Neurophysiological Basis of Functional MRI Signals

描述(由申请人提供)： 这一建议旨在促进我们对BOLD功能磁共振成像中观察到的血流动力学反应与潜在的神经元活动之间的定量联系的理解。我们假设，大胆的反应反映了神经组织局部区域突触活动的总和。结合功能磁共振成像和活体电生理实验，将在清醒的、行为正常的兔子身上测试这一假设。我们将同样专注于理解BOLD信号的空间和时间域，以及它与单个和多个神经元活动以及局部场电位水平上的电生理活动的关系。BOLD和电生理反应之间的关系将通过两种范式进行研究：单纯使用胡须刺激的简单刺激-反应，以及以胡须刺激为条件刺激的使用痕迹注视条件反射的复杂学习相关范式。在第一个范例中，将使用对特征良好的振动桶系统的刺激来检验反应特性对刺激参数的依赖性，包括幅度、速率和持续时间的变化。我们将使用高空间和时间分辨率的fMRI来研究BOLD功能磁共振成像中有争议的初始“倾角”的空间起源和时间特征。以神经元尖峰电位和局部场电位测量的神经元输入和输出之间的关系，将与在已识别的桶形柱的个别皮质层中以粗略信号演变测量的血流动力学反应进行比较。第二个范式将研究学习的获得和巩固，同时关注海马体感觉皮质和小脑。在学习过程中，这些区域分别作为临时记忆存储场所、永久记忆存储场所和基本基本联想场所。学习过程中小脑皮质和深层核团的反向活动关系将被用来同时检查两个不同区域的激活和去激活。我们对简单的和认知要求很高的范例的比较将验证神经血流动力学依赖是否在不同水平的神经活动中有效，以及BOLD功能磁共振成像是否可能被用作认知功能的非侵入性分析。

DESCRIPTION (provided by applicant): This proposal aims to advance our understanding of the quantitative link between hemodynamic responses observed in BOLD functional MR imaging and the underlying neuronal activities. We hypothesize that the BOLD response reflects the sum of synaptic activity in a local region of neural tissue. Combined fMRI and in vivo electrophysiological experiments will be used in awake, behaving rabbits to test this hypothesis. We will focus equally on understanding both the spatial and temporal domains of the BOLD signal, and its relationship to electrophysiological activity at the level of single- and multi- neuron activity, and of the local field potential. Investigation of the relationship between BOLD and electrophysiological responses will be conducted with two paradigms: simple stimulus-response using whisker stimulation alone, and a complex learning related paradigm using trace eyeballing conditioning with whisker stimulation as the conditioning stimulus. Stimulation of the well-characterized vibrissae barrel system will be used in the first paradigm to examine the dependence of response properties on stimulation parameters including changes in amplitude, rate and duration. The spatial origin and temporal characteristics of the controversial initial "dip" in BOLD fMRI will be investigated using high spatial and temporal resolution fMRI. The relationship between neuronal input and output measured as neuronal spiking and local field potentials will be compared with hemodynamic responses measured as BOLD signal evolution in individual cortical layers of identified barrel columns. The second paradigm will study learning acquisition and consolidation while focusing on the hippocampus, somato sensory cortex and cerebellum. These regions function as the site of temporary memory storage, permanent memory storage, and the basic essential associative site, respectively during the course of learning. The inverse activity relationship of the cerebella cortex and deep nuclei during learning will be used to examine activation and deactivation simultaneously in two different regions. Our comparison of simple and cognitively-demanding paradigms will verify if the neural-hemodynamic dependence is valid across diverse levels of neural activity, and if BOLD fMRI can potentially be used as a noninvasive assay of cognitive functioning.