Early Cortical Processing in Schizophrenia

精神分裂症的早期皮质处理

基本信息

项目摘要

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)与代表该疾病核心特征的认知功能缺陷相关。传统的多巴胺能模型在高阶关联大脑区域内产生应激功能障碍。相比之下,最近的谷氨酸能模型预测整个皮质区域(包括初级和次级感觉皮质)存在广泛的功能障碍。在过去的项目期间,我们使用基于行为、事件相关电位 (ERP) 和 MRI 的方法记录了 Sz 早期听觉和视觉处理的缺陷,支持 Sz 皮质功能障碍的分布式模型。此外,我们还证明了早期感觉处理缺陷对高阶皮质损伤的重要贡献。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具体假设,以及开发潜在治疗方法的新方法。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,以及失配负性 (MMN)、听觉 N1 和听觉稳态 (ASSR) 反应的生成受损。此外,低水平听觉处理的缺陷会导致高级功能障碍,例如解释韵律的能力受损,导致听觉情绪识别(AER)缺陷,进而导致社会功能受损。在视觉系统中,缺陷包括对比敏感度降低,特别是对优先参与大细胞视觉系统的低对比度、低空间频率 (LSF) 刺激,以及稳态视觉诱发电位 (ssVEP)、视觉 P1 和受损的生成初级视觉皮层大细胞受体区域的功能磁共振成像激活。低水平的缺陷会导致更高阶的损伤,包括知觉闭合和面部情绪识别(FER)。听觉和视觉缺陷都会导致阅读能力逐渐受损,这可能是 Sz 的早期标志。最后,根据弥散张量 (DTI) 和静息态 (rsfMRI) 成像的评估,听觉和视觉缺陷都与低水平感觉区域内的结构和功能连接受损相关。迄今为止,神经生理学异常主要使用时域方法进行评估。在接下来的一段时间内,我们还将结合先进的频域和振荡分层方法,这些方法提供神经元振荡的自发和事件相关动力学的单独指数。视觉 ERP 将与眼动追踪相结合,以评估自然场景处理。我们还将使用我们之前资助周期中验证的范例来探索前驱期和首发 (FE) 队列中的功能障碍模式。最后,我们将采用新颖的大脑刺激方法,包括应用于感觉与额叶皮层区域的经颅磁刺激(rTMS),以破坏健康对照中的局部处理,作为模型 尺寸;以及应用于感觉或额叶脑区域的经颅直流电刺激 (tDCS),作为 Sz 中基于可塑性的刺激干预的前奏。

项目成果

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DANIEL C. JAVITT其他文献

DANIEL C. JAVITT的其他文献

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{{ truncateString('DANIEL C. JAVITT', 18)}}的其他基金

Auditory event-related potentials as in vivo preclinical assays of circuit engagement for E/I-based therapeutic development
听觉事件相关电位作为基于 E/I 的治疗开发的电路参与的体内临床前测定
  • 批准号:
    10717704
  • 财政年份:
    2023
  • 资助金额:
    $ 10.87万
  • 项目类别:
Neural Mechanisms of Reading Dysfunction in Schizophrenia
精神分裂症阅读障碍的神经机制
  • 批准号:
    10399585
  • 财政年份:
    2020
  • 资助金额:
    $ 10.87万
  • 项目类别:
Neural Mechanisms of Reading Dysfunction in Schizophrenia
精神分裂症阅读障碍的神经机制
  • 批准号:
    10640071
  • 财政年份:
    2020
  • 资助金额:
    $ 10.87万
  • 项目类别:
Neural Mechanisms of Reading Dysfunction in Schizophrenia
精神分裂症阅读障碍的神经机制
  • 批准号:
    10200005
  • 财政年份:
    2020
  • 资助金额:
    $ 10.87万
  • 项目类别:
Temporal dynamics of neurophysiological patterns as treatment targets in Sz
作为 Sz 治疗目标的神经生理模式的时间动态
  • 批准号:
    9055968
  • 财政年份:
    2016
  • 资助金额:
    $ 10.87万
  • 项目类别:
tDCS Augmentation of Cognitive Remediation in Schizophrenia
tDCS 增强精神分裂症认知修复
  • 批准号:
    8584098
  • 财政年份:
    2013
  • 资助金额:
    $ 10.87万
  • 项目类别:
tDCS Augmentation of Cognitive Remediation in Schizophrenia
tDCS 增强精神分裂症认知修复
  • 批准号:
    8717732
  • 财政年份:
    2013
  • 资助金额:
    $ 10.87万
  • 项目类别:
Administrative
行政的
  • 批准号:
    8105225
  • 财政年份:
    2010
  • 资助金额:
    $ 10.87万
  • 项目类别:
The Conte Center for Schizophrenia Research
康特精神分裂症研究中心
  • 批准号:
    8337017
  • 财政年份:
    2010
  • 资助金额:
    $ 10.87万
  • 项目类别:
The Conte Center for Schizophrenia Research
康特精神分裂症研究中心
  • 批准号:
    8061041
  • 财政年份:
    2010
  • 资助金额:
    $ 10.87万
  • 项目类别:

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在小鼠主动声音定位过程中将听觉输入与头部位置整合的中枢听觉通路
  • 批准号:
    10652787
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用于神经记录和刺激的自主快速自适应多光子显微镜
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    10739050
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Neural and Behavioral Indices of Balance Performance in Individuals with sensory loss
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    10751174
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