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）：轮廓整合（CI）-对于本申请的目的-是指将空间分离的边缘表示为单个连续轮廓的能力。许多研究表明，精神分裂症（SZ）患者的轮廓整合受损，但损伤的机制，时间过程和临床意义才刚刚开始探索。为了阐明这个问题，我们进行了两个阶段的心理物理调查。在第一阶段，我们将满足NIMH策略1.1，并阐明缺陷背后的神经机制（目标1）。迄今为止，临床CI研究几乎完全采用较低空间频率轮廓元素（<7周期/度），但汇聚的证据表明，精神分裂症的特征是大细胞功能障碍，相应地，较低空间频率（<8周期/度）的加工受损。为了确定空间频率处理是否可以解释SZ中的CI缺陷，晚发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被改变以包括或不包括低空间频率。如果出现CI赤字，甚至与高空间频率定义的元素，然后受损的横向相互作用在早期视觉皮层将被证明是精神分裂症的核心特征。相比之下，如果CI功能障碍只出现在较低的空间频率时，那么这将增加越来越多的证据，大细胞功能障碍在SZ，并将提供一个新的解释的结果来自CI任务。在第二个数据收集阶段，我们将满足NIMH策略2.1，并检查从第一次发病开始CI缺陷的发展（目标2）。新招募的受试者将是健康对照、首次发作患者或晚期发作患者。第二阶段的任务将与第一阶段中显示组间差异（p<0.05）的任务相同。重要的是，这一阶段将提供关于最近经历过第一次精神病发作的精神分裂症患者是否存在CI缺陷的第一批数据。在数据收集结束时，我们将联合收割机跨阶段的数据进行组合，以做出两个决定。首先，我们将评估CI缺陷-在高或低空间频率-与临床变量，如：功能结果，紊乱的症状，阳性/阴性症状，和病前社会功能（目标3）。其次，我们将比较四个任务的基础上：组间效应大小，预测疾病特征的能力，总持续时间和辍学率（目标4）。以这种方式评估任务将指导未来更大规模的研究，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轮廓整合功能障碍的神经机制，时间过程，临床相关因素和最佳措施。 公共卫生相关性：雅阁NIMH战略1.1（“发展对基本大脑行为过程的综合理解......为了理解精神疾病”），拟议的研究将阐明精神分裂症患者连接空间分离的轮廓元素的能力降低的大脑机制。此外，与NIMH策略2.1（“定义精神障碍的发展轨迹”）一致，拟议的研究将描述精神分裂症感知功能障碍的发展轨迹，并提供关于轮廓整合障碍是否早在精神病首次发作时就存在的第一个实质性数据。