Distributed microstimulation for epilepsy

描述（由申请人提供）：摘要尽管有最好的医疗和手术治疗，但仍有超过一百万的美国人患有无法控制的癫痫发作。迫切需要新的治疗方法。我们已经在一位生物医学工程师和一位转化临床医生科学家之间形成了富有成效的合作，以开拓一种新的方法，通过对癫痫病灶进行直接闭环多电极微刺激来抑制癫痫发作的产生。该方法是基于我们激动人心的体外实验，在实验中，分布在多个电极上的低压、低频微刺激完全阻断了神经元培养物中的癫痫样活动。目前项目的目标是在体内转化这些结果。我们制造了一种新颖的定制设计系统，以闭环反馈方式同时刺激和记录长期植入的微电极。我们将优化参数和材料，以有效地维持癫痫灶中神经元的放电速率，在一定范围内防止动作电位的爆发-这是癫痫发作的基础-发生。我们的成功将通过在我们的局灶性癫痫大鼠模型中展示电图（EEG）和行为癫痫活动的调制来衡量。如果成功，这项工作将为顽固性局灶性癫痫致残患者提供一种新的治疗方法。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，即电刺激-通过微电极阵列连续传递到癫痫病灶-调整以维持神经活动在癫痫发作不会发生的范围内。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，而不是试图在癫痫发作后中止癫痫发作。这项在啮齿动物局灶性癫痫模型中的转化研究有望为致残、难治性局灶性癫痫患者提供急需的新治疗方法。

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.