NCS-FO: Fully Wireless Flexible Electrical-Acoustic Implant for High-Resolution Neural Stimulation and Recording at Large Scale

Dynamic mapping of complex brain circuits by monitoring and modulating brain activity can enhance our understanding of brain functions and provide the promise of better treatment and prevention of different neurological disorders. Interfacing with the brain also has the potential to enhance our perceptual, motor, and cognitive capabilities, as well as to restore sensory and motor functions lost through injuries or diseases. The development of closed-loop neural interfaces with high-resolution recording and stimulation capabilities from the distributed neural circuits within the entire brain is still a grand challenge of neuroscience research. Current noninvasive neuromodulation techniques still suffer from poor spatial resolution (> 100-1000’s of mm3), while implantable methods with finer resolution only provide a limited coverage of 100-1000’s of neurons through highly invasive parenchymal implantation. This integrated research and education program enables minimally invasive ultrasound neuromodulation (and neural recording) of the brain with high spatial resolution (< 200 µm) at large scale (over the whole brain). This project will yield a unique building block for a comprehensive set of neural interfaces. It will open new opportunities in neuroscience with significant improvements in spatial resolution and coverage of the brain stimulation in animals. It will also have translational potential for clinical applications in humans, such as the treatment of neurological and psychiatric disorders and brain-machine interfaces. This project also includes an integrated outreach and educational component to impact K-12 teachers and students (particularly from underrepresented groups), minorities, and undergraduate and graduate students, and to develop an interdisciplinary workforce. This project will educate a broad audience (particularly women) in the science and applications of the research components and enhance their research skills through systematic troubleshooting activities. Graduate curriculums across different disciplines will also be transformed with related multidisciplinary projects and guest lectures.This project includes scientific research to investigate implantable ultrasound stimulation on a flexible platform (placed on the brain surface with no parenchymal penetration) to simultaneously provide high spatial resolution (< 200 µm) and broad coverage (over the whole brain) while dramatically reducing invasiveness. This multidisciplinary project, which brings together expertise in electrical and biomedical engineering as well as material, computer, and neuro science, is transformative in that it is potentially the only method that promises large-scale stimulation across distributed brain regions at different depths with high resolutions of < 200 µm without parenchymal implantation, opening a new venue for understanding neural and cognitive systems at large temporal and spatial scales. The development of this technology builds upon investigators’ strength in circuits, wireless power, flexible technologies, thin-film ultrasound arrays, machine learning, and neural interfaces. The project pushes the limits of ultrasound neuromodulation by investigating a flexible, image-guided (with machine learning models), hybrid electrical-acoustic implantable system with the form factor of a thin flexible sheet (on the brain surface) for ultrasound stimulation (and electrophysiology recording). Three fundamental research gaps will be addressed. 1) For large-scale and high-resolution ultrasound beam focusing and steering, the optimal approach in scaling up the number of ultrasound elements and application-specific integrated circuit (ASIC) channels at high frequencies (e.g., 5 MHz) will be explored. To reduce the complexity, thin-film transistors on a flexible substrate will be leveraged to form a large two-dimensional ultrasound array with selectable one-dimensional arrays (e.g., 256-element) driven by only one ASIC. 2) Selectable thin-film ultrasound arrays with thin-film transistor switches on flexible substrate will be optimized to achieve high efficiency and high pressure output. 3) Imaging and machine learning models based on image sequence analysis will be developed to guide the ultrasound focused beam, considering the device flexibility (ultrasound elements’ orientation) and post-implantation effects. A system-level demonstration in benchtop and in vivo settings will establish the feasibility of this flexible implantable system.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.