CRCNS: Real-time neural decoding for calcium imaging

项目主任/首席调查员(最后、第一、中间)：陈荣 项目说明 A.背景和意义 实时神经解码以基于神经活动数据预测行为变量为中心， 其中预测的执行速度可靠地跟上了活动的速度 这一点正在受到监控。神经调节设备正在成为最强大的工具之一 用于治疗脑部疾病，增强神经认知能力，并展示 因果关系(Bergmann等人，2016；Knotkova和Rasche，2015)。一种精确的神经调节 系统(图1)集成了神经活动监控、实时神经解码和 神经调节。在精确的神经调节中，解码设备预测行为变量 基于实时的神经数据流。根据解码结果，神经调节 诸如定时、频率、持续时间和幅度等参数被改变。精确 具有闭环实时反馈的神经调节系统优于固定(开放)神经调节系统 Loop)神经调节范式(Brocker等人，2017；DeBettencourt等人，2015；Ezzyat等人， 2017年)。最近的一项直接脑刺激研究(Ezzyat等人，2017)证明了 精确神经调节相对于开环神经调节的优势。Ezzyat等人。套用 对癫痫患者进行具有解码能力的直接脑刺激，以改善他们的记忆。 他们发现，只有当解码设备提供刺激时，才能增强记忆功能 表示编码效率低，如果在以下情况下提供刺激，则会降低记忆功能 该译码装置具有较高的编码效率。一种开环神经调节系统 使用固定的刺激范式可能并不总是促进记忆功能。 微型细胞成像(Ghosh等人，2011；Kerr和Nimerlijahn，2012；Scott等人，2013) 是研究神经回路最有效的方法之一。它使我们能够研究神经回路 在行为过程中，了解行为、认知和情感的网络架构。 微型细胞成像记录了神经元在细胞和亚秒级空间水平的活动 以及自由活动动物的时间分辨率。微型细胞成像有许多 优势。首先，与活体多电极记录相比，微型钙成像可以 探测视野中的所有细胞，并可视化被监视细胞的空间位置(Kerr等人， 2005)。其次，与磁共振成像相比，磁共振成像测量的是 宏观尺度和低时间分辨率的微型细胞成像提供了高 空间和时间分辨率。第三，纤维光度法(崔等人，2014)缺乏细胞水平 分辨率，而微型细胞成像允许同时跟踪神经钙活动 在细胞空间分辨率下。 同步神经活动 监控和发明 刺激性钙 成象 实时 译码系统 图1精确的神经调节系统。我们的项目 以开发RNDC-Lab为中心。 小灵通398(01/18修订版获批准至2020年3月31日) 第26页 微型细胞成像与真实的- 时间解码功能捕获了 脑科学的中心视觉 大脑倡议，2014)。与 光遗传学，这是一笔巨大的财富 对神经机制的研究 潜在的正常和疾病状态， 并导致精确的神经调节。 然而，开发这样的系统是 这是一项具有挑战性的任务。一个主要的障碍是 关于大图像的分析 生成的流。这个 海量高维数据 生成的流包括 0MB编号0925-0001

Program Director/Principal Investigator (Last, First, Middle): Chen, Rong PROJECT DESCRIPTION A. BACKGROUND AND SIGNIFICANCE Real-time neural decoding centers on predicting behavior variables based on neural activity data, where the prediction is performed at a pace that reliably keeps up with the speed of the activity that is being monitored. Neuromodulation devices are becoming one of the most powerful tools for the treatment of brain disorders, enhancing neurocognitive performance, and demonstrating causality (Bergmann et al., 2016; Knotkova and Rasche, 2015). A precise neuromodulation system (Figure 1) integrates neural activity monitoring, real-time neural decoding, and neuromodulation. In precise neuromodulation, a decoding device predicts a behavior variable based on neural data streams in real-time. Based on the decoding results, neuromodulation parameters such as timing, frequency, duration, and amplitude are changed. Precise neuromodulation systems with closed-loop real-time feedback are superior to the fixed (open- loop) neuromodulation paradigm (Brocker et al., 2017; deBettencourt et al., 2015; Ezzyat et al., 2017). A recent direct brain stimulation study (Ezzyat et al., 2017) demonstrated significant advantages of precise neuromodulation over open-loop neuromodulation. Ezzyat et al. applied direct brain stimulation with decoding capability to patients with epilepsy to improve their memory. They found that stimulation increased memory function only if delivered when the decoding device indicated low encoding efficiency while stimulation decreased memory function if delivered when the decoding device indicated high encoding efficiency. An open-loop neuromodulation system with a fixed stimulation paradigm may not always facilitate memory function. Miniature cellular imaging (Ghosh et al., 2011; Kerr and Nimmerjahn, 2012; Scott et al., 2013) is one of the most powerful ways to study neural circuits. It enables us to investigate neural circuits during behaviors for an understanding of network architecture of behavior, cognition, and emotion. Miniature cellular imaging records neuronal activity at cellular and sub-second levels of spatial and temporal resolution in freely moving animals. Miniature cellular imaging has many advantages. First, compared with in vivo multi-electrode recording, miniature calcium imaging can probe all cells in the field of view, and visualize the spatial location of monitored cells (Kerr et al., 2005). Second, compared with magnetic resonance imaging, which measures brain activity at the macroscopic scale and with low temporal resolution, miniature cellular imaging provides high spatial and temporal resolution. Third, fiber photometry (Cui et al., 2014) lacks cellular-level resolution, while miniature cellular imaging allows concurrent tracking of neural calcium activities at cellular spatial resolution. Simultaneous neural activity monitoring and intetvention Stimulation Calcium imaging Real-time decoding system Figure 1 A precise neuromodulation system. Our project centers on developing RNDC-Lab. PHS 398 (Rev. 01 /18 Approved Through 03/31/2020) Page 26 Miniature cellular imaging with real- time decoding capability captures the central vision of brain science, (The brain initiative, 2014). Combined with optogenetics, it is a tremendous asset to studying neural mechanisms underlying normal and disease states, and leads to precise neuromodulation. However, developing such systems is a challenging task. A major obstacle is the analysis of the large imaging streams that are generated. The massive high-dimensional data streams that are generated include 0MB No. 0925-0001