Spatial frequency contributions to contour integration deficits in schizophrenia

描述（由申请人提供）：轮廓整合(CI)-就本申请而言-是指将空间隔离的边缘表示为单个连续轮廓的能力。大量研究表明，精神分裂症患者（SZ）的轮廓整合功能受损，但其机制、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）。迄今为止，临床CI研究几乎完全采用了较低空间频率的轮廓元素（<7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（<8周期度）的处理受损。为了确定空间频率处理是否可以解释SZ的CI缺陷，一个发作后的患者组和一个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会发生变化，包括或不包括低空间频率。如果CI缺陷出现在由高空间频率定义的元素上，那么早期视觉皮层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CI功能障碍只在较低的空间频率出现时才会出现，那么这将增加SZ中大细胞功能障碍的证据，并将为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策略2.1，并检查从首发开始CI缺陷的发展（目标2）。新招募的受试者要么是健康对照，要么是首发患者，要么是后发患者。第二阶段的任务与第一阶段的组间差异（p<0.05）相同。重要的是，这一阶段将提供关于最近经历第一次精神病发作的精神分裂症患者中是否存在CI缺陷的第一批数据。在数据收集结束时，我们将合并各个阶段的数据以做出两个决定。首先，我们将评估CI缺陷（高或低空间频率）是否与临床变量相关，如：功能结果、紊乱症状、阳性/阴性症状和病前社会功能（目标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（目标4）来比较这四个任务。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，通过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、时间过程、临床相关性和最佳测量方法。

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.