Spatial frequency contributions to contour integration deficits in schizophrenia

描述(由申请人提供)：为了本申请的目的，轮廓集成(CI)指的是将空间分离的边表示为单个连续轮廓的能力。大量研究表明，精神分裂症(SZ)患者在轮廓整合方面受到损害，但这种损害的机制、时间进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战略1.1，并阐明赤字背后的神经机制(目标1)。到目前为止，临床CI研究几乎完全采用了较低的空间频率轮廓元素(&lt；7个周期/度)，但越来越多的证据表明，精神分裂症的特征是大细胞功能障碍，相应地，对较低空间频率的处理也受到损害(&lt；8个周期/度)。为了确定空间频率处理是否可以解释SZ的CI缺陷，一个晚期患者组和一个匹配的健康对照组将执行四个不同的任务。每个任务的刺激的空间频率结构将改变，以包括或不包括低空间频率。如果CI缺陷甚至出现在由高空间频率定义的元素上，那么早期视觉皮质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，如果只有当空间频率较低时才会出现CI功能障碍，那么这将增加SZ大细胞功能障碍的越来越多的证据，并将对CI任务产生的结果提供新的解释。在第二个数据收集阶段，我们将满足NIMH战略2.1，并检查从第一集开始的CI赤字的发展(目标2)。新招募的受试者将是健康对照组、首发患者或晚发患者。第二阶段的任务将与第一阶段显示的组间差异(p&lt；0.05)相同。重要的是，这一阶段将提供关于最近经历了第一次精神病发作的精神分裂症患者中是否存在CI缺陷的第一个数据。在数据收集结束时，我们将跨阶段合并数据以做出两个确定。首先，我们将评估CI缺陷--空间频率高或低--是否与临床变量相关，如：功能结果、紊乱症状、阳性/阴性症状和发病前社会功能(目标3)。其次，我们将从以下几个方面对这四项任务进行比较：组间效应大小、预测疾病特征的能力、总病程和辍学率(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患者轮廓整合功能障碍的神经机制、时间进程、临床相关性和最佳措施。 与公共卫生相关：根据NIMH战略1.1(“建立对基本大脑行为过程的综合理解……以了解精神疾病”)，拟议的研究将阐明精神分裂症患者连接空间分离轮廓元素的能力降低的大脑机制。此外，根据NIMH战略2.1(“定义精神障碍的发展轨迹”)，拟议的研究将描述精神分裂症知觉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第一次发作时就存在的第一批实质性数据。

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.