Biophysical Basis of Functional Connectivity by MRI

描述（由申请人提供）：本提案的总体目标是确定来自大脑的磁共振（MRI）信号静息状态波动的区域间相关性是否可靠地测量区域之间的功能连接。在静息状态下高度相关的低频MRI信号模式的识别可能为描绘和描述神经回路提供了一种强有力的方法。此外，对几种疾病的静息状态连接改变的观察表明，这些相关性反映了大脑组织的一个重要水平。然而，尽管静息状态相关性已经被广泛用于评估大脑功能结构，但它们的精确解释仍不清楚，它们是否是功能连接的直接指标也完全没有得到证实。为了研究连通性，我们将使用高分辨率MRI在高场（9.4T）下描绘麻醉的非人类灵长类动物的皮质网络。猴子脑皮层亚区是一个很好的实验模型，因为该区域的功能和解剖结构已经用侵入性电生理和组织学方法进行了很好的研究。在9.4T时，使用振动触觉刺激的fMRI采集识别出SI皮质内功能不同的皮质区域（3a， 3b和1），每个区域都显示出不同的精细区域内和区域间，以及更远距离的皮质-丘脑连通性。我们将(a)使用刺激驱动的激活图来识别候选区域，然后在亚毫米分辨率下测量猴子大脑的静息状态空间连接模式；(b)测量静息状态BOLD、脑血流量（CBF）和脑血容量（CBV）相关性的本征点扩散函数；(c)确定区域间相关性如何随功能作用、空间分辨率以及BOLD、CBF和CBV信号之间的变化而变化。我们将使用简单的多变量模型将数据简化为可以直接与电生理测量结果进行比较的格式。然后，我们将通过与同一动物的定量电生理和组织学直接比较，验证静息状态MRI信号的连通性测量结果。我们将(a)定量确定电生理学定义的神经元反应图和静息状态fMRI相关图的空间重叠程度；(b)确定来自已识别区域的自发电记录（多单元峰和局部场电位）的哪些特征显示出与BOLD相似的相关模式：(c)通过向经电成像和功能磁共振成像确定的候选区域注射解剖示踪剂，并在死后进行组织学评估，确定通过BOLD和电生理学表现出功能连接的区域是否也表现出很强的区域间解剖连接。我们认为，这些研究对于更好地理解静息状态功能连接测量的神经基础具有重要意义，并将对fMRI在基础和临床神经科学中的应用产生直接影响。

DESCRIPTION (provided by applicant): The overall aim of this proposal is to determine whether inter-regional correlations in resting state fluctuations of magnetic resonance (MRI) signals from the brain reliably measure functional connectivity between regions. The identification of patterns of highly correlated low frequency MRI signals in the resting state potentially provides a powerful approach to delineate and describe neural circuits. Moreover, observations of altered resting state connectivity in several disorders suggest these correlations reflect an important level of brain organization. However, although resting state correlations are already being widely used to assess brain functional architecture, their precise interpretation remains unclear, and whether they are direct indicators of functional connectivity is completely unsubstantiated. To investigate connectivity we will use very high- resolution MRI at high field (9.4T) to delineate cortical networks in anesthetized non-human primates. The sub- regions of SI cortex in monkeys are an excellent experimental model because the functional and anatomical structures of this region have previously been well investigated with invasive electrophysiological and histological methods. At 9.4T, fMRI acquisitions using vibrotactile stimuli identify functionally distinct cortical areas (3a, 3b and 1) within SI cortex, and each displays distinct fine-scale intra- and inter-regional, as well as longer range cortico-thalamic connectivity. We will (a) use stimulus-driven activation maps to identify candidate areas, and then measure resting state spatial connectivity patterns at sub-millimeter resolution in monkey brain; (b) measure the intrinsic point spread function of resting state BOLD, CBF (cerebral blood flow) and CBV (cerebral blood volume) correlations; and (c) determine how inter-regional correlations vary with functional role, spatial resolution and between BOLD, CBF and CBV signals. We will use simple multivariate models to reduce the data to a format by which they can be directly compared to electrophysiological measurements. We will then validate the measurements of connectivity from resting state MRI signals by direct comparisons with quantitative electrophysiology and histology in the same animals. We will (a) determine quantitatively the degree of spatial overlap of electrophysiologically defined neuronal response maps and resting state fMRI correlation maps: (b) determine what features of the spontaneous electrical recordings (multiple-unit spiking and local field potentials) from identified regions shw patterns of correlation similar to BOLD: (c) determine whether areas which appear to be functionally connected by BOLD and electrophysiology also exhibit strong inter-areal anatomical connections by injecting anatomical tracers into candidate regions identified by electrical mapping and fMRI and performing histological assessments post mortem. We believe that the proposed studies have considerable importance for better understanding the neural basis of resting state functional connectivity measures, and will have direct implications and impact on the applications of fMRI in both basic and clinical neuroscience.