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。癫痫患者反复发作，可引起各种症状，从肌肉僵硬到意识丧失。部分性癫痫是成人癫痫患者中最常见的综合征，而内侧颞叶癫痫（MTLE）是部分性癫痫最常见的形式。癫痫的特点是大量神经元异常同步。目前的治疗药物不能控制25%的癫痫患者的癫痫发作。虽然脑电刺激对抑制帕金森病的某些症状非常有效，但脑电刺激对癫痫发作的抑制程度有限。这种低治疗效果的原因可能是刺激靶点不充分，缺乏对机制的理解和非最佳刺激参数。在之前的资助期间，我们开发了一种通过激活低频纤维束靶点来抑制癫痫发作的新方法，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。我们建议研究这种强大的抑制方法的机制，以改善抑制和指导临床实施。具体而言，我们建议1)阐明抑制的细胞机制和后效，2)利用光遗传学方法研究抑制性神经元的具体作用，3)确定参与抑制的轴突通路。这项神经技术项目的结果将为癫痫发作抑制的机制提供有价值的见解，并利用先前的资助期开发一种新的治疗方法来控制内侧颞叶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.