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

 描述（由申请人提供）：了解人类大脑的神经机制和计算原理需要对非人类灵长类动物（NHP）以及小动物进行研究。NHP是最接近人类的物种，可以很容易地进行侵入性研究，并具有高度复杂的感知，运动和认知系统，与我们自己有许多相似之处。然而，NHP大脑的许多最关键的回路无法进行精确的空间和时间观察和操作，因为它们被埋在皮质表面以下超过6 mm，超出了当前成像方式的范围。该项目的目标是探索和优化一种新兴技术（波前整形），该技术将能够使用薄多模光纤在任何深度以最小的组织损伤记录大型神经元群体并调制单独识别的神经元。该方法允许在光纤尖端形成任意三维光图案，并重建流过光纤的高分辨率图像信息。该方法利用了波前整形和多模光纤以及空间调制仪器（数字反射镜设备）的理论理解的最新进展。PI小组的初步结果表明，该技术具有新颖的创新，具有所需的时空带宽来采样大量细胞。然而，这种成像模式仍处于起步阶段，需要在体内应用之前进行调整和优化以用于大脑研究。所提出的方法与现有的笨重的显微内窥镜探头相比具有关键优势，并且可以通过降低多根光纤来轻松扩展以记录多个大脑区域。在这个项目的最后，我们希望能够通过与神经科学实验室的合作，将这项技术付诸实践，从而在清醒的非人类灵长类动物中推动新的发现。

 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.