Adaptive Control of Epileptic Seizures Using A Genetically Encoded Sensor

Principal Investigator: Galit Pelled

Sponsored by the National Institutes of Health (NIH) -- 1R01NS079288-01.

About 35 percent 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. To 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.

PUBLIC HEALTH RELEVANCE: Epilepsy is a common chronic neurological disorder that affects 0.5-1 percent of the population. We aim to develop a novel, minimally-invasive, neuronal specific therapeutic strategy to adaptively control neuronal firing rates in the epileptic brain. To test the efficacy of this new technology, we will use an animal model of experimental epilepsy that has been demonstrated to produce an epilepsy syndrome similar to human temporal lobe epilepsy.