Points of contact between neuronal physiology and fMRI

描述（由申请人提供）： 尽管功能性磁共振成像（fMRI）研究已经变得无处不在，并且在临床和基础神经科学中的重要性日益增加，但血氧水平依赖（BOLD）与空间范围和幅度的电生理反应之间的基本关系尚未得到很好的理解。大量粗略尺度（几毫米到厘米）的BOLD研究表明，血流动力学活动的病灶与传统单个单位和病变研究中已知的脑功能的空间定位之间存在合理的相关性。然而，BOLD信号本身并不是神经元活动的直接测量。相反，它是在局灶性神经元活动之后脑氧代谢率（CMR 02）、脑血流量（CBF）和脑血容量（CBV）的变化的复杂卷积。因此，可观察到的BOLD信号的幅度与神经生理学上重要的亚毫米尺度下的潜在神经活动之间的直接和线性相关性因此不能被先验地假设。在本研究中，我们建议以直接的方式解决这些问题。首先，我们建议使用我们实验室最近开发的一种新的“笛卡尔网格”技术，从猫初级视皮层的相同部位进行单/多单元记录和BOLD fMRI。其次，我们将阐明的贡献尖峰和阈下皮层活动在所观察到的BOLD对比仔细映射的经典与经典的感受野边界。第三，已知影响兴奋性和抑制性皮质活动之间平衡的神经活性化合物将在功能性MRI扫描期间局部注入。具体地，将测试GABA和荷包牡丹碱（CABALA拮抗剂）对BOLD信号的幅度、时程和空间延伸的影响。总之，我们相信，我们的项目将提供关键的见解，可观察到的，无处不在的BOLD对比及其潜在的神经生理学起源之间的基本接触点。

DESCRIPTION (provided by applicant): Despite the fact that functional magnetic resonance imaging (fMRI) studies have become ubiquitous and are of ever increasing importance for clinical and basic neurosciences, the fundamental relationships between blood oxygenation level dependent (BOLD) and electrophysiological responses regarding spatial extent and amplitude are not well understood. Numerous BOLD studies at a coarse scale (several millimeter to centimeter) indicated a fair correlation between the foci of hemodynamic activity and the spatial localization of brain functions known from traditional single unit and lesion studies. However, the BOLD signal is not a direct measure of neuronal activity per se. Rather, it is a complex convolution of changes in cerebral metabolic rate of oxygen (CMR02), cerebral blood flow (CBF) and cerebral blood volume (CBV) following focal neuronal activity. Therefore, a direct and linear correlation between the amplitude of the observable BOLD signals and the underlying neural activity at the neurophysiologically important, sub-millimeter scale can therefore not be assumed a priori. In the present study, we suggest to address these questions in a direct manner. First, we propose to perform single/multi unit recording and BOLD fMRI from the same sites of the cat primary visual cortex using a novel "Cartesian grid" technique recently developed in our laboratory. Second, we will elucidate the contribution of spiking and subthreshold cortical activity in the observed BOLD contrast by carefully mapping the extraclassical versus classical receptive field boundaries. Third, neuroactive compounds that are known to influence the balance between excitatory and inhibitory cortical activity will be infused focally during functional MRI scans. In particular, the effect of GABA and bicuculline (CABALA antagonist) on the amplitude, time course, and spatial extend of BOLD signals will be tested. In summary, we believe that our project will provide pivotal insights into the fundamental points of contact between the observable, and ubiquitous BOLD contrast and its underlying neurophysiological origin.