Auditory Cortex Structure and Function in Schizophrenia

描述（由申请人提供）：听觉信息处理能力的缺陷被认为是精神分裂症（Sz）的核心异常之一。尽管这门学科很重要，但我们对正常或异常听觉加工的机制知之甚少，也不清楚听觉缺陷的临床意义。研究越来越多地关注与听觉过程相关的大脑时间频率活动，因为假设单次试验的振幅和相位测量更能反映神经过程。正如在K08提案中详述的那样，我最近的颞上回（STG）时频发现建立在并极大地扩展了这一研究领域的发现，目前的结果表明，在理解和治疗Sz方面有可能取得进展的几个明确的研究方向。在K08研究中，使用为K08项目开发的新任务，将对50名对照者和50名患者进行全脑听觉活动的功能测量（脑电图和脑磁图）。有3个实质性的研究目标：(1)通过检查听觉网络中的多个节点，并通过对每个过程（编码vs门控，振幅vs锁相）的多重评估来确定Sz听觉异常的性质；(2)通过改变注意力aI/任务集要求来确定异常听觉过程是否可以在Sz患者中正常化；(3)确定观察到的异常的临床意义。假设存在编码锁相缺陷，并且假设这种异常与认知问题和阴性症状增加有关。K08培训是对K08研究的补充。K08的主要训练目标包括：(1)研究几种新的分布式源定位方法和先进的时频信号处理技术，以检查整个大脑的听觉活动；(2)在课堂上学习神经系统的相关细胞和分子生物学以及在紧急振荡活动基础上的神经过程。这些方法和数据将构成R01的基础，旨在使Sz的听觉功能障碍正常化。

DESCRIPTION (provided by applicant): A deficit in the capacity to process auditory information has been proposed as one of the core abnormalities in schizophrenia (Sz). Despite the importance of the subject, we know little about the mechanisms underlying normal or disordered auditory processing, or about the clinical significance of auditory deficits. Research focuses increasingly on the time-frequency brain activity associated with auditory processes, as it's hypothesized that single-trial amplitude and phase measures more closely reflect neural processes. As detailed throughout this K08 proposal, my recent superior temporal gyrus (STG) timefrequency findings build upon and greatly extend findings in this area of research, and present results indicate several clear lines of research where advances in the understanding and treatment of Sz are likely. For the K08 study, using novel tasks developed for this K08 project, functional measures (electroencephalography and magnetoencephalography) of auditory activity throughout the brain will be obtained with 50 controls and 50 patients. There are 3 substantive research goals: (1) determine the nature of auditory abnormalities in Sz by examining multiple nodes in the auditory network and by multiply assessing each processes (encoding vs. gating, amplitude vs. phase-locking), (2) determine whether the abnormal auditory processes can be normalized in patients with Sz by varying attention aI/task-set requirements, and (3) determine the clinical significance of the observed abnormalities. An encoding phase-locking deficit is hypothesized, and it is hypothesized that this abnormality is associated with cognitive problems and increased negative symptoms. K08 training complements K08 research. Primary K08 training goals include: (1) study of several novel distributed source localization methods and advanced time-frequency signal processing techniques in order to examine auditory activity throughout the brain, and (2) classroom work on relevant cellular and molecular biology of the nervous system and the neural processes that underlie emergent oscillatory activity. These methods and data will form the foundation of a R01 that seeks to normalize auditory dysfunction in Sz. PUBLIC HEALTH RELEVANCE: Many individuals with schizophrenia show abnormal brain activity when processing auditory stimuli. We know little about the mechanisms underlying normal or disordered auditory processing. The proposed project uses non-invasive techniques to increase our knowledge of the function of auditory areas in controls and in individuals with schizophrenia. The clinical significance of these abnormalities is also examined.