PROJECT SUMMARY
The ultimate goal of this research program is to determine the neural mechanisms of sequence monitoring across
species. This knowledge can contribute to understanding new treatments for disorders where sequential
behaviors are disrupted, such as obsessive-compulsive disorder (OCD). Daily, we monitor sequences of visual
information such as the series of bus or train stops when looking for the correct exit. Sequence monitoring is the
active process of tracking the order of subsequent “states” or steps. Monitoring is distinct from other well-studied
sequence processes, such as explicit memorization, or potentially more automatic behaviors such as a series of
motor outputs (e.g., playing the piano) or statistical sequence learning. However, the monitoring aspects of
sequence processing remain largely unknown.
The goal of this proposal is to determine the neural mechanisms of nonmotor and nonspatial sequence
monitoring across species. Reflecting its importance, a large network of cortical and subcortical areas is
implicated in sequence processing, including frontal cortices, premotor cortex, medial temporal lobe, basal
ganglia, hippocampus, and cerebellum. When focusing on high-level monitoring of nonmotor and nonspatial
sequences by human and nonhuman primates, our Preliminary Data and other evidence indicates that lateral
and medial prefrontal cortices (LPFC and MPFC, respectively), play a unique role. However, the specific
contributions of each have not been determined. Two key features of sequences (e.g., ABCD) that may be
encoded in neural activity are their ordinality or item-in-position associations (C in position 3) and temporal
context or item-item associations (B is after A). Behavioral studies indicate that both kinds of information are
used to monitor sequences. Previous studies, including our own, have found ordinality encoding in LPFC and
MPFC. However, prior work has not established whether temporal encoding may additionally exist in these
regions and any coding differences between these areas. We hypothesize MPFC primarily codes ordinality, and
LPFC uses signals from MPFC to code ordinality and temporal context.
We will directly test these hypotheses by triangulating behavioral, whole brain, and cellular data in studies across
species. We will apply the unique capabilities of our lab to study cognitive capabilities across brain areas in
behaving monkeys using fMRI (Aim 1), the functional homology and correspondence to more abstract sequential
tasks in humans using fMRI (Aim 2), and use these signals to guide electrophysiology in monkeys (Aim 3).
Parallel fMRI studies across species will allow us to leverage each for distinct strengths in hypothesis testing:
detailed neurophysiology in monkeys, and detailed cognitive studies in humans.
