM（能力和目标维持）和关系编码/检索的背额顶叶和额颞叶系统的损伤有助于紊乱症状和功能损伤，这些损伤和关系跨越了情感和非情感障碍的界限，形成了一个核心维度，有助于解释跨障碍的功能和神经生物学重叠。我们还假设支持强化和反向学习的眶额纹状体系统的损伤有助于快感缺乏/动机的负面症状，这也跨越了诊断界限。然而，我们假设快感缺乏症/动机可能涉及初级情绪障碍与非情绪障碍的奖励处理和回路的不同方面，并通过我们选择的措施来验证这一假设。我们假设受损的视觉整合，被认为反映了水平反馈和反复反馈的减少，将与跨障碍的紊乱症状有关，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.