Adaptive control of epileptic seizures using a genetically encoded sensor

描述（由申请人提供）：约35%的癫痫患者对抗癫痫药物无反应。其中，只有四分之一可以通过切除手术治疗。由雄辩皮质引起的癫痫发作，或多灶性、双侧或全身性癫痫发作的患者不适合切除手术。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。通过操纵遥控系统或干扰致痫区本身，神经刺激可减少癫痫发作和传播的可能性。最近的证据表明，采用适应性（闭环）刺激，即癫痫触发刺激，可以更好地控制人类癫痫发作。这需要

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.