Low-frequency stimulation of fiber tracts to control seizures

摘要 癫痫是最常见的神经系统疾病之一。癫痫患者的经历 反复发作，可引起各种症状，从先兆到丧失 意识癫痫的特征是大量神经元的异常放电， 目前的治疗剂不能控制所有癫痫患者中25%的癫痫发作。我们有 以前表明，一种新的脑刺激方法，目标是纤维束（穹窿），而不是 低频（1- 20 Hz）的灰质在动物模型中有效抑制癫痫发作， 内侧颞叶癫痫（MTLE）患者。我们建议以另一个著名的 纤维束，胼胝体（CC）抑制皮质癫痫发作，并比较这一点， 技术的两个国家的最先进的方法，刺激在高频率或重点 直接或丘脑前核。具体而言，我们建议确定， 低频刺激CC可以通过选择性激活 在急性模型（Aim 1）或局灶性慢性癫痫模型中支配病灶的CC纤维 破伤风毒素（目标2）。然后，我们建议确定纤维束刺激是否可以改善 与刺激前部相比，由多个病灶产生的活动的癫痫发作控制 丘脑核（Aim 3）或在慢性模型中与红藻氨酸（Aim 4）。最后，我们将研究 使用从动物中获得的体外皮质脑切片研究CC刺激的机制， 以前的目标。该项目将由科学家、工程师和 临床医生，如果成功，可以转化为一种新的患者特异性治疗方式 用于控制难治性癫痫患者的皮质癫痫发作。

Abstract Epilepsy is one of the most prevalent neurological disorders. Patients with epilepsy experience recurrent seizures that can cause a variety of symptoms ranging from auras to loss of consciousness. Epilepsy is characterized by the abnormal firing of large numbers of neurons and current therapeutic agents cannot control seizures in 25% of all epileptic patients. We have previously shown that a novel brain stimulation method targeting fiber tracts (fornix) instead of grey matter at low frequency (1-20Hz) is effective to suppress seizures in animal models and patients with mesial temporal lobe epilepsy (MTLE). We propose to target another prominent fiber tract, the corpus callosum (CC) to suppress cortical seizures and to compare this technology to two state-the-art methods that stimulate at high frequency either the focus directly or the anterior nucleus of the thalamus. Specifically, we propose to determine if stimulation of the CC at low frequency can decrease focal seizures by selectively activating the CC fibers innervating the focus in an acute model (Aim 1) or in focal chronic model of epilepsy with tetanus toxin (Aim 2). We then propose to determine if fiber tract stimulation can improve seizure control of activity generated by multiple foci compared to stimulation of the anterior nucleus of the thalamus (Aim3) or with kainic acid in chronic model (Aim4). Finally, we will study the mechanisms of the CC stimulation using in-vitro cortical brain slices obtained from animals in previous aims. The project will be carried with a collaboration between scientists, engineers and clinicians and if successful could be translated into a novel patient-specific therapeutic modality for the control of cortical seizures in patients with intractable epilepsy.