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处理的神经机制。为此，我们记录从恒河猴的视觉皮层使用的内在信号的光学成像和电生理学的组合，而动物从事视觉形式的处理任务。本项目的目标是双重的。我们建议研究一种新的与刺激无关的预期血流动力学信号，我们早些时候在警觉的猕猴V1（初级视觉皮质）中观察到了这种信号。通过这一过程，我们还建议更好地了解神经影像信号，包括功能磁共振成像的生理基础。这个项目源于我们最近的发现，警觉猴V1的血液动力学信号有两个不同的组成部分。一个组成部分是可预测的视觉输入和相关的V1神经元活动。另一个分量-强度相当-是迄今为止未知的血液动力学信号标记任务预期。它反映了一种动脉泵送机制，将新鲜血液输送到大脑皮层，以预测视觉事件。与光学成像同时进行的电极记录表明，这种新的血液动力学信号不是由局部V1神经元活动驱动的，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，预期的刺激无关的血流动力学信号是一种机制的预测唤醒。我们建议测试这一假设的特征的预期和视觉诱发信号，以及它们的相互作用，并询问是否预期信号可以调节视觉诱发的反应和行为。我们发现的新的血液动力学信号也挑战了目前的理解神经影像信号，特别是功能性磁共振成像（fMRI），最常用的工具，人类神经影像。通过这个项目的过程中，我们将探讨在各种视觉感知任务的警觉猕猴的神经影像信号和电生理之间的联系。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对fMRI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，连续双波长固有信号光学成像，结合电极记录，在警觉行为猕猴。对于成像，一个波长在氧合血红蛋白中优先吸收，从而监测血氧;另一个波长在氧合血红蛋白和脱氧血红蛋白中同等吸收，测量血容量。同步电极记录给出了潜在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诱发的反应。这项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。本项目对公共卫生有两个重要影响。我们提出了一种新的脑唤醒机制，从而对注意力或警觉性及其障碍（注意力缺陷障碍等）的过程提供了新的认识。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，这是在临床或科学环境中研究人脑的最常用手段，因此将对正确解释这一至关重要的医学工具产生重大影响。

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.