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

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.