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

• 批准号: 9544318
• 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
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9544318
• 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; 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 Infrastructure; 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

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[公共] 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职 大学教授，利用临床科学、神经科学和科学探索视觉物体感知的各个方面 行为心理物理学。这项研究的核心问题包括：大脑是如何 构建和维护连贯的对象表示，尽管视网膜图像在时空上是零散的？ 当大脑受到严重精神疾病的困扰时，这些整合过程是如何中断的？和 通过观察这些过程，我们可以了解到精神障碍的哪些方面？在颁奖期间，有四名 将开发或深化知识领域，以增加长期职业成功的机会。 首先，掌握fMRI实验设计和分析的基本方法，如功能连通性 和ROI分析。第二个目标是发展基础神经科学方面的专业知识，包括 精神药理学和功能神经解剖学。第三个目标将是提高对 精神病理学，尤指有关双相情感障碍的。最后一个目标是接触到最近的 视觉和视觉神经科学中的方法，如眼动分析或神经刺激。 训练环境。研究和培训的一个主要部分将在中心进行 位于罗格斯大学纽瓦克校区的分子和行为神经科学(CMBN)，包括 罗格斯大学脑成像中心(RUBIC)。这位候选人几乎没有接触过教职员工 或在纽瓦克校园进行研究，而学习功能磁共振才刚刚开始。因此，这些活动 在CMBN和罗格斯-纽瓦克，心理学将提供对新教授、新学生和新 认知神经科学的方法论，强调这一应用的培训潜力。此外， 罗格斯大学行为健康护理(UBHC)是最大的学术附属精神健康之一 在美国提供服务，提供充足的机会寻找自愿的精神分裂症或躁郁症患者 无序。罗格斯大学寻找和管理病人的基础设施多年来一直完好无损， 这表明，可以预期拟议的研究将迅速取得进展。共同发起人，作为一个团体，是 发表得很好，资金充裕，有导师的历史，和我自己的兴趣有重叠。这个 他们的专业领域包括视觉研究、认知神经科学、功能磁共振成像和精神病理学， 它们对应于上文确定的四个培训领域。 研究的描述。感知组织(PO)指的是表现空间隔离的能力 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，但这种损害的神经机制和临床意义只是 开始被探索。解决这一问题很有价值，因为采购订单赤字早在 SZ的前驱或首发阶段，因为它们有时预示着更严重的组织紊乱和 功能性残疾。为了深入了解PO缺陷的神经基础和诊断范围，进行了双期fMRI 将进行调查。在第一阶段，目的是了解PO赤字的神经基础 在深圳崛起(目标1)。最近的研究表明，PO缺陷可能起源于早期的视觉皮质 因为这一区域的横向连通性受损。同时，SZ还具有前锋的特征 皮质功能障碍，最近被证明与知觉组织有关。要确定 前额叶皮质贡献是否能最好地解释深圳的PO缺陷，我将学习最近的功能成像 比较SZ患者的技术--包括功能连通性、ROI和多变量模式分析 并在三个PO任务上与健康对照组相匹配。如果即使在最早的视觉分组时也出现PO功能障碍 阶段，那么这将拓宽我们对SZ的概念，并支持先前关于一体化的研究 V1/V2异常。相反，如果PO功能障碍仅出现在前额叶皮质区域的晚期， 这将对以前的研究给予新的解释，并增加越来越多的前额叶证据。 深圳地区的皮质功能障碍。无论结果如何，都将对潜在的问题有新的见解 SZ的病理生理学，满足NIMH策略1.1。在第二阶段的研究中，将研究 在双相情感障碍中出现PO缺陷的程度，这与SZ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，也许还没有使用过功能磁共振成像的研究。因此，这 调查将为与此相关的性质和感知后果提供全新的见解 疾病，再次实现NIMH战略1.1。数据收集结束后，患者数据将跨 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 跨障碍，如功能水平和概念上的混乱(目标3)。调查将会进行 澄清以前记录的深圳PO异常最好归因于诊断类别还是 症状维度(精神病/情绪)，NIMH战略1.4认为这是一个高度优先的问题 (RDoC倡议)。它还将检查是否有患者亚组表现出类似程度的 知觉功能障碍，但这不是一个共同的诊断。总而言之，这三个目标实现了两个以上的数据 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-双相情感谱系。