Spatial frequency contributions to contour integration deficits in schizophrenia

空间频率对精神分裂症轮廓整合缺陷的贡献

• 批准号: 8256062
• 负责人: Brian Patrick Keane
• 金额: $ 5.29万
• 依托单位: UNIV OF MED/DENT NJ-R W JOHNSON MED SCH
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8256062
• 关键词: Accounting; Address; Age; Animals; Biological Markers; Brain; Clinical; Control Groups; Data; Data Collection; Development; Discrimination; Disease; Drops; Electroencephalography; Elements; Evaluation; Frequencies; Functional Magnetic Resonance Imaging; Functional disorder; Future; Gender; Impairment; Indium; Investigation; Lateral; Length of Stay; Light; Link; Literature; Longitudinal Studies; Measures; Mental disorders; Methods; National Institute of Mental Health; Ocular orbit; Patients; Performance; Phase; Process; Property; Psychophysiology; Recruitment Activity; Research; Schizophrenia; Shapes; Social Functioning; Stimulus; Stream; Structure; Symptoms; Testing; Time; Visual Cortex; base; brain behavior; experience; first episode psychosis; functional decline; functional outcomes; gray matter; luminance; magnocellular; neuromechanism; object shape; perceptual organization; relating to nervous system; response; stem

DESCRIPTION (provided by applicant): Contour integration (CI)-for the purposes of the present application-refers to the ability to represent spatially segregated edges as a single continuous contour. Numerous studies suggest that people with schizophrenia (SZ) are impaired at contour integration, but the mechanisms, time-course, and clinical implications of the impairment are just beginning to be explored. To shed light on this issue, we conduct a two phase psychophysical investigation. In the first phase, we will satisfy NIMH Strategy 1.1, and clarify the neural mechanisms behind the deficit (Aim 1). Clinical CI studies to date have almost exclusively employed lower spatial frequency contour elements (<7 cycles/deg), but converging evidence suggests that schizophrenia is characterized by magnocellular dysfunction and, correspondingly, impaired processing of lower spatial frequencies (<8 cycles deg). To determine whether spatial frequency processing can account for CI deficits in SZ, a later-episode patient group and a matched healthy control group will perform 4 different tasks. The spatial frequency structure of the stimuli for each task will be varied to either include or not include low spatial frequencies. If CI deficits arise even with elements defined by high spatial frequencies, then impaired lateral interactions in early visual cortex would be evidenced as a core feature of schizophrenia. By contrast, if CI dysfunction arises only when lower spatial frequencies are available, then that would add to the growing evidence for magnocellular dysfunction in SZ, and would provide a new interpretation of results stemming from CI tasks. In the second data collection phase, we will satisfy NIMH Strategy 2.1 and examine the development of CI deficits from first-episode onward (Aim 2). Newly recruited subjects will be either healthy controls, first- episode patients, or later-episode patients. The tasks in this second phase will be the same as those that revealed between-group differences (p<0.05) in the first phase. Importantly, this phase will provide the first data on whether CI deficits exist among people with schizophrenia who recently experienced their first psychotic episode. At the end of data collection, we will combine data across phases to make two determinations. First, we will assess if CI deficits-at either high or lower spatial frequencies- correlate with clinical variables such as: functional outcome, disorganized symptoms, positive/negative symptoms, and premorbid social functioning (Aim 3). Second, we will compare the four tasks on the basis of: between-group effect sizes, capacities to predict illness features, total duration, and drop-out rate (Aim 4). Evaluating the tasks in this way will guide future larger-scale studies aiming to further establish, explain, or make use of contour deficits in schizophrenia. In summary, the four aims achieved over two data collection phases will elucidate the neural mechanisms, time course, clinical correlates, and optimal measures of contour integration dysfunction in schizophrenia. PUBLIC HEALTH RELEVANCE: In accord with NIMH Strategy 1.1 ("Develop an integrative understanding of basic brain-behavior processes...for understanding mental illness"), the proposed research will clarify the brain mechanisms that underlie the reduced ability to connect spatially separated contour elements in schizophrenia. Furthermore, consistent with NIMH Strategy 2.1 ("Define the developmental trajectories of mental disorders"), the proposed research will describe the developmental trajectory of perceptual dysfunction in schizophrenia, and provide the first substantive data on whether contour integration impairments are present as early as the first episode of psychosis.

描述（由申请人提供）：轮廓集成（CI） - 用于本应用程序的目的，以将空间隔离边缘表示为单个连续轮廓的能力。大量研究表明，精神分裂症（SZ）的人在轮廓整合中受到损害，但是刚刚开始探索损害的机制，时间课和临床意义。为了阐明这个问题，我们进行了两阶段的心理物理研究。在第一阶段，我们将满足NIMH策略1.1，并阐明赤字背后的神经机制（AIM 1）。迄今为止，临床CI研究几乎完全采用了较低的空间频率轮廓元件（<7个周期/deg），但是收敛的证据表明，精神分裂症的特征是大细胞功能障碍，并且相应地处理了较低空间频率的受损处理（<8个周期摄氏度）。为了确定空间频率处理是否可以解释SZ中的CI缺陷，以后的情节患者组和匹配的健康对照组将执行4个不同的任务。每个任务的刺激的空间频率结构将变化为包括或不包括低空间频率。如果CI缺陷即使是由高空间频率定义的元素也会出现，那么早期视觉皮层中的横向相互作用受损将被证明是精神分裂症的核心特征。相比之下，如果仅在可用的空间频率可用时出现CI功能障碍，那么这将增加SZ中不断增长的大细胞功能障碍的证据，并将提供对CI任务的结果的新解释。在第二个数据收集阶段，我们将满足NIMH策略2.1并检查从第一集开始的CI缺陷的发展（AIM 2）。新招募的受试者将是健康对照，第一事件患者或晚期情节患者。第二阶段中的任务与在第一阶段揭示了组间差异（p <0.05）的任务相同。重要的是，此阶段将提供第一个数据，介绍了最近经历了第一个精神病性事件的精神分裂症患者中是否存在CI缺陷。在数据收集结束时，我们将在各个阶段组合数据以做出两个确定。首先，我们将评估高空间频率或较低空间频率的CI缺陷 - 与临床变量相关，例如：功能性结果，混乱的症状，正/阴性症状和病态的社会功能（AIM 3）。其次，我们将根据：组间效应大小，预测疾病特征的能力，总持续时间和辍学率（AIM 4）比较这四个任务（AIM 4）。以这种方式评估任务将指导未来的大规模研究，旨在进一步建立，解释或利用精神分裂症的轮廓缺陷。总而言之，在两个数据收集阶段实现的四个目标将阐明精神分裂症中轮廓整合功能障碍的神经机制，时间过程，临床相关性和最佳度量。 公共卫生相关性：符合NIMH策略1.1（“对基本的脑行为过程的综合理解……用于理解精神疾病”），拟议的研究将阐明大脑机制的基础，这些机制是降低空间分离轮廓能力的基础精神分裂症的元素。此外，与NIMH策略2.1一致（“定义精神障碍的发育轨迹”），拟议的研究将描述精神分裂症感知功能障碍的发育轨迹精神病的第一集。