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使人衰弱的疾病，许多人无法通过药物或切除手术得到帮助。需要新的疗法。史蒂夫·波特博士的实验室最近表明，神经元培养物中的癫痫活动可以被一系列小电极的低电流、低频刺激完全阻断。同时记录神经活动并用它来修改刺激电压——即使用闭环反馈来控制刺激——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性癫痫发作的活体啮齿动物。具体来说，建议研究正常大脑和癫痫大脑中有效体内微刺激的参数（使用定制的刺激器和记录套件），并尝试通过分布式刺激和闭环刺激抑制体内癫痫样活动。最后，由于所提出的方法依赖于记录的多个单个细胞的动作电位，因此建议研究该单细胞活动与经典癫痫测量、脑电图（EEC）以及从高阻抗微线记录的局部场电位的关系。该方法使用 32 通道微丝阵列，长期植入成年大鼠的海马体或感觉运动皮层，通过在同一区域显微注射破伤风毒素使其癫痫发作。该阵列记录了啮齿类动物表现出的慢性自发癫痫发作期间的细胞动作电位和脑电图样场电位。定制的刺激器允许从同一组植入的电极同时记录和刺激。 公共卫生相关性：尽管我们提供了最好的药物治疗，许多癫痫患者仍然会出现癫痫发作。我们的实验室已经证明，通过状态控制算法进行记录和刺激的小型电极阵列可以完全抑制培养脑组织中的癫痫活动。该提案将在开始临床试验之前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。

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.