Closed-loop distributed microstimulation for epilepsy

描述（由申请人提供）： 癫痫是数百万美国人的一种使人衰弱的疾病，许多人没有得到药物或切除手术的帮助。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完全被来自一系列小电极的低电流、低频率刺激所阻断。同时记录神经活动并用它来改变刺激电压也就是说，使用闭环反馈来控制刺激允许甚至更低的电压和更慢的频率来阻止类似神经元的事件。目前的提议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。具体而言，它建议调查参数在体内有效的微刺激（使用定制的刺激器和记录套件），在正常和癫痫的大脑，并试图抑制癫痫样活动在体内与分布式刺激和闭环刺激。最后，由于所提出的方法依赖于记录的动作电位从多个单独的细胞，它被建议调查的关系，这个单细胞活动的经典癫痫发作措施，脑电图（EEC），沿着与当地的场电位记录从高阻抗微丝。该方法使用32通道的微丝阵列，长期植入成年大鼠的大脑皮层或感觉运动皮层，在同一区域微量注射破伤风毒素致癫痫。该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EEG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：许多癫痫患者继续经历癫痫发作，尽管我们有最好的药物治疗。我们的实验室已经证明，用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。该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，然后再开始临床试验。

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.