Lesions of Ventrolateral Prefrontal or Anterior Orbitofrontal Cortex in Primates Heighten Negative Emotion

Background: Heightened fear and anxiety are core symptoms of a variety of neuropsychiatric disorders. They are associated with structural and activity changes throughout neural circuitry that includes the ventral and medial prefrontal cortices (PFC), the amygdala, and hippocampus. Although the contributions of the medial PFC, amygdala, and hippocampus to fear and anxiety have been studied extensively with animal models, the selective roles of the ventral PFC-including the ventrolateral prefrontal cortex (vlPFC) and orbitofrontal cortex-are poorly understood. Methods: We investigated the effects of selective excitotoxic lesions of either the vlPFC or anterior orbitofrontal cortex (antOFC) on anxious behavior and Pavlovian conditioned autonomic and behavioral fear responses in the New World primate, the common marmoset. Results: Both vlPFC and antOFC lesions resulted in stronger, less adaptable conditioned fear responses. They also heightened the anxiety responses of a marmoset to a human intruder. In contrast, only a lesion of the vlPFC affected the coping style that a marmoset displayed in the presence of the human intruder, increasing the likelihood of proactive mobbing. Conclusions: These results suggest that both the antOFC and vlPFC can downregulate fear and anxiety and, together, provide necessary but independent contributions to the top-down control of negative emotion.