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图（EEG）的神经同步性的措施，以检查精神分裂症的视觉感知神经回路的功能完整性。精神分裂症已被概念化为认知和神经过程整合的失败，并且神经回路（特别是抑制性中间神经元）的异常已被提出作为这种疾病的基础。越来越多的研究报告说，精神分裂症患者在脑电图的伽马（3）波段（30-100 Hz）表现出异常同步。这3种振荡被提出来通过将神经元动态地连接到功能组中来介导感知和认知过程，并且已知它们严重依赖于与精神分裂症中被干扰的抑制性中间神经元相同类型。因此，精神分裂症患者3个振荡的异常可能反映了这种疾病核心的神经回路异常。 在以前的工作中，我们已经发现，一个特殊的3振荡，响应锁定振荡（RLO），是敏感的核心症状的精神分裂症。在健康个体中，由真实的和虚幻的轮廓形成的物体引起视觉皮层不同区域上的3-波段RLO，而由两种类型的物体引起前额叶皮层上的RLO。在慢性精神分裂症患者中，由幻觉物体引起的枕叶RLO表现出2种异常：1）频率从3频带降低到β（2）频带（13-30 Hz）; 2）这种振荡的锁相程度与思维障碍和混乱症状测量以及幻视呈正相关。这些研究结果与完形知觉的心理物理学研究相吻合，后者发现精神分裂症谱系障碍中的知觉整合异常与混乱和思维障碍有关。此外，其他关于精神分裂症3振荡的研究也发现幻觉症状与3相位同步之间存在正相关。这些发现导致2个假设：1）枕RLO反映了一种基于同步的机制，该机制与感知特征绑定密切相关，并且对精神分裂症的主要神经回路异常和核心症状都很敏感; 2）RLO锁相和阳性症状之间的正相关反映了精神分裂症中神经回路不适当同步的倾向。 本研究将通过一系列的实验来检验这些假设，这些实验检测了慢性精神分裂症患者（SZ）和匹配的健康对照组（HC）。我们的具体目标是：1）将RLO异常的发现扩展到更广泛的完形过程; 2）调查导致SZ比HC发生RLO的频率更低的神经回路异常的基础; 3）将与组织解体学相关的完形知觉的行为异常与枕骨RLO联系起来，这表明与组织解体症状相关。 公共卫生相关性： 精神分裂症影响大约1%的普通人群，并对患者，他们的家庭和整个社会的个人，心理和财政健康产生深远的负面影响。这种疾病的特点是一个主要群体的患者在VHA，其中慢性精神病患者（主要是精神分裂症患者）占很大比例的VA精神卫生保健费用。为了治疗和最终预防精神分裂症，我们必须了解心灵和大脑是如何相互关联的。该项目旨在通过研究脑波同步如何与健康人和精神分裂症患者的感知和思维相关来进一步实现这一目标。

DESCRIPTION (provided by applicant): We propose to use measures of neural synchrony 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 circuitry (particularly inhibitory interneurons) have been proposed as a basis for this disorder. A growing number of studies have reported that individuals with schizophrenia demonstrate abnormal synchronization in the gamma (3) band of the EEG (30-100 Hz). These 3 oscillations have been proposed to mediate perceptual and cognitive processes by dynamically linking together neurons into functional groups, and are known to critically rely upon the same types of inhibitory interneurons as are disturbed in schizophrenia. Therefore, abnormalities in 3 oscillations in schizophrenia patients may reflect neural circuit abnormalities at the core of this disorder. In previous work we have found that a particular 3 oscillation, the response-locked oscillation (RLO), is sensitive to core symptoms of schizophrenia. In healthy individuals, 3-band RLOs over distinct areas of visual cortex are elicited by objects formed by both real and illusory contours, while an RLO over the prefrontal cortex is elicited by both types of objects. In chronic schizophrenia patients, the occipital RLO elicited by illusory objects exhibits 2 abnormalities: 1) the frequency is reduced from the 3 to the beta (2) band (13-30 Hz); and 2) the degree of phase-locking of this oscillation is positively correlated with thought disorder and disorganization symptom measures, as well as visual hallucinations. These findings converge with psychophysical studies of Gestalt perception, which have found that abnormalities of perceptual integration in schizophrenia-spectrum disorders are related to disorganization and thought disorder. Furthermore, other studies of 3 oscillations in schizophrenia have also found positive correlations between hallucination symptoms and 3 phase synchrony. These findings lead to 2 hypotheses: 1) the occipital RLO reflects a synchrony-based mechanism that is closely involved in perceptual feature-binding, and is sensitive to both primary neural circuitry abnormalities and core symptoms in schizophrenia; and 2) the positive correlations between RLO phase locking and positive symptoms reflect a propensity for neural circuits to synchronize inappropriately in schizophrenia. This project will test these hypotheses in a series of experiments examining chronic schizophrenia patients (SZ) and matched healthy control subjects (HC). Our specific aims are to: 1) extend the findings of RLO abnormalities to a broader range of Gestalt processes; 2) investigate the basis of the neural circuit abnormality that causes the RLO to occur at a lower frequency in SZ than HC; 3) connect the behavioral abnormalities of Gestalt perception that are associated with disorganization symptomatology and the occipital RLO, which shows correlations with disorganization symptoms. PUBLIC HEALTH RELEVANCE: Schizophrenia affects approximately 1% of the general population and has profound negative consequences for the personal, psychological, and fiscal well being of patients, their families, and society as a whole. This disorder characterizes a major group of patients in the VHA, where the chronically mentally ill (primarily patients with schizophrenia) account for a large proportion of VA mental healthcare costs. To treat and ultimately prevent schizophrenia, we must understand how the mind and brain are interrelated. This project seeks to further this goal by studying how brainwave synchronization is related to perception and thinking in people who are healthy, and in people who have schizophrenia.