Closed-loop distributed microstimulation for epilepsy

描述(由申请人提供)： 癫痫对数百万美国人来说是一种令人衰弱的疾病，许多人在药物治疗或切除手术中得不到帮助。需要新的治疗方法。史蒂夫·波特博士的实验室最近表明，神经元培养中的癫痫活动可以被一系列小电极的低电流、低频率刺激完全阻断。同时记录神经活动并用它来修改刺激电压--也就是使用闭环反馈控制刺激--允许更低的电压和更慢的频率来阻止癫痫样事件。目前的提案将把这些发现扩展到患有慢性自发癫痫的活体啮齿动物。具体地说，它被建议在正常和癫痫脑中研究有效的体内微刺激的参数(使用定制的刺激器和记录套件)，并试图通过分布式刺激和闭合环刺激来抑制体内的癫痫样活动。最后，由于该方法依赖于记录的多个单个细胞的动作电位，因此建议研究这种单个细胞的活动与经典的惊厥测量脑电(EEC)以及从高阻抗微丝记录的局部场电位的关系。该方法使用32通道微线阵列，长期植入成年大鼠的海马区或感觉运动皮质，在同一区域微量注射破伤风毒素，使癫痫发作。这些阵列记录了啮齿动物慢性自发癫痫发作期间的细胞动作电位和脑电样场电位。定制的刺激器允许从同一组植入的电极同时进行记录和刺激。 公共卫生相关性：尽管我们采取了最好的治疗方法，但许多癫痫患者仍持续发作。我们的实验室已经证明，通过状态控制算法记录和刺激的小电极阵列，可以完全抑制培养的脑组织中的癫痫活动。这项提案将在癫痫动物模型中研究这种治疗方法，以验证其安全性和有效性，然后开始临床试验。

DESCRIPTION (provided by applicant): Epilepsy is a debilitating disorder for millions of Americans, and many are not helped with medications or resective surgery. New therapies are needed. The laboratory of Dr. Steve Potter has recently shown that epileptic activity in neuronal cultures is completely blocked by low-current, low-frequency stimulation from an array of small electrodes. Simultaneously recording neural activity and using it to modify stimulation voltages-that is, using closed-loop feedback to control stimulation-allowed even lower voltages and slower frequencies to block the seizure-like events. The current proposal will extend these findings to live rodents with chronic, spontaneous seizures. Specifically, it is proposed to investigate parameters for effective microstimulation in vivo (using a custom-built stimulator and recording suite), in both normal and epileptic brains, and attempt to suppress epileptiform activity in vivo with both distributed stimulation and closed-loop stimulation. Lastly, since the proposed method relies on recorded action potentials from multiple individual cells, it is proposed to investigate the relation of this single cell activity to the classical seizure measure, the electroencephalogram (EEC), along with local field potentials recorded from high impedance microwires. The methodology uses 32-channel microwire arrays, chronically implanted in the hippocampi or sensorimotor cortex of adult rats, made epileptic with microinjections of tetanus toxin in the same region. The arrays record both cellular action potentials and EEG-like field potentials during the chronic, spontaneous seizures the rodents exhibit. A custom-built stimulator allows simultaneous recording and stimulation from the same implanted set of electrodes. PUBLIC HEALTH RELEVANCE: Many patients with epilepsy continue to experience seizures despite our best medical therapies. Our lab has shown that small arrays of electrodes, recording and stimulating with a state-control algorithm, can completely suppress epileptic activity in cultured brain tissue. This proposal will investigate this treatment in animal models of epilepsy, to validate its safety and efficacy, before beginning clinical trials.