Effect of temporal lobectomy on sensory deficits in TLE

描述（由申请人提供）：本申请是指导患者导向的RCDA （K23）。该候选人接受过临床神经病学和神经生理学的培训，并完成了基础视觉神经生理学的博士论文。他是加州大学欧文分校神经病学的终身助理教授，也是加州大学欧文分校综合癫痫项目的副主任。候选人的长期职业目标是利用心理物理，成像和电生理技术研究皮层网络功能和功能障碍，最初使用颞叶癫痫（TLE）作为模型系统。这项拨款申请代表了这一过程的第一步，通过提出在医学难治性（mi） TLE患者的三种感觉模式中表征心理物理早期或“低水平”感知障碍，并确定这种受损的皮层处理是否在手术切除致痫区后正常化。该提案的培训部分强调三个方面：1)网络理论及其在人类感觉系统中的应用，2)临床实验设计和生物统计学，以及3)心理物理感知任务的方法和应用。加州大学欧文分校在基础、临床和认知神经科学方面享有良好声誉。它还开发了一个繁忙的外科临床癫痫项目，因此非常适合候选人的职业目标。有有限但令人信服的证据表明，TLE是一种网络疾病，而不是孤立的病理致痫灶。在这种观点下，即使在没有频繁发作的情况下，神经网络内的间歇期脑功能也会受到发作灶的影响。这一理论的临床意义是重要的，包括这种脑功能障碍可能通过手术治疗正常化。在语言和记忆领域之外，人们对颞叶痴呆的认知障碍知之甚少。据推测，多模态知觉功能障碍存在于TLE中，它可能是由起源于癫痫区的间歇“尖峰”对正常大脑过程的短暂中断造成的，并将在手术切除癫痫病灶后恢复正常。40名患有轻度TLE的受试者将接受一系列听觉、触觉和视觉心理物理任务，并将他们的表现与正常对照进行比较。选择任务的目的是：1)确定刺激持续时间对任务绩效的影响。如果间歇尖峰是导致表现缺陷的原因，这应该是一个关键因素，2)测试所有三种感觉模式的两种类似能力（主要任务），3)测试早期皮层感觉过程。在临床指示的连续视频脑电图监测期间，受试者将在停药后执行部分任务，以评估AED对任务表现的影响。然后在手术后6个月对受试者进行所有任务的重新测试，对于不符合手术治疗条件的受试者，在初始测试后6个月进行重新测试。如果像假设的那样，手术后的表现有所改善，而不手术也没有变化，那么这些结果将有力地支持TLE作为一种网络疾病的概念，其皮质过程的破坏可以通过手术逆转，而不是药物治疗。

DESCRIPTION (provided by applicant): This application is for a Mentored Patient-Oriented RCDA (K23). The candidate is trained in clinical neurology and neurophysiology, and completed a Ph.D. thesis in basic visual neurophysiology. He is a tenure track Assistant Professor of Neurology at UC Irvine, and Associate Director of the UCI comprehensive epilepsy program. The candidate's long-term career goal is to study cortical network function and dysfunction using psychophysical, imaging, and electrophysiologic techniques, initially using temporal lobe epilepsy (TLE) as a model system. This grant application represents the first step in that process, by proposing to characterize psychophysically early or "low-lever' perceptual impairments in three sensory modalities in patients with medically intractable (mi) TLE, and to determine if such impaired cortical processing normalizes after surgical removal of the epileptogenic zone. The training portion of the proposal emphasizes three areas: 1) Network theory and its application to human sensory systems, 2) clinical experimental design and biostatistics, and 3) methodology and application of psychophysical perceptual tasks. UC Irvine has a proven reputation in basic, clinical and cognitive neuroscience. It also has developed a busy surgical clinical epilepsy program, and is thus ideally suited to the candidate's career goals. There is limited but compelling evidence that TLE is a network disease, not isolated pathologicallyto the epileptogenic focus. In this view, interictal cerebral function within the network is affected by the seizure focus, even in the absence of frequent seizures. Clinical implications of this theory are significant, and include the possibility that such cerebral dysfunction may normalize with surgical treatment. Outside the domains of language and memory, little is known of cognitive impairments in TLE. It is hypothesized that multi-modal perceptual dysfunction is present in mi TLE, that it may result from transient disruption of normal cerebral processes by interictal "spiking" originating in the epileptogenic zone, and that it will normalize after surgical removal of the seizure focus. Forty subjects with mi TLE will undergo a battery of auditory, tactile and visual psychophysical tasks, and their performance compared to normal controls. Tasks were chosen to: 1) Determine the effect of stimulus duration on task performance. This should be a critical factor if interictal spiking is responsible for performance deficits, 2) test two analogous abilities (primary tasks) in all three sensory modalities, and 3) test early cortical sensory processes. Subjects will perform a subset of the tasks after anti-epileptic medication (AED) withdrawal during clinically indicated continuous video-EEG monitoring to assess the effect of AEDs on task performance. Subjects will then be retested on all tasks 6 months after surgery, or 6 months after initial testing for those who do not qualify for surgical treatment. If performance improves after surgery and is unchanged without surgery, as is hypothesized, these results would strongly support the notion of TLE as a network disease whose disruption of cortical processes could be reversed with surgical, but not medical treatment.