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: 7245862
• 负责人: ARTHUR C GRANT
• 金额: $ 10.8万
• 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/7245862
• 关键词: Affect; Antiepileptic Agents; Applications Grants; Area; Auditory; Biological Models; Biometry; Cerebrum; Clinical; Cognition; Conceptions; Data; Dependence; Diffuse; Discrimination; Disease; Disruption; Doctor of Philosophy; Ear; Electroencephalography; Epilepsy; Excision; Experimental Designs; Focal Seizure; Free Will; Frequencies; Functional disorder; Goals; Grant; Hand; Human; Image; Impaired cognition; Impairment; Language; Life; Lobectomy; Measures; Medical; Memory; Mentors; Methodology; Modality; Modeling; Monitor; Nature; Neurology; Noise; Operative Surgical Procedures; Patients; Performance; Pharmaceutical Preparations; Process; Psychophysiology; Qualifying; Recording of previous events; Research Personnel; Seizures; Sensory; Sensory Process; Severities; Signal Transduction; Stimulus; Structure; Syndrome; System; Tactile; Task Performances; Techniques; Temporal Lobe; Temporal Lobe Epilepsy; Testing; Training; Treatment Protocols; Visual; Withdrawal; base; career; cognitive function; cognitive neuroscience; cohort; computerized data processing; improved; network dysfunction; neuroimaging; neurophysiology; patient oriented; professor; programs; sensory system; theories

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）：本申请适用于指导式患者导向RCDA（K23）。候选人接受过临床神经病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的终身助理教授，也是UCI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，通过提出在三种感觉模式中表征精神障碍性早期或“低水平”感知障碍，在医学上难治性（MI）TLE患者，并确定这种受损的皮层处理是否在手术切除致痫区后恢复正常。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。UC Irvine在基础，临床和认知神经科学方面享有盛誉。它还开发了一个忙碌外科临床癫痫计划，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。在这种观点中，发作间期网络内的大脑功能受到发作病灶的影响，即使在没有频繁发作的情况下。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恢复正常。在语言和记忆领域之外，对TLE的认知障碍知之甚少。据推测，多模态知觉功能障碍是目前在颞叶癫痫，这可能是由于短暂中断的正常大脑过程的发作间期“尖峰”起源于癫痫区，它将正常化手术切除后的癫痫发作的重点。40例轻度TLE受试者将接受一系列听觉、触觉和视觉心理物理任务，并将其表现与正常对照组进行比较。任务选择：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负责性能缺陷，2）测试两个类似的能力（主要任务）在所有三种感觉方式，和3）测试早期皮层感觉过程。受试者将在抗癫痫药物（AED）停药后，在有临床指征的连续视频EEG监测期间执行一部分任务，以评估AED对任务表现的影响。然后，受试者将在手术后6个月或初次测试后6个月（对于不符合手术治疗条件的受试者）重新测试所有任务。如果性能改善手术后，没有手术是不变的，如假设，这些结果将有力地支持TLE作为一种网络疾病，其皮质过程的破坏可以逆转手术，但不是药物治疗的概念。