The Neural Basis of Functional MRI Responses

NIMH的壁内研究计划是世界上少数几个可以直接与同时和/或顺序记录的fMRI信号进行比较的地点之一。我们通过与神经生理学成像设备合作，将电生理学和成像技术整合在一起，表现出猴子的警觉。神经生理学成像设备是一个共享的成像设备，致力于非人类灵长类动物的结构和功能脑成像。在之前的工作中，我们已经探索了猴子初级视皮层中神经信号与功能磁共振成像之间的关系。去年，我们发表了一项研究，首次确定了两种信号背离的具体条件。虽然功能磁共振成像和神经信号通常是完全同步的，但我们表明，它们在知觉抑制期间的表现非常不同，在知觉抑制中，刺激被看到但没有被察觉到。这一发现是解释许多人类神经成像研究结果的重要联系，这些研究似乎与电生理记录不一致。 在过去的几个月里，我们发表了一项研究，调查了静息状态fMRI信号的神经基础。这种信号对应于当受试者没有进行任何显性行为时，大脑中发生的自发的内源性fMRI波动，数百个实验室在人脑中进行了广泛的研究。这是非常有趣的，因为在大脑的不同时间点测量的自发波动的统计关系携带着关于大脑功能处理的信息，这种现象被称为功能连接。我们对这种现象的神经基础很感兴趣，因此在清醒的猴子身上同时进行了电生理和功能磁共振测量。令人惊讶的是，我们发现大脑皮层的电活动不仅与特定的功能回路相关，还与大脑皮层大片区域的活动相关。这种近乎全球范围的信号波动是大脑活动的一个重要方面，人类神经成像界忽视了这一点，实际上是把它当作噪音抛弃了。我们的发现表明，这不是噪音，实际上可能代表了大脑功能在代谢消耗中所占比例最高的那一方面。这些发现将影响人类神经成像界考虑和处理在静息状态下测量的全球fMRI信号的方式。 在第二个正在进行的项目中，我们测量了局灶性脑损伤后的fMRI信号。具体地说，我们在非人类灵长类动物的初级视觉皮质(V1)进行了有针对性的消融，然后观察了接受V1输入的区域的fMRI反应在几周后重新出现的程度。我们特别感兴趣的是，fMRI信号的恢复是否表现出与在大脑同一部分测量的单个神经元的反应相同的特性，包括基本恢复时间进程。因此，这种方法需要仔细协调功能磁共振成像、消融和电极植入。然后将这种三管齐下的方法与行为相结合，要求动物告诉我们它们何时检测到视觉目标，以确定神经和fMRI信号如何相互关联，以及它们如何进一步与感知关联。作为这个项目的最后一部分，我们调查了信息可能绕过初级视觉皮质的神经通路。这是通过阻断中间中继核的电活动，然后使用功能磁共振成像来测量反应来实现的。其中一些结果最近发表，其中概述了调节V1非依赖性视觉的重要途径。

The Intramural Reseaerch Program at the NIMH is one of only a handful of sites in the world in which neural activity can be compared directly with simultaneously and/or sequentially recorded fMRI signals. We have integrated electrophysiology and imaging in alert, behaving monkeys by collaborating with the Neurophysiology Imaging Facility, a shared imaging facility dedicated to structural and functional brain imaging in nonhuman primates. In previous work, we have explored the relationship between neural signals and fMRI in the primary visual cortex of monkeys. Last year we published a study that for the first time identified specific conditions under which the two signals diverged. While fMRI and neural signals were normally in perfect sync, we showed that they behaved very differently during perceptual suppression, where a stimulus was seen but not perceived. This finding is an important link toward interpreting the results of many human neuroimaging studies that seem to disagree with electrophysiological recordings. In the last few months, we published a study investigating the neural basis of the resting-state fMRI signal. This signal, corresponding to the spontaneous, endogenous fMRI fluctuations that occur in the brain when a subject is not performing any explicit behavior, is studied widely in the human brain by hundreds of laboratories. It is of great interest because the statistical relationship of spontaneous fluctuations measured at different points in the brain carries information about the brains functional processing, a phenomenon termed functional connectivity. We were interested in the neural underpinnings of this phenomenon, and therefore performed simultaneous electrophysiological and fMRI measurements in awake monkeys. Surprisingly, we found that not only is the electrical activity of the cerebral cortex correlated with specific functional circuits, it is also correlated with activity over large swathes of the cortex. This nearly global span of signal fluctuations is an important aspect of brain activity that has been ignored, literally discarded, by the human neuroimaging community as noise. Our findings suggest that it is not noise, but may, in fact, represent that aspect of brain function that accounts for its highest fraction of metabolic consumption. These findings will influence the manner in which the human neuroimaging community considers and treats the global fMRI signal measured during the resting state. In a second, ongoing project, we have measured fMRI signals following focal brain injury. Specifically, we made targeted ablations in the primary visual cortex (V1) of nonhuman primates, and then observed the extent to which fMRI responses in areas receiving input from V1 reemerged after several weeks. We are particularly interested in whether the recovery of the fMRI signal shows the same properties, including the basic recovery time course, as the responses of single neurons measured in the same part of the brain. This approach therefore requires the careful coordination of fMRI, ablation, and electrode implantation. This three-pronged approach is then combined with behavior, asking the animal to tell us when they detect a visual target, to determine how the neural and fMRI signals related to one another, and how they further relate to perception. As a final portion of this project, we have investigated the neural pathways by which information may bypass the primary visual cortex. This was achieved by blocking electrical activity in an intermediate, relay nucleus, and then using fMRI to measure responses. Some of these results, which outline an important pathway mediating V1-independent vision, were recently published.