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，可导致各种症状，从气息到丧失 意识。癫痫的特征是大量神经元的异常放电和 目前的治疗药物无法控制25%的癫痫患者的癫痫发作。我们有 先前表明，一种新的以纤维束(穹隆)为靶点的脑刺激方法，而不是 低频(1-20赫兹)灰质可有效抑制动物模型和 内侧颞叶癫痫(MTLE)患者。我们建议将另一个著名的 抑制大脑皮层癫痫发作的纤维束、穹隆(CC)，并与此进行比较 技术到两种最先进的方法，在高频刺激的焦点 直接或丘脑前核。具体地说，我们建议确定 低频刺激CC可通过选择性地激活中枢神经系统而减少局灶性癫痫发作 急性癫痫模型(目标1)或慢性局灶性癫痫模型中支配病灶的CC纤维 使用破伤风毒素(目标2)。然后，我们建议确定纤维束刺激是否可以改善 多灶刺激与刺激前部刺激对癫痫发作控制的比较 丘脑核团(Aim3)或海人酸组(Aim4)。最后，我们将研究 大鼠大脑皮质脑片体外刺激CC的机制 以前的目标。该项目将在科学家、工程师和 临床医生，如果成功，可能会转化为一种新的针对患者的治疗方式 用于控制顽固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.