Functional Ultrasound Imaging Platform for Brain Research

人类非凡的认知能力是如何在进化史中出现的，这是生物学中最大的问题之一。我们通过研究两个高度智能但远亲相关的动物物种的认知能力及其潜在的神经机制来解决这个问题-猕猴，一种非人类灵长类动物，以及腐肉乌鸦，一种乌鸦，一种乌鸦。通过对特定大脑区域的细致的单单位电生理学和复杂的行为任务，我们发现了一些神经编码原理，这些原理支撑着更高的大脑功能，如数字处理、工作记忆、沟通的意志控制和意识感知。然而，这些功能中的许多并不是孤立于单独的大脑区域，而是依赖于相互连接的大脑区域的大型网络的相互作用。这项应用提出使用一种有前途的创新技术--功能超声成像(FUSI)--来可视化清醒的、行为正常的动物的全脑范围内的神经活动。与更传统的成像技术相比，FUSI提供了一系列吸引人的优势，如大视场、改进的时空分辨率和对动物的最小限制。例如，fMRI很难在行动不便的动物身上进行，而且目前缺乏足够精细的时空分辨率来捕捉大脑深处小核团内的经常性活动。因此，我们求助于FUSI，在那里，当动物处理信息并执行认知要求高的任务时，可以通过神经血管耦合在大脑的大片中测量大脑激活的实时动态。这将让我们史无前例地一瞥各种大脑结构及其相互作用的相对贡献是如何驱动认知的复杂性。除了对大规模网络动力学的洞察之外，这种方法还将有助于指导对有待进一步研究的大脑区域的无偏见选择，进行更多局部的、细粒度的电生理研究。总之，我们乐观地认为，福斯的实验将使我们进入一个新的阶段，探索智能行为的工作原理。

How the extraordinary cognitive abilities of humans emerged through evolutionary history is one of the greatest questions in biology. We approach this question by studying the cognitive capabilities and their underlying neural mechanisms in two highly-intelligent, but distantly-related animal species - macaques, a non-human primate and the carrion crow, a corvid. Through meticulous single-unit electrophysiology of particular brain areas and sophisticated behavioral tasks, we have uncovered some neural coding principles that underlie higher brain functions such as number processing, working memory, volitional control of communication, and conscious perception. However, many of these functions are not isolated to lone brain areas and instead rely on the interaction of large networks of connected brain regions. This application proposes to use a promising, innovative technique - functional ultrasound imaging (fUSI) – to visualize neural activity on a brain-wide scale in awake, behaving animals. fUSi offers an attractive set of advantages compared to more traditional imaging techniques such as a large field of view, improved spatio-temporal resolution, and minimal constraints on the animal. For example, fMRI is difficult to perform in mobile-behaving animals and currently lacks fine enough spatial-temporal resolution to capture recurrent activity within small nuclei deep in the brain. Thus, we turn to fUSi, where it is possible to measure the real-time dynamics of brain activation – via neurovascular coupling – in large slices of the brain while animals process information and perform cognitively-demanding tasks. This will allow us an unprecedented glance at how complex cognitive is driven by the relative contributions of various brain structures and their interactions. Beyond insights into large-scale network dynamics, this approach will also help to guide the unbiased selection of brain areas to be further-studied with more local, fine-grained electrophysiological investigations. Together, we are optimistic that experiments made possible by fUSI will allow us to enter a new phase in our quest to understand the workings of intelligent behavior.