CRCNS US-Israel Research Proposal: Multiscale analysis of brain-wide neuromodulation

动机、情绪和警觉性的持续变化在健康的大脑功能中起着重要作用，在神经和精神疾病中被破坏。该项目将分析支撑这些行为状态变化的神经回路。它将通过开发一种新的计算分析方法，在斑马鱼大脑活动的记录上验证这种方法，并使用这种方法来分析人类的大脑活动。该项目还将开发一个从大神经数据中提取知识的在线教育研讨会。研讨会将提供一种动手的方法来分析和建模大型神经科学数据集——从模拟到斑马鱼再到人类——以这种方式将有助于培养新一代的计算神经科学家。该项目提出了一个新的计算框架，用于跨物种和尺度的功能成像数据中神经调节的统计推断。它将分三步验证和部署这个框架。首先，它将在具有已知基础真理的神经网络活动模拟中验证该框架。其次，它将把这个框架部署到斑马鱼全脑细胞分辨率钙成像数据。这一部署将使神经调节系统的发现成为可能，并将这些发现与现有的解剖学知识进行对比。第三，它将把这个框架转化为人类功能MRI数据的分析。这种翻译将有助于非侵入性地推断人类大脑状态下的神经调节。总的来说，这些步骤的完成将提供一个综合的统计框架，用于推断跨物种和空间尺度的全脑神经调节系统。在短期内，这项研究的完成将为研究人员提供从非侵入性成像中推断神经调节作用的新方法。从长远来看，这项研究的完成将有助于检测不同大脑状态下的神经调节失调。总的来说，这些成果将加速发现大脑活动和功能的基础方面。该项目由生物科学理事会的神经系统集群和计算机与信息科学与工程理事会的信息和智能系统部门联合资助。美国-以色列两国科学基金会（BSF）正在资助一个伙伴项目。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Ongoing changes in motivation, mood, and alertness, play an important role in healthy brain function, and are disrupted in neurological and psychiatric disorders. The project will analyze neural circuitry that underpins these changes across behavioral states. It will do so by developing a new computational analysis method, validating this method on recordings of zebrafish brain activity, and using this method to analyze human brain activity. The project will also develop an online educational workshop on extraction of knowledge from big neural data. The workshop will provide a hands-on approach to analysis and modeling of large neuroscience datasets — from simulations to zebrafish to humans — and in this way will help train a new generation of computational neuroscientists.The project proposes a new computational framework for statistical inference of neuromodulation in functional imaging data across species and scales. It will validate and deploy this framework in three steps. First, it will validate this framework in simulations of neuronal network activity with known ground truth. Second, it will deploy this framework to zebrafish brain-wide cell-resolution calcium imaging data. This deployment will enable the discovery of neuromodulatory systems, and the benchmarking of these discoveries against existing anatomical knowledge. Third, it will translate this framework to analysis of human functional MRI data. This translation will facilitate noninvasive inference of neuromodulation in living humans across brain states. Collectively, completion of these steps will deliver an integrative statistical framework for inferring brain-wide neuromodulatory systems across species and spatial scales. In the short term, this completion will provide investigators with new ways to infer effects of neuromodulation from non-invasive imaging. In the long term, this completion will help facilitate detection of dysregulated neuromodulation across brain states. Collectively, these deliverables will accelerate discovery of foundational aspects of brain activity and function.This project is funded jointly by the Neural Systems Cluster in the Biological Sciences Directorate and the Division of Information and Intelligent Systems in the Computer and information Science and Engineering Directorate. A companion project is being funded by the US-Israel Binational Science Foundation (BSF).This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.