Detection and Control of Epilepsy

描述(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，可导致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，内侧颞叶癫痫(MTLE)是最常见的部分性癫痫。癫痫的特点是大量神经元的异常同步化。目前的治疗药物无法控制25%的癫痫患者的癫痫发作。虽然电刺激大脑对抑制帕金森氏症的一些症状非常有效，但通过脑刺激抑制癫痫的水平一直是有限的。治疗效果低的原因可能是刺激靶点不充分，对机制缺乏了解，刺激参数不是最佳的。在之前的资助期间，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，该方法已经在几个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背后的机制，以改善抑制和指导临床实施。具体地说，我们建议1)揭示抑制和后遗症的细胞机制，2)用光遗传学方法研究抑制神经元的具体作用，3)确定参与抑制的轴突通路。这一神经技术项目的结果将为癫痫抑制的潜在机制提供有价值的见解，并利用之前的赠款期间开发一种控制内侧颞叶癫痫患者癫痫发作的新治疗方法。

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.