Neurophysiological Studies of Visual Perception in Schizophrenia

描述(由申请人提供)： 我们建议使用头皮记录脑电(EEG)中振荡活动的测量来检查精神分裂症患者视觉感知基础神经回路的功能完整性。精神分裂症被认为是一种认知和神经过程整合的失败，神经微电路的异常被认为是这种疾病的基础。越来越多的证据表明，脑电上频段的振荡，即贝塔(：13-30赫兹)和伽马(：30-100赫兹)频段，调节着涉及视觉感知的特定功能。我们假设精神分裂症的异常和振荡可能反映了与精神分裂症有关的特定神经微电路异常。拟议的研究将建立在前一个项目阶段的基础上，在该项目期间，我们检查了反应锁定振荡(RLO)、知觉特征绑定和精神分裂症症状之间的关系。在下一个项目阶段，我们建议使用一种统一的方法来研究精神分裂症的振荡异常：知觉决策。这种方法包括跟踪一个简单的知觉决定从刺激到反应处理阶段的演变。对动物和人类的研究支持一个基本模型，在这个模型中，感觉区域的刺激编码由多模式关联区域读出，在这些区域中，感知证据积累并形成决策。然后，决策信息被传输到运动皮质，并做出反应。振荡研究表明，和振荡可能起着不同的作用，其中振荡反映了感觉和反应过程的局部计算，振荡涉及到注意控制和维持知觉决定背后的刺激-反应映射。因此，知觉决策方法将使我们能够识别深圳信息处理的特定方面的异常，并与 这些异常表现在患者的症状上。我们假设：1)SZ在感觉编码、证据积累和反应选择过程中存在独立的缺陷；2)精神症状，如组织混乱和思维障碍，与证据积累过程障碍密切相关；3)自上而下的控制缺陷导致证据积累障碍和精神症状关系。我们的具体目标是：1)将特征绑定从感知决策过程中分离出来。我们的标准Kanisza形状感知任务将被修改为支持两种不同的判断：形状存在/不存在，以及区分诱导者属性。我们预测，在深圳，知觉非依赖性决策过程将是异常的，并与阳性症状相关。2)使用连贯的运动检测任务，检查SZ中知觉决策的哪些阶段(感觉编码、证据积累和反应选择)异常。我们预测，虽然深圳的所有三个阶段都将受到损害，但这些损害将相互独立。证据积累的一种衡量标准将与精神病症状呈正相关。3)通过使用线索操纵被试在连贯运动检测任务中对刺激的期望，考察了自上而下加工在SZ异常中的作用。我们预测，自上而下的过程将与感觉和决策过程相互作用，并将影响深圳决策过程与精神症状之间的关系。我们希望这些研究的结果将导致对精神分裂症潜在的认知和神经机制的更深入的理解，从而能够识别用于治疗开发的生物标记物。

DESCRIPTION (provided by applicant): We propose to use measures of oscillatory activity in the scalp-recorded electroencephalogram (EEG) to examine the functional integrity of the neural circuitry underlying visual perception in schizophrenia. Schizophrenia has been conceptualized as a failure of the integration of cognitive and neural processes, and abnormalities in neural microcircuitry have been proposed as a basis for this disorder. There is growing evidence that oscillations in the upper frequency bands of the EEG, the beta ( : 13-30 Hz) and gamma ( : 30- 100 Hz) bands, mediate particular functions involved in visual perception. We hypothesize that abnormalities of and oscillations may reflect particular neural microcircuit abnormalities involved in schizophrenia. The proposed studies will build upon the previous project period in which we examined the relationships between response-locked oscillations (RLOs), perceptual feature-binding, and schizophrenia symptomatology. In the next project period we propose to use a unified approach to study oscillation abnormalities in schizophrenia: perceptual decision making. This approach involves tracking the evolution of a simple perceptual decision from stimulus to response stages of processing. Studies in animals and humans support a basic model in which stimulus encoding in sensory areas is read-out by multimodal association areas in which perceptual evidence accumulates and decisions are formed. Decision information is then transmitted to motor cortex and a response is made. Oscillation studies suggest that and oscillations may play distinct roles, with oscillations reflecting local computations of sensory and response processes, and oscillations involved in attentional control and maintaining stimulus-response mappings underlying the perceptual decision. Therefore, the perceptual decision making approach will allow us to identify abnormalities in particular aspects of information processing in SZ and relate these abnormalities to the patients' symptomatology. We hypothesize that: 1) SZ have independent deficits in sensory encoding, evidence accumulation, and response selection processes; 2) psychotic symptoms, such as disorganization and thought disorder, are closely related to dysfunctional evidence accumulation processes; and 3) top-down control deficits contribute to evidence accumulation impairments and psychotic symptom relationships. Our specific aims are to: 1) Dissociate feature binding from perceptual decision processes. Our standard Kanisza shape perception task will be modified to support 2 different judgments: shape presence/absence, and distinguishing between inducer attributes. We predict that perception-independent decisional processes will be abnormal and correlated with positive symptoms in SZ. 2) Examine which phases of perceptual decision making (sensory encoding, evidence accumulation, and response selection) are abnormal in SZ, using a coherent motion detection task. We predict that while all three phases will be impaired in SZ, these impairments will be independent of each other. A measure of evidence accumulation will be positively correlated with psychotic symptoms. 3) Examine the role of top-down processes in SZ abnormalities in perceptual decision making by manipulating subjects' expectancies about the stimuli in the coherent motion detection task using cues. We predict that top-down processes will interact with both sensory and decisional processes, and will influence the relationships between decisional processes and psychotic symptoms in SZ. We hope that the results of these studies will lead to a deeper understanding of the cognitive and neural mechanisms underlying schizophrenia, enabling the identification of biomarkers for treatment development.