Distributed microstimulation for epilepsy

描述(由申请者提供)：摘要尽管有最好的内科和外科治疗方法，但癫痫发作仍困扰着100多万美国人。人们迫切需要新的疗法。我们已经在生物医学工程师和翻译临床科学家之间形成了富有成效的合作，开创了一种新的方法，通过直接闭合环多电极微刺激癫痫灶来抑制癫痫发作的产生。该方法是基于我们的兴奋的体外工作，在该工作中，神经元培养中的癫痫样活动被分布在多个电极上的低电压、低频微刺激完全阻断。本项目的目标是在活体内翻译这些结果。我们已经制造了一种新的定制设计的系统，可以同时以闭环反馈的方式刺激和记录长期植入的微电极。我们将优化参数和材料，以有效地将癫痫灶内神经元的放电率维持在防止癫痫发作背后的动作电位爆发的范围内。我们的成功将通过在局灶性发作的大鼠模型中展示脑电(EEG)和行为发作活动的调节来衡量。如果成功，这项工作将为因难治性局灶性癫痫发作而致残的患者带来一种新的治疗方法。公共卫生相关性：为了治疗难治性局灶性癫痫发作，我们提出了一种新的方法，通过微电极阵列将电刺激持续传递到癫痫灶，以保持神经活动在不会引起癫痫发作的范围内。在这种方法中，基于我们在细胞培养模型中完全抑制癫痫样动作电位爆发的能力，状态控制方法防止癫痫发作的发生，而不是试图在癫痫发作发生后中止癫痫发作。这项在啮齿性局灶性癫痫模型中的转化研究有望为致残性、难治性局灶性癫痫发作患者带来亟需的新疗法。

DESCRIPTION (provided by applicants): Abstract Uncontrolled epileptic seizures plague more than one million Americans, despite the best medical and surgical treatments available. Novel therapies are desperately needed. We have formed a productive collaboration between a biomedical engineer and a translational clinician-scientist to pioneer a novel approach to suppressing generation of seizures using direct closed-loop multielectrode microstimulation of the epileptic focus. The method is based on our exciting in vitro work in which epileptiform activity in neuronal cultures was completely blocked by low voltage, low frequency microstimulation, distributed across multiple electrodes. The goal of the present project is to translate these results in vivo. We have manufactured a novel custom-designed system to simultaneously stimulate and record from chronically implanted microelectrodes in a closed-loop feedback fashion. We will optimize the parameters and materials to effectively maintain the firing rate of neurons in the epileptic focus in a range from which bursts of action potential - which underlie epileptic seizures - are prevented from occurring. Our success will be measured by demonstrating modulation of electrographic (EEG) and behavioral seizure activity in our rat model of focal onset seizures. If successful, this work will lead to a new treatment for patients disabled by intractable focal onset seizures. PUBLIC HEALTH RELEVANCE: To treat intractable focal-onset epileptic seizures, we propose a novel approach in which electrical stimulation - continuously delivered to the epileptic focus through arrays of microelectrodes - is tuned to maintain neural activity in a range from which epileptic seizures cannot arise. In this approach, which is based on our ability to completely suppress epileptiform bursts of action potentials in a cell culture model, state-control methodology prevents seizures from arising, rather than attempting to abort seizures after they arise. This translational research in a rodent focal epilepsy model hopefully will lead to a much needed novel treatment for patients with disabling, intractable focal-onset seizures.