CAREER: Testing the neural representation of sequences in nonhuman primate frontal cortex using fMRI-localized electrophysiology

人类和动物都擅长跟踪对生存至关重要的模式，并使用这些信息来预测和做出正确的反应。例如，当我们坐在公交车上时，我们会跟踪车站的顺序，这样我们就可以在正确的时间准备好、站起来和离开。为了做出这些反应，我们必须跟踪个别事件的顺序。除了跟踪序列，我们的生活还取决于我们生成序列的能力，这是从系鞋带到形成句子或写交响乐等一切事情的基础。理解和遵循序列也是我们学习能力的基础。损害这种追踪的疾病或伤害可能会对正常生活产生毁灭性的影响。然而，尽管跟踪序列很重要，但我们的大脑如何支持这一能力几乎是未知的。即使是最先进的人工智能系统也无法解决许多人类和动物可以轻松完成的顺序问题。除了科学研究促进对序列的神经基础的理解，这个项目还包括一个广泛的多管齐下的推广工作：与社区、学校和以研究为主题的博览会上的教育活动分享神经科学最新发现的兴奋，向不同背景的学生教授神经科学，以及举办一个年度会议，重点是鼓励和支持希望在STEM领域从事职业的女性。为了加深我们对序列表示的理解，研究人员将记录模式生物(猕猴)在执行听觉和视觉序列跟踪任务时的大脑活动。这项任务将阐明大脑跟踪顺序信息的两种方式。例如，如果一个序列是“abcd”，知道“B”之后是什么的一种方法就是知道“C”总是在“B”之后。这将是一种关系表示。知道下一步是什么的另一种方法是，“C”始终是序列中的第三项--一个序数表示法。我们假设大脑的不同区域跟踪这两种不同类型的序列信息：前额叶皮质(MPFC)的内侧部分跟踪顺序位置-哪个项目与序列中的哪个位置(C是第三)相匹配，而前额叶皮质(LPFC)的外侧部分从MPFC接收顺序信息，以跟踪哪个项目与哪个地方(C是第三)相关联，并将其与关于下一个项目(C在B之后)的关系信息相结合。研究人员将以两种不同的方式记录猴子执行任务时的大脑活动：通过记录PFC和其他脑区的单个细胞的活动，以及通过全脑神经成像(使用功能磁共振成像-fMRI)。使用这两种互补的方法可以提供两种独立的证据，它们可以结合在一起，以更深入地了解序列表示。这些实验有望加深对大脑如何跟踪序列以及大脑如何学习和执行复杂任务的理解，这些任务需要一系列连续的动作。对非人类灵长类动物的序列跟踪任务和序列表示的研究将阐明并洞察人类认知和人类在类似测序任务中表现的神经基础。该项目由认知神经科学计划和既定的激励竞争研究计划(EPSCoR)联合资助。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Humans and animals are great at keeping track of patterns that are important for survival and using this information to predict and respond the right way. For example, when sitting on a bus, we track the order of stops, so we can get ready, stand-up and exit at the right time. To make these responses, we must keep track of the order of individual events. In addition to tracking sequences, our lives are also shaped by our abilities to generate sequences, which are foundational for everything from tying shoelaces to forming a sentence or writing a symphony. Understanding and following sequences also underlies our ability to learn. Illnesses or injuries that impair this tracking can have devastating effects on normal life. However, despite the fundamental importance of tracking sequences, how our brain supports this ability is mostly unknown. Even the most advanced artificial intelligence systems cannot solve many sequential problems that humans and animals can easily perform. In addition to scientific research advancing understanding of the neural basis of sequences, this project also includes an extensive multipronged outreach effort: sharing the excitement of recent discoveries in neuroscience with educational events in the community, in schools and during research-themed fairs, teaching neuroscience to students with diverse backgrounds, and running an annual conference focused on encouraging and supporting women who wish to pursue a career in STEM fields.To deepen our understanding of sequence representation, researchers will record brain activity from a model organism (macaque monkeys) during performance of auditory and visual sequence tracking tasks. This task will illuminate two ways the brain could track sequential information. For example, if a sequence is “ABCD”, one way to know what comes after “B” is to learn that “C” always comes after “B”. This would be a relational representation. Another way to know what comes next is that “C” is always the third item in the sequence – an ordinal representation. We hypothesize that different areas of the brain track these two different kinds of sequence information: the medial part of prefrontal cortex (MPFC) tracks ordinal position - which item goes with which place in the sequence (C is third), and the lateral part of prefrontal cortex (LPFC) receives ordinal information from MPFC to track which item goes with which place (C is third) and combines this with relational information about which item comes next (C after B). Researchers will record brain activity in two different ways while monkeys perform the task: by recording the activity of single cells in the PFC and other brain areas, and by whole brain neuroimaging (using functional magnetic resonance imaging - fMRI). Using these two complementary methods provides two independent kinds of evidence which can be integrated to give more insight into sequence representation. These experiments hold the promise of leading to a deeper understanding of how the brain tracks sequences and how the brain learns and performs complex tasks, which require a sequence of successive actions. The studies on sequence tracking tasks and sequence representation in non-human primates will illuminate and give insight into human cognition and the neural basis of human performance on similar sequencing tasks.This project is jointly funded by the Cognitive Neuroscience Program and by the Established Program to Stimulate Competitive Research (EPSCoR).This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.