Many fundamental human behaviors contain multiple sequences performed to reach a desired outcome, such as cooking. Reward is inherently associated with sequence completion and has been shown to generally enhance cognitive control. However, the impact of reward on cognitive sequence processing remains unexplored. To address this key question, we focused on the rostrolateral prefrontal cortex (RLPFC). This area is necessary and exhibits increasing (“ramping”) activation during sequences, a dynamic that may be related to reward processing in other brain regions. To separate these dynamics, we designed a task where reward was only provided after multiple four-item sequences (“iterations”), rather than each individual sequence. Using fMRI in humans, we investigated three possible interactions of reward and sequential control signals in RLPFC: (1) with the visibility of sequential cues, i.e., memory; (2) equally across individual sequence iterations; and (3) differently across individual sequence iterations (e.g., increasing as reward approaches). Evidence from previous, nonsequential cognitive control experiments suggested that reward would uniformly change RLPFC activity across iterations and may depend on the visibility of cues. However, we found the influence of reward on RLPFC ramping increased across sequence iterations and did not interact with memory. These results suggest an active, predictive, and distinctive role for RLPFC in sequence monitoring and integration of reward information, consistent with extant literature demonstrating similar accelerating reward-related dopamine dynamics in regions connected to RLPFC. These results have implications for understanding sequential behavior in daily life, and when they go awry in disorders such as addiction.
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