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。我们通过研究两种高度智能但亲缘关系较远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）和食腐乌鸦（一种鸦）。通过对特定大脑区域和复杂的行为任务进行细致的单单元电生理学研究，我们发现了一些神经编码原理，这些原理是数字处理、工作记忆、交流的意志控制和意识感知等高级大脑功能的基础。然而，许多这些功能并不是孤立于单独的大脑区域，而是依赖于连接的大脑区域的大网络的相互作用。这个应用程序建议使用一种很有前途的创新技术——功能性超声成像（fUSI）——在清醒的、有行为的动物的全脑范围内可视化神经活动。与更传统的成像技术相比，fUSi提供了一系列吸引人的优势，如大视野，提高时空分辨率，对动物的限制最小。例如，功能磁共振成像很难在活动行为的动物身上进行，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内的周期性活动。因此，我们转向fUSi，在那里可以测量大脑激活的实时动态-通过神经血管耦合-在动物处理信息和执行认知要求的任务时，在大脑的大切片中。这将使我们前所未有地了解复杂的认知是如何由各种大脑结构及其相互作用的相对贡献所驱动的。除了对大规模网络动力学的见解之外，这种方法还将有助于指导对大脑区域的公正选择，以便通过更局部、更细粒度的电生理调查进行进一步研究。总之，我们乐观地认为，fUSI所做的实验将使我们在探索理解智能行为的运作过程中进入一个新的阶段。

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.