Close-Loop Deep Brain Optoacoustic Stimulation at Sub-millimeter Precision

Neuromodulation has been an invaluable approach for basic studies of neural circuits and for effective clinical treatment of neurological diseases. Electrical stimulation is widely used and forms the basis of current implantable devices. For example, the applications of electrical stimulation based deep brain stimulation (DBS) has been applied to epilepsy, Parkinson’s disease and depression, and is rapidly expanding, with more than 350 trials and 62% them for movement disorders1. Yet, the limited spatial precision due to current spread, fMRI incompatibility due to metal and electronic components, and interference with the electrical recording required for the closed loop control limit the further improvement of the existing electrical implants, such as DBS. These limitations highlight an unmet need for new non-genetic, highly precise, fMRI compatible, and translatable neural stimulation technologies. Here we propose a non-genetic deep brain optoacoustic neural stimulation (DBOAS) technology through a multiple functional fiber based optoacoustic emitter (mFOE). We integrate conducting electrodes and optoacoustic emitters converted from polymer optical fibers into a miniaturized multifunctional fiber. Such mFOE enables a sub-100-micron stimulation at the each site for volumetric stimulation by selective light guiding. It provides closed loop control without electrical interference. We will design the volumetric mFOE, validate our hypothesis through a system design for DBOAS, and evaluate treatment effect of the closed-loop DBOAS in a mouse epilepsy model. A multi-disciplinary team with complementary expertise is assembled to perform the proposed activities. Prof. Chen Yang (PI) is an expert in nanomaterials and nanomaterial-based devices for neuromodulation. Prof. Xiaoting Jia (co-I) is an expert in polymer fiber devices for optogenetic brain modulation and electrical recording. Prof. Ji-Xin Cheng (collaborator) is an expert in optics and photoacoustic devices. Dr. Jeffery Schweitzer (collaborator, MGH) is a neurosurgeon and an expert in implantable treatments for neurological disorders, such as epilepsy. We focus on closed loop DBOAS in this project, and its potential applications in other clinical conditions and fundamental studies are broad, including treating neurological diseases in brain, coded retinal stimulation and brain-machine interface.