Investigating the neural representation of structured sequence viewing in the lateral prefrontal cortex of nonhuman primates

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PROJECT SUMMARY The ultimate goal of this research program is to determine the neural mechanisms of sequence monitoring. This knowledge can directly 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. Knowledge of higher-order similarities across sequences (e.g., AAAB, &&&@), abstractions, can aid sequence monitoring. For example, understanding the steps required in each turn in a game, or the repetitive pattern in a poem or song, can improve our awareness and processing. Abstract sequence monitoring includes viewing the sequences that possess abstract structure, active monitoring of this structure, and response. Here, we will determine the neural representation of abstract sequential structure using passive structured sequence viewing. We hypothesize that a key element of sequence structure, position, is encoded in the lateral prefrontal cortex (LPFC) with phasic bursts that in aggregate create population ramping. These neural dynamics can uniquely “tag” each serial position in the sequence, supporting monitoring. This prediction is based on prior literature, and on our discovery that increasing (ramping) blood oxygen level-dependent (BOLD) activity in the rostral LPFC of humans is necessary for sequence execution and underlies sequence monitoring (Desrochers et al., 2015a, 2019). During awake fMRI, we observed parallel BOLD ramping in the LPFC of monkeys performing a structured sequence viewing task. We will use these data to specifically target electrophysiological recordings (Desrochers et al., 2015b; Feingold*, Desrochers* et al. 2012). This viewing task also provides robust BOLD responses to viewed sequence deviants and avoids motor and decision-making confounds while providing experimental flexibility. By using these activity patterns to guide neural recordings, we remove the need for anatomy-based assumptions about cross-species homology and can localize data acquisition with sub-region specificity. We will systematically test the hypotheses that sequence position is characterized by successive phasic increases in neural spiking in LPFC (Aim 1), and that neural activity related to sequence position is modulated by the passage of time and reward expectation (Aim 2). Sequence monitoring is fundamental to many natural behaviors. These data are unique in being guided by, and directly relatable-to, fMRI mapping. While hypothesis- driven, any outcome of these recordings from fMRI-identified brain areas will advance our understanding of this crucial process.