Neural Responses in Dorsal Prefrontal Cortex Reflect Proactive Interference during an Auditory Reversal Task

Task-related plasticity in the brain is triggered by changes in the behavioral meaning of sounds. We investigated plasticity in ferret dorsolateral frontal cortex (dlFC) during an auditory reversal task to study the neural correlates of proactive interference, i.e., perseveration of previously learned behavioral meanings that are no longer task-appropriate. Although the animals learned the task, target recognition decreased after reversals, indicating proactive interference. Frontal cortex responsiveness was consistent with previous findings that dlFC encodes the behavioral meaning of sounds. However, the neural responses observed here were more complex. For example, target responses were strongly enhanced, while responses to non-target tones and noises were weakly enhanced and strongly suppressed, respectively. Moreover, dlFC responsiveness reflected the proactive interference observed in behavior: target responses decreased after reversals, most significantly during incorrect behavioral responses. These findings suggest that the weak representation of behavioral meaning in dlFC may be a neural correlate of proactive interference.\n\nSignificance StatementNeural activity in prefrontal cortex (PFC) is believed to enable cognitive flexibility during sensory-guided behavior. Since PFC encodes the behavioral meaning of sensory events, we hypothesized that weak representation of behavioral meaning in PFC may limit cognitive flexibility. To test this hypothesis, we recorded neural activity in ferret PFC, while ferrets performed an auditory reversal task in which the behavioral meanings of sounds were reversed during experiments. The reversal task enabled us study PFC responses during proactive interference, i.e. perseveration of previously learned behavioral meanings that are no longer task-appropriate. We found that task performance errors increased after reversals while PFC representation of behavioral meaning diminished. Our findings suggest that proactive interference may occur when PFC forms weak sensory-cognitive associations.