An optogenetic brain implant with EEG monitoring and response for mice

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Abstract: Optogenetics can be used to selectively stimulate or suppress the firing of genetically targeted and spatially targeted mammalian neurons. It is used to study neuropsychiatric diseases in vivo with mouse models of conditions including epilepsy, schizophrenia, and Parkinson's. Optogenetics may be used as functional neurosurgical intervention for correcting disease states in the brain. It has been previously shown that seizures have the ability to be halted or reduced by optogenetic activation of inhibitory neurons with the use of Channelrhodopsin-2. It has also been shown that expressing Halorhodopsin (HR) in cortical pyramidal neurons can also reduce seizure propagation. By monitoring EEG data in real time, seizures can be identified at their onset and correcting pulses of optogenetic stimulation may be applied. This line of research is currently limited by the lack of suitable instruments. This project proposes the development of a fully implantable, wireless EEG monitor capable of autonomously detecting EEG events in real-time and applying correcting pulses of closed-loop optogenetic stimulation. The proposed instrument will be compatible with mouse biology, thus permitting chronic experiments in the enormous pool of transgenic mouse strains available with photosensitive proteins and validated as models of human disease. Aim 1 will develop the necessary hardware by combining core technologies demonstrated in existing products. Aim 2 will enable autonomous EEG event detection in the instrument's micropower logic chip by adapting a computationally efficient algorithm that has been proven capable of classifying EEG events including normal activity, seizures, ictal spikes, inter-ictal spikes, and polyspikes. Aim 3 will test the device's ability to detect seizures, apply correcting optogenetic stimulation, and reduce the duration of focal seizures induced in mice by the nanoinjection of iron chloride. Phase I of this project will make the mouse-compatible instrument available for sale to researchers studying circuit theory of the brain and diseases/disorders characterized by aberrant EEG states such as epilepsy, schizophrenia, Alzheimer's, and obsessive compulsive disorder. Potential follow-on Phase II would develop the technology into a medical instrument that aborts focal seizures in humans who suffer from pharmaceutical-resistant partial epilepsy (approximately 15 million people).