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Neural mechanisms of perceptual organization deficits across the schizo-bipolar spectrum

精神分裂-双相情感障碍中知觉组织缺陷的神经机制

基本信息

批准号：
9762178
负责人：
Brian Patrick Keane
金额：
$ 17万
依托单位：
RUTGERS BIOMEDICAL/HEALTH SCIENCES-RBHS
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-01 至 2021-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9762178
关键词：
Address Adult Area Award Behavioral Biological Markers Bipolar Disorder Brain Brain imaging Categories Chronic Schizophrenia Clinical Clinical Sciences Complex Conceptions Data Data Collection Diagnosis Diagnostic Dimensions Disease Elements Enrollment Environment Exhibits Experimental Designs Exposure to Eye Movements Faculty Feedback Functional Imaging Functional Magnetic Resonance Imaging Functional disorder Funding Future Genetic Predisposition to Disease Goals Health Personnel Healthcare Illusions Imaging Techniques Impairment Individual Infrastructure Investigation Knowledge Lateral Learning Length of Stay Literature Measures Mental Health Mental disorders Mentorship Methodology Methods Molecular Moods National Institute of Mental Health Nature Neuroanatomy Neurobiology Neurosciences Outcome Patients Pattern Phase Population Process Psychology Psychopathology Psychopharmacology Psychophysics Psychotic Disorders Publishing Recording of previous events Research Research Domain Criteria Research Training Risk Role Running Schizophrenia Shapes Stage Grouping Structure Students Symptoms Testing Time Training United States Universities Vision Vision research Visual Visual Cortex behavioral health bipolar spectrum brain behavior career cognitive neuroscience experimental analysis functional decline functional disability gray matter improved insight interest movement analysis neuroimaging neuromechanism object perception patient subsets perceptual organization professor relating to nervous system retinal imaging severe mental illness spatiotemporal success tool visual information visual neuroscience visual processing

项目摘要

Project Summary/Abstract [public] Candidate's short and long-term goals. The candidate's ultimate career goal is to become a tenured university professor who explores aspects of visual object perception using clinical science, neuroscience, and behavioral psychophysics. Overarching questions central to the research include: How does the brain construct and maintain coherent object representations despite a spatiotemporally fragmented retinal image? How do these integration processes break down when the brain is afflicted with serious mental illness? And what can we learn about mental disorders by looking at these processes? During the award period, four knowledge areas will be developed or deepened so as to increase the chances of long-term career success. First, basic methods in fMRI experimental design and analysis will be acquired such as functional connectivity and ROI analyses. A second goal is to develop expertise in basic neuroscience, including psychopharmacology and functional neuroanatomy. A third goal will be to improve knowledge of psychopathology, especially in regards to bipolar disorder. A final objective is to gain exposure to recent methods in vision and visual neuroscience such as eye movement analyses or neurostimulation. Training environment. A major component of the research and training will take place at the Center for Molecular and Behavioral Neuroscience (CMBN) on the Newark campus of Rutgers, which includes the Rutgers University Brain Imaging Center (RUBIC). The candidate has had hardly any exposure to faculty, staff or research on the Newark campus and is just at the very beginning of learning fMRI. Therefore, the activities at CMBN and Rutgers—Newark Psychology will provide exposure to new professors, new students, and new methodologies in cognitive neuroscience, underscoring the training potential of this application. Moreover, Rutgers University Behavioral Health Care (UBHC) is one of the largest academically-affiliated mental health providers in the United States, offering ample opportunity to find willing patients with schizophrenia or bipolar disorder. The infrastructure for finding and running patients at Rutgers has been intact for many years, indicating that rapid progress on the proposed research can be expected. The co-sponsors, as a group, are well-published, well-funded, have a history of mentorship, and have overlapping interests with my own. The union of their areas of expertise span vision research, cognitive neuroscience, fMRI, and psychopathology, which correspond to the four training areas identified above. Description of research. Perceptual organization (PO) refers to the ability to represent spatially segregated elements as unified wholes or inter-related parts. Numerous studies suggest that people with schizophrenia (SZ) are impaired at PO, but the neural mechanisms and clinical implications of the impairment are just beginning to be explored. Addressing this issue is valuable because PO deficits arise as early as the prodromal or first episode stages in SZ, and because they at times predict more severe disorganization and functional disability. To gain insight into the neural basis and diagnostic scope of PO deficits, a two-phase fMRI investigation will be conducted. In the first phase, the aim is to understand the neural basis for why PO deficits arise in SZ (Aim 1). Recent studies have suggested that PO deficits originate in early visual cortex, perhaps because of impaired lateral connectivity in this area. At the same time, SZ is characterized by prefrontal cortical dysfunction, and this has recently been shown to be relevant for perceptual organization. To determine whether prefrontal cortical contributions best explain PO deficits in SZ, I will learn recent functional imaging techniques—including functional connectivity, ROI, and multivariate pattern analyses—to compare SZ patients and matched healthy controls on three PO tasks. If PO dysfunction arises even at the earliest visual grouping stages, then this would broaden our conception of SZ and support prior studies that argue for integrative abnormalities in V1/V2. By contrast, if PO dysfunction arises only at late stages over prefrontal cortical areas, then that would give a new interpretation of previous studies, and add to the growing evidence for prefrontal cortical dysfunction in SZ. Regardless of the outcome, new insights will be had about the underlying pathophysiology of SZ, fulfilling NIMH Strategy 1.1. In the second phase of the study, it will be examined to what extent PO deficits arise in bipolar disorder, which shares a common genetic etiology with SZ (Aim 2). There are very few PO studies of bipolar disorder, and perhaps none that have used fMRI. Therefore, this investigation will provide entirely new insights into the nature and perceptual consequences of this related illness, fulfilling again NIMH Strategy 1.1. Once data collection ends, patient data will be combined across phases to assess whether the behavioral and neural signatures of PO co-vary with other clinical variables across disorders, such as levels of functioning, and conceptual disorganization (Aim 3). The investigation will clarify whether previously documented PO abnormalities in SZ are best attributed to diagnostic category or symptom dimensions (psychotic/mood), a question that is deemed high priority by the NIMH Strategy 1.4 (RDoC Initiative). It will also examine whether there are patient subgroups that exhibit similar degrees of perceptual dysfunction but that do not share a diagnosis. In summary, the three aims achieved over two data collection phases will elucidate the neural mechanisms and clinical implications of PO dysfunction across the schizo-bipolar spectrum.

