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

 描述(申请人提供)：要了解人脑的神经机制和计算原理，除了研究小动物外，还需要研究非人类灵长类动物(NHP)。NHP是最接近人类的物种，可以很容易地进行侵入性研究，并且拥有高度复杂的感知、运动和认知系统，与我们自己的有许多相似之处。然而，NHP大脑中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下6 mm以上，超出了目前的成像模式的范围。该项目的目标是探索和优化一种新兴技术(波前整形)，该技术将能够使用细长的多模光纤在任何深度记录大量神经元并调制单独识别的神经元，同时将组织损伤降至最低。提出的方法允许在光纤尖端形成任意的三维光图案，并重建流经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理论方面的最新进展，以及用于空间调制的仪器(数字镜子设备)。PI小组的初步结果表明，这项具有创新精神的技术具有所需的时空带宽，可以对大量细胞进行采样。然而，这一成像范式仍处于初级阶段，需要适应和优化大脑研究，然后才能在体内应用。与现有笨重的显微内窥镜探头相比，该方法具有关键优势，通过降低多个纤维，可以很容易地扩大到从多个大脑区域进行记录。在这个项目结束时，我们希望通过与神经科学实验室的合作，将这项技术转化为实践，从而推动在清醒状态下表现出非人类行为的灵长类动物方面的新发现。

 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.