3D multifunctional deep brain interface for seizure detection and intervention

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Project Summary/Abstract: Treatment of neurological disorders and psychiatric diseases, such as epilepsy, remains a big clinical challenge in large populations of patients. A fundamentally more effective treatment method requires a thorough understanding of the functional networks in the brain. This endeavor, however, critically relies on the engineering success of building a deep brain interface that mimics brain complexity and is also compatible with brain tissues. A key challenge in current neural interface devices is to map and modulate the brain dynamics over a large volume in deep brain while providing a high spatiotemporal resolution and maintaining minimal tissue damage. Our primary goal is to address this challenge by developing a spatially expandable fiber-based neural probe as a multifunctional deep brain interface. The central hypotheses in this project are: (1) The spatially expandable fiber-based probe arrays can provide a minimally invasive 3D interface to achieve biomechanical and biochemical compatibility with brain tissue, as well as to enable large volume stimulation and recording with a high spatiotemporal resolution; (2) The probe arrays allow for more precise detection of seizure foci compared with existing methods, and enable real time suppression of seizure activities by localized optogenetic and drug regulation. The specific aims of this project are: (1) Develop spatially expanded fiber-based probe arrays for multifunctional in vivo neural interfacing; (2) Elucidate the electrical recording, optical stimulation, and drug delivery performance of the probe arrays in vivo and the tissue response of the probe arrays; (3) Demonstrate seizure foci detection and real-time seizure suppression using localized drug and optogenetic intervention in deep brain. The hypotheses and aims will be tested using a clinically relevant animal model of virus-induced seizure in mouse employing a combination of electrophysiology, optogenetics, and focal drug delivery in vivo, as well as imaging and histology in brain slices. This technology can provide a powerful tool for advancing the fundamental study of the microcircuitry and functional networks in both animal and human brains. In the future, these studies have the potential to elucidate novel ways to detect and treat neurological diseases at an early stage and more effectively compared to other existing methods.