Early Cortical Processing in Schizophrenia

精神分裂症的早期皮质处理

• 批准号: 8908263
• 负责人: DANIEL C. JAVITT
• 金额: $ 10.87万
• 依托单位: NATHAN S. KLINE INSTITUTE FOR PSYCH RES
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-03 至 2018-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8908263
• 关键词: Auditory; Auditory system; Behavioral; Brain; Brain region; Cognitive; Cognitive deficits; Cognitive remediation; Complex; Contrast Sensitivity; Coupling; Detection; Diffusion; Disease; Electroencephalography; Emotions; Evaluation; Event; Event-Related Potentials; Eye; Face; Facial Expression; Frequencies; Functional Magnetic Resonance Imaging; Functional disorder; Future; Generations; Glutamates; Grant; Health; Image; Impaired cognition; Impairment; Individual; Intervention; Lead; Magnetic Resonance Imaging; Measures; Modeling; Neurons; Patients; Pattern; Perceptual Closure; Phase; Population; Process; Reading; Rest; Schizophrenia; Sensory; Sensory Process; Social Functioning; Speech; Stimulus; Stress; Therapeutic; Transcranial magnetic stimulation; Visual; Visual Motion; Visual evoked cortical potential; Visual system structure; Voice; area striata; base; cognitive function; cohort; disability; functional outcomes; improved; indexing; insight; magnocellular; neuromechanism; neurophysiology; neuropsychiatry; novel; novel strategies; reading ability; response; sensory cortex; social cognition; therapy development; time use; tool; visual process; visual processing

DESCRIPTION (provided by applicant): Schizophrenia (Sz) is associated with deficits in cognitive function that represent a core feature of the disorder. Traditional dopaminergic models stress dysfunction within higher order associational brain regions. In contrast, more recent glutamatergic models predict widespread dysfunction across cortical regions, including primary and secondary sensory cortices. Over the past project period, we have documented deficits in early auditory and visual processing in Sz using behavioral-, event-related potential (ERP) and MRI-based approaches, supporting distributed models of cortical dysfunction in Sz. In addition, we have demonstrated significant contributions of early sensory processing deficits to higher order cortical impairments. These studies have permitted us to formulate specific hypotheses concerning neural mechanisms underlying sensory/cognitive dysfunction in Sz, as well as novel approaches to potential treatment development. In the auditory system, early deficits include impaired ability to match tones following brief delay, as well as impaired generation of mismatch negativity (MMN), auditory N1 and auditory steady-state (ASSR) responses. Furthermore, deficits in low level auditory processing contribute to higher order dysfunction, such as impaired ability to interpret prosody, leading to deficits in auditory emotion recognition (AER), which, in turn, contributes to impaired social function. In the visual system, deficits include reduced contrast sensitivity particularly to low contrast, low spatial frequency (LSF) stimuli that preferentially engage the magnocellular visual system, as well as impaired generation of steady state visual evoked potentials (ssVEP), visual P1, and impaired fMRI activation of magnocellular-recipient regions of primary visual cortex. Low level deficits contribute to higher order impairments including in perceptual closure and face emotion recognition (FER). Both auditory and visual deficits contribute to progressive impairment in reading ability, which may be an early marker of Sz. Finally, both auditory and visual deficits correlate with impaired structura and functional connectivity within low level sensory regions, as assessed using diffusion tensor (DTI) and resting state (rsfMRI) imaging. To date, neurophysiological abnormalities have been assessed mainly using time-domain approaches. Over the upcoming period, we will incorporate advanced frequency-domain and oscillatory hierarchical approaches as well, which provide separate indices of spontaneous and event-related dynamics of neuronal oscillations. Visual ERP will be combined with eye tracking to permit evaluation of naturalistic scene processing. We will also explore patterns of dysfunction within both prodromal and first episode (FE) cohorts using paradigms validated during our prior grant cycle. Finally, we will incorporate novel brain stimulation approaches including Transcranial Magnetic Stimulation (rTMS) applied over sensory vs. frontal cortical regions to disrupt local processing in healthy controls as a model for Sz; and transcranial Direct Current Stimulation (tDCS) applied over sensory or frontal brain regions as a prelude to plasticity-based stimulatory intervention in Sz.

描述（由申请人提供）：精神分裂症（SZ）与代表该疾病的核心特征的认知功能缺陷有关。传统的多巴胺能模型在高阶关联大脑区域内强调功能障碍。相反，最近的谷氨酸能模型可以预测皮质区域（包括原发性和次级感觉皮质）之间的广泛功能障碍。在过去的项目期间，我们使用行为 - 事件相关电位（ERP）和基于MRI的方法记录了SZ早期听觉和视觉处理的缺陷，支持SZ中皮质功能障碍的分布式模型。此外，我们已经证明了早期感觉处理缺陷对高阶皮质障碍的重要贡献。这些研究使我们能够提出有关SZ感觉/认知功能障碍的神经机制的特定假设，以及潜在治疗发展的新方法。在听觉系统中，早期缺陷包括短暂延迟后匹配音调的能力受损，以及不匹配负效率（MMN），听觉N1和听觉稳态（ASSR）响应受损的能力。此外，低水平的听觉处理缺陷会导致高阶功能障碍，例如解释韵律的能力受损，导致听觉情绪识别（AER）的缺陷，这反过来又导致社会功能受损。 In the visual system, deficits include reduced contrast sensitivity particularly to low contrast, low spatial frequency (LSF) stimuli that preferentially engage the magnocellular visual system, as well as impaired generation of steady state visual evoked potentials (ssVEP), visual P1, and impaired fMRI activation of magnocellular-recipient regions of primary visual cortex.低水平的赤字有助于高阶障碍，包括感知闭合和面对情绪识别（FER）。听觉和视觉缺陷都导致阅读能力的逐步损害，这可能是SZ的早期标志。最后，听觉和视觉缺陷都与低级感觉区域内的结构和功能连接性受损相关，如使用扩散张量（DTI）和静止状态（RSFMRI）成像评估。迄今为止，主要使用时间域方法评估了神经生理异常。在接下来的时期，我们还将结合先进的频域和振荡性层次方法，这些方法提供了神经元振荡的自发和事件相关动力学的单独索引。 Visual ERP将与眼睛跟踪相结合，以允许评估自然主义场景处理。我们还将使用在我们先前的授予周期中验证的范式探索前驱动物和第一集（Fe）同类群体中功能​​障碍的模式。最后，我们将结合新型的大脑刺激方法，包括在感觉与额叶皮质区域应用于颅骨磁刺激（RTM），以破坏健康对照中的局部加工作为模型 SZ;在感觉或额叶大脑区域应用于SZ中基于可塑性的刺激干预的前奏，应用于感觉或额叶大脑区域的经颅直流刺激（TDC）。