Functional Imaging /Stimulus Processing /Encoding /Schiz

功能成像/刺激处理/编码/Schiz

• 批准号: 7161999
• 负责人: Raquel E Gur
• 金额: $ 27.43万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7161999
• 关键词: auditory stimulus; behavioral /social science research tag; bioimaging /biomedical imaging; blood oxygenator; cognition; computer data analysis; data management; electrophysiology; evoked potentials; functional magnetic resonance imaging; hemodynamics; human subject; neural information processing; neuroanatomy; neuroimaging; neuropsychological tests; neuropsychology; patient oriented research; performance; schizophrenia; sensory cortex; short term memory; stimulus interval; thalamocortical tract; visual stimulus

Functional MRI (fMRI) permits evaluation of distributed brain systems that encode incoming stimuli. It offers anatomic localization of neural activation, complementing the temporal resolution of electrophysiology. Most fMRI studies in schizophrenia have focused on fronto-temporal "executive" systems. However, evidence from the current CCNMD studies, consistent with an extensive ERP and a growing fMRI literature, indicate impaired activation and deficits in early stages of stimulus encoding. Current studies, and data from Project I, suggest abnormal alterations in gamma oscillations in schizophrenia, most consistently for induced gamma. Such abnormalities implicate deficits in coordinating activity in multiple regions that use phase locked gamma frequency oscillations. Gamma oscillations have lately been linked to hemodynamic signal changes in both the visual and the auditory modalities. The proposed project will combine homologous visual and auditory paradigms, in parallel with electrophysiology (Project I), to investigate early stages of stimulus encoding, focusing on integration. The dimensions of stimulus modality, the required integration (spatial, temporal or both), and the nature of controlled-processing demands (top-down vs. bottom-up), will be systematically manipulated. We will use event-related designs, in a high-field scanner (3 Tesla), to model the hemodynamic response for each stimulus class. Another new direction in the project will build on our genetic studies in schizophrenia. We have established that neurocognitive measures are potential endophenotypic markers of vulnerability present in unaffected family members. The sample will include 80 patients with schizophrenia, 80 first-degree unaffected family members and 80 unrelated healthy people. The CCNMD hypothesis will be tested by implementing a cascade of fMRI studies that capitalize on the complementarity between electrophysiology and fMRI. Parallel studies will be performed within the auditory and visual modalities and each participant will undergo both sensory conditions as well as the electrophysiologic studies described in subproject 0001. The cascade will trace the stages of information processing from stimulus deviance and novelty detection through encoding using adaptation to fMRI of standard electrophysiologic tasks that have been associated with specific components of the ERP. The neurobehavioral probes will examine regional activation induced by target detection, response to novelty and recognition memory. Physiological activity will be measured with the BOLD paradigm using event-related contrasts to help establish the stage of information processing in the cortico-thalamic network where patients show abnormal activation. Magnitude and spatial extent of activation will be related to: a. on-line performance for tasks requiring response, with both accuracy and reaction time available, b. Basal neurocognitive computerized measures obtained by Core A, which yield estimates of accuracy and speed for eight neurocognitive domains; c. clinical parameters assessed by Core A, which provide measures of symptoms, functioning and course. The targeted sampling by DTNBP1, NRG1 and RGS4 will permit linking activation abnormalities to vulnerability haplotype.

功能性MRI（fMRI）允许评估编码传入刺激的分布式大脑系统。它提供 神经激活的解剖学定位，补充电生理学的时间分辨率。最多 精神分裂症的功能磁共振成像研究集中在额叶“执行”系统上。但是，来自 当前的CCNMD研究与广泛的ERP和不断增长的fMRI文献一致，表明 在刺激编码的早期阶段，激活和缺陷受损。当前的研究以及项目I的数据， 表明精神分裂症中γ振荡的异常改变，对于诱导的伽马，最持续的变化。 这种异常暗示在使用相位锁定相的多个区域进行协调活动中的缺陷 伽马频率振荡。 γ振荡最近与血液动力学信号变化有关 在视觉和听觉方式中。 拟议的项目将与同源的视觉和听觉范式结合在一起 电生理学（项目I），研究刺激编码的早期阶段，专注于整合。这 刺激方式，所需集成（空间，时间或两者）的维度以及 受控处理的需求（自上而下与自下而上）将被系统地操纵。我们将使用 在高场扫描仪中与事件相关的设计（3特斯拉），以建模每个 刺激课。该项目的另一个新方向将基于我们在精神分裂症中的遗传研究。我们 已经确定神经认知措施是脆弱性的潜在内表型标记 在未受影响的家庭成员中。样本将包括80例精神分裂症患者，80个一级 未受影响的家庭成员和80个无关的健康人。 CCNMD假设将通过 实施一系列fMRI研究，以利用电生理学之间的互补性 和fMRI。并行研究将在听觉和视觉方式中进行，每个参与者将 接受了0001 0001中描述的感官条件以及电生理研究。 级联将从刺激偏差和新颖性检测中追踪信息处理的阶段 使用适应与已经相关的标准电生理任务的fMRI进行编码 ERP的特定组成部分。神经行为探针将检查由 目标检测，对新颖性和识别记忆的反应。生理活动将通过 使用与事件相关的对比的大胆范式来帮助建立信息处理的阶段 患者表现出异常激活的皮质 - 丘脑网络。激活的大小和空间范围 将与：需要响应的任务的在线性能，同时具有准确性和反应时间 可用，b。通过核心A获得的基础神经认知计算机测量，该测量的产量估计值 八个神经认知领域的准确性和速度； c。由核心A评估的临床参数，该参数 提供症状，功能和病程的度量。 DTNBP1，NRG1和 RGS4将允许将激活异常与脆弱性单倍型联系起来。