High-speed Deep Brain Imaging and Modulation with Ultrathin Minimally Invasive Probes

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 DESCRIPTION (provided by applicant): An understanding of the neural mechanisms and computational principles of the human brain requires the study of non-human primates (NHP) in addition to small animals. NHP are the closest species to humans that can be readily studied invasively and have highly sophisticated perceptual, motor, and cognitive systems that share many similarities with our own. However, many of the most critical circuits of the NHP brain are not accessible to precise spatial and temporal observation and manipulation because they are buried more than 6 mm below the cortical surface, beyond the reach of current imaging modalities. The objective of this project is to explore and optimize an emergent technology (wave-front shaping) that will enable recording of large neuron populations and modulation of individually identified neurons, at any depth with minimal tissue damage, using a thin multimode optical fiber. The proposed method allows the formation of arbitrary three-dimensional light patterns at the fiber tip and reconstruction of high-resolution image information flowing across the fiber. The approach utilizes recent advances in theoretical understanding of wavefront shaping and multimode fibers as well as instrumentation for spatial modulation (Digital Mirror Devices). Preliminary results by the PI's group suggest the technique with its novel innovations has the required spatiotemporal bandwidth to sample large numbers of cells. However, this imaging paradigm is still in its infancy and needs to be adapted and optimized for brain studies before it can be applied in-vivo. The proposed approach has key advantages over existing bulky micro-endoscope probes and could be easily scaled up to record from multiple brain regions by lowering multiple fibers. At the end of this project we expect to be in a unique position to transfr the technique into practice through collaborations with neuroscience labs that can drive new discoveries in awake behaving non-human primates.