Implantable Neurostimulators for Control of Oscillatory Brain Networks

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We propose to develop an implantable brain stimulation system to measure and control oscillatory local field potential (LFP) synchrony within brain networks. Implantable neurotechnologies like deep brain stimulation (DBS) have revolutionized the treatment of movement disorders and epilepsy. DBS has some clinical signal in psychiatry as well, but individual trial results are highly variable. We have argued that this is a target engagement problem – that the high-frequency constant stimulation used in Parkinson’s or other tremor disorders is not the right approach to the circuits of mental illness. Instead, we believe the correct approach is to identify signatures of healthy communication in these circuits/networks, then design stimulation protocols that specifically produce those signatures. LFP synchrony is likely one of those communication signatures. Across multiple domains of cognitive and emotional function, behavioral performance (a read-out of successful network communication) improves when brain regions show synchronous (coherent) LFP oscillations. Further, clinically effective DBS, in movement and psychiatric disorders, is associated with changes in LFP synchrony. Co-PI Widge has developed algorithms that specifically control inter-regional LFP synchrony, by locking electrical stimulation pulses in one region to the phase of an ongoing oscillation in another region. The translational challenge is that efficient, implantable real-time synchrony monitoring and phase-locked stimulation require signal processing capabilities not found in any existing or anticipated device. Co-PI Shoaran has developed power-efficient phase estimation circuits, specifically optimized for DBS- like implants. We propose to combine these approaches. Aims 1 and 2 will develop a new application- specific integrated circuit (ASIC) that integrates Dr. Shoaran’s measurement and neural decoding frameworks with Dr. Widge’s oscillation-control methods. We will validate this circuit’s recording and phase-locking capabilities in vivo in Dr. Widge’s rodent lab. In Aim 3, a world-leading contract implant manufacturer (Cirtec) will integrate that new ASIC into a packaged, implant-ready device ready for large animal safety testing. Cirtec has already developed a DBS prototyping platform optimized to get new therapies more quickly into first-in- human, allowing us to greatly accelerate the path to the clinic and reduce regulatory risk. At the end of 5 years, we will either be ready for that clinical pilot or have only modest safety testing remaining. Our team has expertise in electronics, medical device fabrication, clinical brain stimulation, and technology commercialization. The work will be headquartered in Minnesota’s “Medical Alley”, an epicenter of medical device innovation. We are well-qualified to execute these Aims and bring the resulting technology to market. Success would yield a new implant optimized for network monitoring and therapy, a powerful new tool for both psychiatric treatment and cutting-edge neuroscience research.