项目摘要/摘要[公开] 候选人的短期和长期目标。候选人的最终职业目标是成为终身教授大学教授，利用临床科学、神经科学和行为心理物理学。该研究的核心问题包括：大脑如何尽管视网膜图像时空碎片，仍能构建并保持连贯的对象表示？当大脑患有严重的精神疾病时，这些整合过程是如何崩溃的？和通过观察这些过程，我们可以了解有关精神障碍的哪些信息？颁奖期间，四知识领域将得到发展或深化，以增加长期职业成功的机会。首先，掌握功能连接等功能磁共振实验设计和分析的基本方法和投资回报率分析。第二个目标是发展基础神经科学的专业知识，包括精神药理学和功能神经解剖学。第三个目标是提高对以下方面的认识：精神病理学，特别是双相情感障碍。最终目标是接触最近的视觉和视觉神经科学中的方法，例如眼动分析或神经刺激。训练环境。研究和培训的主要部分将在该中心进行罗格斯大学纽瓦克校区的分子与行为神经科学 (CMBN)，其中包括罗格斯大学脑成像中心 (RUBIC)。候选人几乎没有接触过教职员工或在纽瓦克校区进行研究，并且刚刚开始学习功能磁共振成像。因此，活动在 CMBN 和罗格斯大学 - 纽瓦克心理学中心将提供接触新教授、新学生和新知识的机会认知神经科学的方法论，强调了该应用程序的训练潜力。而且，罗格斯大学行为健康护理 (UBHC) 是最大的学术附属心理健康机构之一美国的医疗服务提供者提供充足的机会寻找愿意的精神分裂症或双相情感障碍患者紊乱。罗格斯大学用于寻找和治疗患者的基础设施多年来一直完好无损，表明拟议的研究有望取得快速进展。作为一个团体，共同发起者是出版良好，资金充足，有指导历史，并且与我自己的兴趣有重叠。这他们的专业领域涵盖视觉研究、认知神经科学、功能磁共振成像和精神病理学，对应于上述四个培训领域。研究描述。感知组织（PO）是指表示空间隔离的能力元素作为统一的整体或相互关联的部分。大量研究表明，精神分裂症患者 (SZ) 在 PO 时受损，但该受损的神经机制和临床意义只是开始被探索。解决这个问题很有价值，因为 PO 赤字早在 SZ 的前驱期或首发阶段，因为它们有时预示着更严重的混乱和功能障碍。为了深入了解 PO 缺陷的神经基础和诊断范围，两相功能磁共振成像 (fMRI) 将进行调查。第一阶段的目标是了解 PO 缺乏的神经基础出现在深圳（目标 1）。最近的研究表明 PO 缺陷可能起源于早期视觉皮层因为该区域的横向连通性受损。同时，SZ的特点是前额叶皮质功能障碍，最近被证明与知觉组织有关。确定前额皮质的贡献是否最能解释 SZ 的 PO 缺陷，我将学习最近的功能成像技术（包括功能连接、ROI 和多变量模式分析）来比较 SZ 患者并在三项 PO 任务上匹配健康对照。即使在最早的视觉分组时也会出现 PO 功能障碍阶段，那么这将拓宽我们对 SZ 的概念，并支持先前主张整合的研究 V1/V2 异常。相比之下，如果 PO 功能障碍仅在前额皮质区域的晚期出现，那么这将为之前的研究提供新的解释，并为前额叶的不断增加的证据提供支持 SZ 的皮质功能障碍。无论结果如何，都会对潜在的问题有新的见解 SZ 的病理生理学，履行 NIMH 策略 1.1。在研究的第二阶段，将检查双相情感障碍中 PO 缺陷的程度如何，双相情感障碍与 SZ 具有共同的遗传病因（目标 2）。关于双相情感障碍的 PO 研究很少，也许没有使用功能磁共振成像的研究。因此，这调查将为这种相关的性质和感知后果提供全新的见解疾病，再次履行 NIMH 策略 1.1。数据收集结束后，患者数据将被合并评估 PO 的行为和神经特征是否与其他临床变量共同变化的阶段跨越障碍，例如功能水平和概念混乱（目标 3）。调查将澄清之前在 SZ 记录的 PO 异常是否最好归因于诊断类别或症状维度（精神病/情绪），NIMH 策略 1.4 认为该问题高度优先（RDoC 倡议）。它还将检查是否存在表现出相似程度的患者亚组知觉功能障碍，但不具有共同的诊断。综上所述，通过两个数据实现了三个目标收集阶段将阐明 PO 功能障碍的神经机制和临床意义精神分裂双极谱。