Detection and Control of Epilepsy

描述（由申请人提供）：癫痫是最常见的神经系统疾病之一。 癫痫患者经历反复发作，可引起从肌肉僵硬到意识丧失的各种症状。 部分性癫痫是成人癫痫患者最常见的综合征，而内侧颞叶癫痫（MTLE）是部分性癫痫最常见的形式。 癫痫的特征是大量神经元的异常同步。 目前的治疗药物不能控制所有癫痫患者中25%的癫痫发作。 虽然电刺激大脑已经非常有效地抑制帕金森病的一些症状，但通过脑刺激抑制癫痫发作的水平有限。 这种低治疗结果的原因可能是刺激靶点不足、缺乏对机制的理解和非最佳刺激参数。 在上一个资助期间，我们开发了一种新的方法，通过激活低频率的纤维束靶点来抑制癫痫发作，该方法已在几种动物模型和内侧颞叶癫痫患者中进行了测试。 我们现在建议研究这种强大的抑制方法的机制，以提高抑制和指导临床实施。 具体而言，我们建议1）解开抑制和后效应的细胞机制，2）使用光遗传学方法研究抑制性神经元的特定作用，3）确定参与抑制的轴突通路。 这个神经技术项目的结果应该提供有价值的见解癫痫发作抑制的机制，以及利用以前的补助金期间开发一种新的治疗方法，用于控制颞叶内侧癫痫患者的癫痫发作。

DESCRIPTION (provided by applicant): Epilepsy is one of the most prevalent neurological disorders. Patients with epilepsy experience recurrent seizures that can cause a variety of symptoms ranging from muscle stiffness to loss of consciousness. Partial epilepsy is the most common syndrome in adult epilepsy patients and mesial temporal lobe epilepsy (MTLE) is the most common form of partial epilepsy. Epilepsy is characterized by the abnormal synchronization of large numbers of neurons. Current therapeutic agents cannot control seizures in 25% of all epileptic patients. Although electrical stimulation of the brain has been very effective to suppress some symptoms of Parkinson's disease, the level of seizure suppression by brain stimulation has been limited. The reason for this low therapeutic outcome could be attributed to an inadequate target for stimulation, lack of understanding of the mechanisms and non-optimum stimulation parameters. During the previous grant period, we have developed a novel method to suppress seizures by activating a fiber tract target at low frequency that has been tested in several animal models and in patients with mesial temporal lobe epilepsy. We now propose to study the mechanisms underlying this powerful suppression method in order to improve the suppression and guide the clinical implementation. Specifically, we propose to 1) unravel the cellular mechanisms of the suppression and the after effects, 2) study the specific role of inhibitory neurons using optogenetics methodology and 3) determine the axonal pathways involved in the suppression. The results of this neuro-technology project should provide valuable insights into the mechanisms underlying seizure suppression as well as capitalizing on the previous grant period to develop a novel therapeutic method for the control of seizures in patients with mesial temporal lobe epilepsy.