BRAIN CONNECTS: Center for Mesoscale Connectomics

项目总结 了解复杂的神经通路和网络及其产生人类的非凡能力 因此，在活体内准确定位大脑连接点是至关重要的。我们建议在以下方面取得重大进展 通过建立中尺度连接中心(CMC)来绘制这样的大脑图谱。我们将首先绘制中尺度图 额叶和顶叶皮质之间的联系。这些连接可能从属于更高阶的函数 例如注意力、决策、预见和执行控制。一个关键的、未得到重视的特性 皮质连接是其在给定大脑区域内的特定变化，进一步支持了 更精细的连通性描述。不幸的是，传统上，我们在追求上有一个重大差距 创建一个高空间分辨率的人脑“接线图”，特别是自从 人类无法进行中尺度的大脑连通性，也就是解剖学上的轨迹追踪。此外，技术 可以应用于人类的方法，如弥散磁共振成像，可能无法概括解剖结构的连通性 以这样的规模。由于这一差距，我们缺乏准确的人脑接线图，只能 可通过多模式、跨物种、多尺度的办法获得。在这里，我们建议将先进的 解剖束追踪(目标1)、偏振敏感光学相干断层扫描(PS-OCT)(目标2)以及 超高场扩散成像(目标3)，以创建这样的准确的人类和猕猴的接线图 大脑在空间分辨率和物种之间架起了桥梁。 重要的是，我们将通过最先进的注册来计算连接物种、方法和空间尺度 以及纤维取向的联合(多模式)建模。随后，惊人的信息量 每个数据集中的可用数据将使用优化的轨迹照相方法得到进一步增强。 在拟议的资助期结束时，我们预计将有完整的中尺度组织图 额顶连接。我们将准备好将我们的多模式、跨物种的方法应用于整个大脑， 包括大脑皮层和皮质下环路。重要的是，将为计算非侵入性、 在活体中，通过dMRI脑束成像，绘制整个人类大脑的准确中尺度连接图，这将 使研究人员能够将大脑连接与认知、行为和疾病联系起来。

PROJECT SUMMARY To understand complex neural pathways and networks and their remarkable ability to generate human behaviors, it is critical to precisely map brain connectomics in vivo. We propose to make significant advances in such brain mapping by founding the Center for Mesoscale Connectomics (CMC). We will first map the mesoscale connections between the frontal and parietal cortices. These connections likely subserve higher-order functions such as attention, decision-making, prospection, and executive control. One key, underappreciated feature of cortical connectivity is its specific variations within a given brain region, further supporting the critical need for descriptions of connectivity at a finer scale. Unfortunately, there has traditionally been a major gap in our pursuit of creating a human brain “wiring diagram” at high spatial resolution, especially since the gold standard for mesoscale brain connectivity, anatomical tract-tracing, cannot be performed in humans. Moreover, techniques that can be applied to humans, such as diffusion MRI tractography, may not recapitulate anatomical connectivity at this scale. Due to this gap, we are lacking an accurate wiring diagram of the human brain that can only be obtained through a multi-modal, cross-species, multi-scale approach. Here, we propose to combine advanced anatomical tract-tracing (Aim 1), polarization-sensitive optical coherence tomography (PS-OCT) (Aim 2), and ultra-high field diffusion tractography (Aim 3) to create such accurate wiring diagrams of human and macaque brains while bridging spatial resolutions and species. Importantly, we will computationally bridge species, methods, and spatial scales via state-of-the art registration and joint (multimodal) modeling of fiber orientations. Subsequently, the remarkable amount of information available in each dataset will be further enhanced using optimized tractography methods. At the end of the proposed funding period, we expect to have complete maps of the mesoscale organization of fronto-parietal connections. We will be poised to apply our multimodal, cross-species methods brain-wide, including both cortical and subcortical circuits. Importantly, the foundation will be laid for computing noninvasive, in vivo, accurate, mesoscale connectivity maps of whole human brains through dMRI tractography, which will allow researchers to link brain connectivity with cognition, behavior, and disease.