Anticipatory Hemodynamic Signals in Primary Visual Cortex

描述（由申请人提供）：我们的长期目标是了解皮层通路早期视觉加工的神经机制。为此，我们利用内在信号光学成像和电生理学相结合的方法记录了恒河猴在进行视觉形式处理任务时的视觉皮层。当前项目的目标是双重的。我们建议研究一种新的不依赖刺激的预期血流动力学信号，我们早些时候在警觉猕猴V1（初级视觉皮层）中观察到。通过这一过程，我们也提出了更好地理解包括fMRI在内的神经成像信号的生理基础。这个项目源于我们最近的发现，即警觉猴V1的血流动力学信号有两个不同的组成部分。一种成分是通过视觉输入和相关的V1神经元活动来预测的。另一个成分-强度相当-是迄今未知的血流动力学信号，标志着任务预期。它反映了一种动脉泵送机制，在预期的视觉事件中将新鲜血液输送到皮层。与光学成像同时进行的电极记录显示，这种新的血流动力学信号不是由局部V1神经元活动驱动的，这与从相同记录部位获得的视觉诱发反应形成鲜明对比。我们假设不依赖于预期刺激的血流动力学信号是一种预测性唤醒机制。我们建议通过描述预期信号和视觉诱发信号的特征，以及它们之间的相互作用来验证这一假设，并询问预期信号是否可以调节视觉诱发反应和行为。我们对新的血流动力学信号的发现也挑战了目前对神经成像信号的理解，特别是功能磁共振成像（fMRI），这是人类神经成像最常用的工具。通过本项目，我们将研究警觉猕猴在各种视觉感知任务中的神经成像信号与电生理之间的联系。这将是一个无与伦比的机会，可以在最接近人类的动物模型中获得功能磁共振成像的新见解。我们的新发现是由于我们实验室开发的一种新的成像技术，连续双波长本态信号光学成像，结合电极记录，在警觉行为的猕猴中获得的。成像时，一个波长优先被氧合血红蛋白吸收，从而监测血液氧合；另一种波长，在含氧和脱氧血红蛋白中被同等吸收，用来测量血容量。同时的电极记录给出了潜在的神经元活动的电生理测量。连续的记录使我们能够区分正在进行的信号和刺激引起的反应。该技术将构成当前项目的基础，提供一个独特的工具组合来回答手头的问题。该项目对公共卫生有两个重要影响。我们建议描述一种新的大脑觉醒机制，从而为注意力或警觉性过程及其障碍（注意缺陷障碍等）提供新的视角。此外，我们的工作挑战了目前对功能性磁共振成像（fMRI）的理解，fMRI是临床或科学环境中研究人脑最常用的手段，因此将对这一至关重要的医疗工具的正确解释产生重大影响。

Description (provided by applicant): Our long-term goal is to understand the neural mechanisms of visual processing early in the cortical pathway. To this end we record from rhesus macaque visual cortex using a combination of intrinsic-signal optical imaging and electrophysiology while the animals are engaged in visual form processing tasks. The goal of the current project is two-fold. We propose to study a novel stimulus-independent anticipatory haemodynamic signal that we observed earlier in alert macaque V1 (primary visual cortex). Through this process we also propose to better understand the physiological basis of neuroimaging signals including fMRI. This project derives from our recent discovery that haemodynamic signals in alert monkey V1 have two distinct components. One component is predictable by visual input and associated V1 neuronal activity. The other component - of comparable strength - is a hitherto unknown haemodynamic signal marking task anticipation. It reflects an arterial pumping mechanism bringing fresh blood to cortex in anticipation of predicted visual events. Electrode recordings conducted simultaneously with the optical imaging showed that this novel haemodynamic signal is not driven by local V1 neuronal activity, in dramatic contrast to visually evoked responses obtained from the same recording sites. We hypothesize that the anticipatory stimulus-independent haemodynamic signal is a mechanism of predictive arousal. We propose to test this hypothesis by characterizing the anticipatory and visually evoked signals, and their interaction, and asking if the anticipatory signal can modulate visually evoked responses and behavior. Our finding of the novel haemodynamic signal also challenges current understandings of neuroimaging signals, notably functional magnetic resonance imaging (fMRI), the most commonly used tool for human neuroimaging. Through the course of this project we will investigate the links between neuroimaging signals and electrophysiology in the alert macaque in a variety of visual perceptual tasks. This will be an unparalleled opportunity to gain new insights into fMRI in an animal model that is the closest possible to the human. Our novel findings were obtained as a result of a new imaging technique developed in our laboratory, continuous dual-wavelength intrinsic-signal optical imaging, combined with electrode recordings, in alert behaving macaques. For the imaging, one wavelength is absorbed preferentially in oxygenated haemoglobin, thus monitoring blood oxygenation; the other wavelength, absorbed equally in oxygenated and deoxygenated haemoglobin, measures blood volume. The simultaneous electrode recordings give an electrophysiological measure of the underlying neuronal activity. The continuous recording allows us to distinguish between ongoing signals and stimulus-evoked responses. This technique will form the basis of the current project, giving a unique combination of tools to answer the questions at hand. PUBLIC HEALTH RELEVANCE This project has two significant implications for public health. We propose to characterize a novel mechanism of brain arousal, thus shedding new light on processes of attention or alertness and their disorders (attention deficit disorder etc.). Further, our work challenges the current understanding of functional magnetic resonance imaging (fMRI), the most commonly used means of studying the human brain in clinical or scientific settings, and will therefore have major implications for the correct interpretation of this critically important medical tool.