Biophysical Basis of Functional Connectivity by MRI

描述(申请人提供)：这项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衡量区域之间的功能连接。识别静息状态下高度相关的低频MRI信号的模式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性改变的观察表明，这些相关性反映了大脑组织的重要水平。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，但它们的准确解释仍然不清楚，它们是否是功能连接的直接指标也完全没有证据。为了研究连通性，我们将使用非常高分辨率的高场磁共振成像(9.4T)来描绘麻醉的非人类灵长类动物的皮质网络。猴SI皮质的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被有创性的电生理和组织学方法研究得很好了。在9.4T，使用振动触觉刺激的fMRI采集识别SI皮质内的功能不同的皮质区域(3a、3b和1)，每个区域都显示不同的精细尺度的区域内和区域间以及更远距离的皮质-丘脑连接。我们将(A)使用刺激驱动的激活图来识别候选区域，然后测量猴子大脑亚毫米分辨率的静息状态空间连接模式；(B)测量静息状态BOLD、CBF(脑血流量)和CBV(脑血流量)的内在点扩散函数；以及(C)确定区域间的相关性如何随功能角色、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减少到一种格式，通过这种格式，它们可以直接与电生理测量进行比较。然后，我们将通过与同一动物的定量电生理学和组织学直接比较，验证来自静止状态MRI信号的连通性测量结果。我们将(A)定量确定电生理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)确定识别区域的自发电记录(多单位峰电位和局部场电位)的哪些特征表现出类似BOLD的关联模式：(C)通过向通过电映射和fMRI确定的候选区域注射解剖示踪剂并进行尸检后组织学评估，确定似乎通过BOLD和电生理学在功能上相连的区域是否也显示出强大的区域间解剖联系。我们认为，这些研究对于更好地理解静息状态功能连通性测量的神经基础具有相当重要的意义，并将对fMRI在基础和临床神经科学中的应用产生直接的影响和影响。 与公共健康相关：当受试者处于休息状态，并且没有从事任何特定的精神活动或任务时，对几分钟内获得的一系列脑部磁共振图像的分析表明，基线具有很强的区域间相关性 核磁共振信号似乎反映了可识别的神经回路。利用这种功能连通性有相当大的潜力，但到目前为止还没有研究证实这些信号变异揭示了神经电活动的实际解剖连通性或相关变异。拟议的研究将通过观察非人类灵长类动物大脑中非常高的分辨率来建立这些联系。

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. PUBLIC HEALTH RELEVANCE: The analysis of series of magnetic resonance images of the brain acquired over a period of minutes while the subject is in a resting state, and not engaged in any specific mental activity or task, reveals strong inter-regional correlations of the baseline MRI signal that appear to reflect identifiable neural circuits. There is considerable potential in exploiting this functional connectivity, but thus far there have been no studies to validate that these signal variations reveal actual anatomic connectivity or correlated variations in neural electrical activity. The studies proposed would establish these links by looking at very high resolution in the brains of non-human primates.