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）中的神经同步测量来检查精神分裂症神经回路的功能完整性。精神分裂症被定义为认知整合的失败，神经回路异常（特别是抑制性中间神经元）被认为是这种疾病的基础。越来越多的研究报道，精神分裂症患者在脑电图的“伽马”波段（30-100赫兹）表现出异常的同步。伽马振荡可能介导知觉和认知过程，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伽马波段脑电图振荡异常反映了神经回路同步功能障碍。在我们对慢性精神分裂症患者（SZ）和健康对照（HC）的研究中，我们发现了一些与感觉和知觉加工相关的伽马振荡异常。1)利用听觉稳态反应（ASSRs）探测听觉皮层神经回路完整性的研究中，SZ表现出伽马频率刺激引起的ASSRs减少，而低频刺激则没有。2) SZ的早期视觉刺激诱发振荡（SEO）与刺激或任务要求无关。相比之下，复杂声音而非简单音调所诱发的听觉SEO在SZ中减少，因此这种缺陷可能与刺激特征有关。3)在利用格式塔刺激检验视觉特征绑定机制的研究中，SZ区的响应锁定振荡（RLO）在gamma到beta频率范围内频率降低。RLO相锁与SZ患者的思维障碍、概念障碍和视幻觉症状呈正相关。这些数据和其他数据表明，精神分裂症与各种感觉和感知相关的伽马振荡异常有关。为了阐明精神分裂症中伽马振荡所表现的功能失调的神经动力学，我们建议在慢性SZ和匹配的HC中进行以下研究。振荡的大脑活动将使用基于小波的时频方法进行测量。我们的具体目标是：1)确定ASSR γ驱动缺陷的潜在因素；2)确定刺激特征和注意需求对听觉和视觉搜索引擎优化缺陷的影响；3)揭示SZ ASSR和SEO缺陷背后的振荡动力学。为了治疗并最终预防神经精神疾病，我们必须了解精神和大脑是如何相互关联的。该项目旨在通过研究健康人以及精神分裂症患者的脑波同步如何与感知和思考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.