Effect of temporal lobectomy on sensory deficits in TLE

颞叶切除术对 TLE 感觉缺陷的影响

• 批准号: 6898754
• 负责人: ARTHUR C GRANT
• 金额: $ 14.71万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6898754
• 关键词: anticonvulsants; auditory stimulus; behavioral /social science research tag; clinical research; electroencephalography; electrophysiology; human subject; human therapy evaluation; nervous system disorder therapy; neural information processing; neuropsychological tests; neurosurgery; partial seizure; patient oriented research; perception disorder; psychophysics; sensory signal detection; statistics /biometry; temporal lobe /cortex disorder; video recording system; visual stimulus

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.

描述(由申请人提供)：本申请是一份以患者为导向的辅导型RCDA(K23)。应聘者受过临床神经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学终身教授，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使用心理物理、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这一过程的第一步，通过提议对医学上难治性(Mi)TLE患者的三种感觉形式的心理生理早期或低水平的知觉障碍进行表征，并确定这种受损的皮质处理在手术切除致痫区域后是否恢复正常。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)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领域享有盛誉。它还开发了一个繁忙的外科临床癫痫课程，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，而不是孤立的病理上与致痫灶有关的疾病。这种观点认为，发作间期网络内的大脑功能受到发作灶的影响，即使在没有频繁发作的情况下也是如此。这一理论的临床意义重大，包括这种脑功能障碍可能通过手术治疗恢复正常的可能性。在语言和记忆领域之外，人们对TLE中的认知障碍知之甚少。推测癫痫患者存在多模式知觉障碍，可能是发作间歇期起源于致痫区的“棘波”对正常脑过程的一过性干扰所致，经手术切除癫痫灶后可恢复正常。40名轻度癫痫患者将接受一系列听觉、触觉和视觉心理物理任务，并与正常对照组进行比较。任务选择的目的是：1)确定刺激持续时间对任务绩效的影响。这应该是一个关键因素，如果发作间期尖峰是造成操作缺陷，2)测试两个类似的能力(主要任务)在所有三种感觉模式，和3)测试早期皮质感觉过程。受试者将在临床指示的持续视频脑电监测期间，在停用抗癫痫药物(AED)后执行任务的子集，以评估AED对任务绩效的影响。然后，受试者将在手术后6个月重新接受所有任务的测试，对于那些没有资格接受手术治疗的人，则在初次测试6个月后进行重新测试。如果手术后表现改善，而没有手术的情况下没有变化，这些结果将有力地支持TLE是一种网络性疾病的概念，其皮质过程的中断可以通过手术而不是内科治疗来逆转。