Adaptive control of epileptic seizures using a genetically encoded sensor

描述(申请人提供)：约35%的癫痫患者对抗癫痫药物没有反应。在这些患者中，只有四分之一可以通过切除手术进行治疗。患者的癫痫发作源于口才皮质，或者是多灶性、双侧性或全身性的，不适合进行切除手术。对于这些患者，目前可用的一种治疗方法是通过电极进行神经刺激。神经刺激通过操纵遥控系统或干扰致痫区域本身来减少癫痫的发生和传播的可能性。最近的证据表明，人类癫痫发作可以通过适应性(闭环系统)更好地控制，即癫痫发作触发的刺激。这需要 将植入式刺激装置与实时分析技术相结合的复杂装置。事实上，最近的研究表明，患者的闭环刺激有效地降低了癫痫发作的频率和严重程度。然而，这种侵入性方法的缺点是需要植入依赖外部电源的复杂、大型和庞大的电子设备，需要进行重大的、有时是重复的脑部手术，以及实际放置神经刺激电极经常会产生意想不到和不受欢迎的副作用。我们的目标是开发一种替代的，微创的，神经元特异性的治疗策略，以自适应地控制癫痫脑中的神经元放电率。为了测试这项新技术的有效性，我们将使用海人酸实验性癫痫大鼠模型，该模型已被证明产生了类似于人类颞叶癫痫的癫痫综合征。在资助期结束时，我们预计将开发一种新技术，该技术可以彻底改变癫痫治疗策略，并引入一种新的神经科学工具，用于研究与正常大脑功能、其他大脑障碍和神经可塑性相关的神经元网络的活动。

DESCRIPTION (provided by applicant): About 35% of epileptic patients do not respond to antiepileptic drugs. Of these, only a quarter of them can be treated by resective surgery. Patients who have seizures arising from eloquent cortex, or which are multi-focal, bilateral or generalized are not candidates for resective surgery. For these patients, one currently available therapy is neurostimulation via electrodes. Neurostimulation reduces the probability of seizure occurrence and propagation either by manipulating remote control systems or by interfering with the epileptogenic zone itself. Recent evidence suggests that epileptic seizures in humans may be better controlled with adaptive (closed-loop), i.e. seizure-triggered stimulation. This requires a complex setup that integrates an implanted stimulation device coupled with real-time analysis techniques. Indeed, recent studies demonstrate that closed-loop stimulation in patients effectively decrease seizure frequency and severity. However, this invasive approach suffers from the need to implant complex, large and expansive electronic devices which depend on an external power supply, the need for major and sometimes repetitive brain surgeries and the unexpected and undesirable side effects that the actual placement of the neurostimulation electrodes often produces. We aim to develop an alternative, minimally-invasive, neuronal specific therapeutic strategy to adaptively control neuronal firing rates in the epileptic brain. o test the efficacy of this new technology, we will use the kainate acid model of experimental epilepsy in rats that has been demonstrated to produce an epilepsy syndrome similar to human temporal lobe epilepsy. At the end of the funding period we anticipate the development of a novel technology that could revolutionize therapeutic strategies of epilepsy management as well as introduce a new neuroscientific tool for studying the activity of neuronal networks associated with normal brain functions, other brain disorders and neuroplasticity.