Neural Dynamics in Schizophrenia

描述（由申请人提供）：本项目将使用头皮记录脑电图（EEG）中的神经同步措施来检查精神分裂症神经回路的功能完整性。精神分裂症已被概念化为认知整合的失败，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”波段（30-100 Hz）表现出异常同步。伽马振荡可以介导感知和认知过程，并且已知依赖于抑制性中间神经元。因此，我们认为精神分裂症患者的γ-波段脑电振荡异常反映了神经回路的同步功能障碍。在我们对慢性精神分裂症患者（SZ）和健康对照组（HC）的研究中，我们发现了几种与感觉和知觉处理相关的伽马振荡异常。1)在使用听觉稳态反应（ASSRs）来探测听觉皮层神经回路完整性的研究中，SZ显示由伽马频率刺激引起的ASSRs减少，但在较低频率下的刺激不减少。2)早期视觉刺激诱发的振荡（SEO）似乎减少SZ无论刺激或任务的要求。与此相反，听觉SEO引起的复杂的声音，但不是简单的音调是减少在SZ，因此，这种赤字可能与刺激功能。3)在研究中，利用完形刺激检查视觉功能结合机制，响应锁定振荡（RLO）可能与功能结合的频率降低，从伽玛到β频率范围在SZ。SZ患者的RLO相位锁定与思维障碍、概念紊乱和幻视症状呈正相关。这些数据和其他数据表明，精神分裂症与各种感觉和知觉相关的伽马振荡异常有关。为了阐明精神分裂症中γ振荡所表现的功能失调的神经动力学，我们提出了以下研究慢性SZ和匹配的HC。振荡脑活动将使用基于小波的时间-频率方法测量。我们的具体目标是：1）确定ASSR伽马驱动缺陷的潜在因素; 2）确定刺激特征和注意力需求对听觉和视觉SEO缺陷的影响; 3）揭示SZ ASSR和SEO缺陷的振荡动力学。为了治疗并最终预防神经精神疾病，我们必须了解大脑和心灵是如何相互关联的。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): This project will use measures of neural synchrony in the scalp-recorded electroencephalogram (EEG) to examine the functional integrity of neural circuitry in schizophrenia. Schizophrenia has been conceptualized as a failure of cognitive integration, 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" band of the EEG (30-100 Hz). Gamma oscillations may mediate perceptual and cognitive processes, and are known to rely upon inhibitory interneurons. Therefore, we propose that abnormalities in gamma-band EEG oscillations in schizophrenia patients reflect dysfunctional synchronization of neural circuitry. In our studies of chronic schizophrenia patients (SZ) and healthy control subjects (HC) we have identified several abnormalities in gamma oscillations related to sensory and perceptual processing. 1) In studies using auditory steady-state responses (ASSRs) to probe the integrity of neural circuitry in auditory cortex, SZ show reductions in the ASSRs evoked by gamma frequency stimulation, but not by stimulation at lower frequencies. 2) The early visual stimulus-evoked oscillation (SEO) appears to be reduced in SZ irrespective of stimuli or task demands. In contrast, the auditory SEO evoked by complex sounds but not simple tones is reduced in SZ, and thus this deficit may be related to stimulus features. 3) In studies utilizing Gestalt stimuli to examine visual feature-binding mechanisms, a response-locked oscillation (RLO) potentially related to feature-binding was reduced in frequency from the gamma to the beta frequency range in SZ. RLO phase locking was positively correlated with thought disorder, conceptual disorganization, and visual hallucination symptoms in SZ. These data and others demonstrate that schizophrenia is associated with abnormalities in a variety of sensory- and perception-related gamma oscillations. To elucidate the dysfunctional neural dynamics that are manifested by gamma oscillations in schizophrenia, we propose the following studies in chronic SZ and matched HC. Oscillatory brain activity will be measured using wavelet-based time-frequency methods. Our specific aims are to: 1) determine the factors underlying the ASSR gamma driving deficit; 2) determine the effects of stimulus features and attentional demands on the deficits of the auditory and visual SEOs; 3) reveal the oscillatory dynamics underlying the ASSR and SEO deficits in SZ. PUBLIC HEALTH RELEVANCE To treat and ultimately prevent neuropsychiatric disorders, 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.