MICROSCOPIC FOUNDATION OF MULTIMODAL HUMAN IMAGING

人脑的计算特性源于数十亿神经元之间错综复杂的相互作用 连接在复杂的网络中。然而，我们在健康人脑中研究这些网络的能力有限 使用非侵入性技术的必要性。这与动物模型形成对比，在动物模型中， 由于显微光学技术的最新进展， 成像和遗传学。因此，神经科学今天面临的一个核心挑战是利用这些机制， 从动物研究中获得的见解，以准确地从人类非侵入性信号中得出生理推断。 在拟议的项目中，我们专注于“校准”血氧水平依赖（BOLD）功能磁共振成像 这项技术提出了这样的问题：“潜在神经元活动的哪些方面可以可靠地推断出来， 从非侵入性脑血流量（CBF）和脑氧代谢率（CMRO 2）的观测？”和 “将校准的BOLD与脑磁图相结合可以获得哪些进一步的信息 (MEG)?" 我们的中心假设是，特定的神经元细胞类型在它们驱动的方式中具有可识别的“签名”。 能量代谢（CMRO2）、血流量（CBF）的变化，并有助于宏观电信号 (MEG电流偶极动力学）。因为其他因素可能会影响基线流量和代谢，我们的重点是 诱发的绝对CMRO2和CBF变化与增加或减少的神经元活动。 我们将在小鼠和人类中进行平行实验，以经验性地将这些点连接起来。 脑功能组织的微观特性及其在宏观层次上的表现 非侵入性的可观测性基于实验结果，我们将开发一个计算框架 这将在尺度和测量模式之间建立联系， 神经元回路活动的关键方面，从非侵入性测量在人类。 拟议的项目将提供一个定量探针，用于人类大脑中已知细胞类型的神经元活动 使人类fMRI研究的范式转变：从简单的fMRI信号变化映射到明确的 估计特定神经元细胞类型的相应活性水平，而不产生 血流和代谢的基线状态。

The computational properties of the human brain arise from an intricate interplay between billions of neurons connected in complex networks. However, our ability to study these networks in healthy human brain is limited by the necessity to use noninvasive technologies. This is in contrast to animal models where a rich, detailed view on the cellular level brain function has become available due to recent advances in microscopic optical imaging and genetics. Thus, a central challenge facing neuroscience today is leveraging these mechanistic insights from animal studies to accurately draw physiological inferences from human noninvasive signals. In the proposed project, we focus on the “Calibrated” Blood Oxygenation Level Dependent (BOLD) fMRI technology asking the questions: “Which aspects of the underlying neuronal activity can be reliably inferred from noninvasive cerebral blood flow (CBF) and Cerebral Metabolic Rate of O2 (CMRO2) observables?” and “What further information can be obtained from combining Calibrated BOLD with Magnetoencephalography (MEG)?” Our central hypothesis is that specific neuronal cell types have identifiable “signatures” in the way they drive changes in energy metabolism (CMRO2), blood flow (CBF) and contribute to macroscopic electrical signals (MEG current dipole dynamics). Because other factors may affect baseline flow and metabolism, our focus is on the evoked absolute CMRO2 and CBF changes associated with increased or decreased neuronal activity. We will perform parallel experiments in mice and humans to empirically connect the dots between the microscopic properties of brain's functional organization and their manifestation on the macroscopic level of noninvasive observables. Based on the experimental results, we will then develop a computational framework that will establish connections between scales and measurement modalities enabling robust estimation of the critical aspects of neuronal circuit activity from noninvasive measurements in humans. The proposed project will deliver a quantitative probe for neuronal activity of known cell types in human brain enabling a paradigm shift in human fMRI studies: from a simple mapping of fMRI signal change to the explicit estimation of the respective activity levels of specific neuronal cell types without confounding effects of the baseline state of flow and metabolism.