Effect of temporal lobectomy on sensory deficits in TLE

描述（由申请人提供）：本申请适用于指导性患者导向 RCDA (K23)。该候选人接受过临床神经学和神经生理学培训，并完成了博士学位。基础视觉神经生理学论文。他是加州大学欧文分校神经病学终身教授助理教授，也是加州大学尔湾分校综合癫痫项目的副主任。候选人的长期职业目标是使用心理物理学、成像和电生理学技术研究皮质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该过程的第一步，提出对医学上难治性 (mi) TLE 患者的三种感觉模式的心理物理早期或“低度”知觉损伤进行表征，并确定在手术切除致痫区后这种受损的皮质处理是否正常化。该提案的培训部分强调三个领域：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)加州大学欧文分校在基础、临床和认知神经科学方面享有盛誉，因此非常适合候选人的职业目标。有限但令人信服的证据表明，TLE 是一种网络疾病，在病理上并非孤立于癫痫病灶，即使没有频繁的癫痫发作，网络内的发作间期脑功能也会受到影响。除了语言和记忆领域外，这种脑功能障碍可能会通过手术治疗而恢复正常。据推测，mi TLE 中存在多模式知觉功能障碍，这可能是由于癫痫发作区的发作间期“尖峰”对正常大脑过程的短暂破坏造成的，并且在手术切除癫痫病灶后，该功能将恢复正常。选择触觉和视觉心理物理任务，以及与正常对照相比的表现，以：1）确定刺激持续时间对任务表现的影响，如果发作间期尖峰是导致表现缺陷的关键因素，2）测试所有三种感觉模式中的两种类似能力（主要任务），以及3）测试早期皮质感觉过程。然后，将在手术后 6 个月或在初次测试后 6 个月对受试者进行视频脑电图监测，以评估 AED 对任务表现的影响。如果如假设的那样，手术后表现有所改善并且在不进行手术的情况下没有变化，那么这些结果将有力地支持 TLE 作为一种网络疾病的概念，其对皮质过程的破坏可以通过手术而非药物治疗来逆转。

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.