Distributed microstimulation for epilepsy

描述（由申请人提供）：摘要不受控制的癫痫发作困扰超过一百万美国人，尽管最好的医疗和手术治疗。迫切需要新的治疗方法。我们已经形成了一个生物医学工程师和翻译临床科学家之间的富有成效的合作，开拓了一种新的方法来抑制癫痫发作的产生，使用直接闭环多电极微刺激癫痫灶。该方法基于我们令人兴奋的体外工作，其中神经元培养物中的癫痫样活动被分布在多个电极上的低压、低频微刺激完全阻断。本项目的目标是在体内转化这些结果。我们已经制造了一种新颖的定制设计的系统，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，以有效地保持癫痫病灶中神经元的放电率在一定范围内，从而防止癫痫发作的动作电位爆发。我们的成功将通过在我们的局灶性发作癫痫大鼠模型中证明电图（EEG）和行为癫痫发作活动的调制来衡量。如果成功，这项工作将为因顽固性局灶性发作癫痫而致残的患者带来新的治疗方法。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，其中电刺激-通过微电极阵列连续传递到癫痫病灶-被调谐以维持癫痫发作不能出现的范围内的神经活动。在这种方法中，这是基于我们的能力，完全抑制癫痫样爆发的动作电位在细胞培养模型中，状态控制方法防止癫痫发作的发生，而不是试图中止癫痫发作后，他们出现。这项在啮齿类动物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.