Abstract

The ventral prefrontal cortex is an integral part of the neural circuitry that is dysregulated in mood and anxiety disorders. However, the contribution of its distinct sub-regions to the regulation of negative emotion are poorly understood. Recently we implicated both the ventrolateral prefrontal cortex (vlPFC) and anterior orbitofrontal cortex (antOFC) in the regulation of conditioned fear and anxiety responses to a social stimulus, i.e., human intruder, in the marmoset monkey. In the present study we extend our investigations to determine the role of these two regions in regulating innate responses and coping strategies to a predator stimulus, i.e., a model snake. Both the vlPFC and antOFC lesioned groups exhibited enhanced anxiety-related responses to the snake in comparison to controls. Both groups also showed a reduction in active coping behavior. These results indicate that the vlPFC and antOFC contribute independently to the regulation of both innate fear and, as previously reported, conditioned fear, and highlight the importance of these regions in producing stimulus-appropriate coping responses. The finding that dysregulation in two distinct prefrontal regions produces the apparently similar behavioral phenotype of heightened negative emotion provides insight into the varied etiology that may underlie this symptom across a wide variety of neuropsychiatric conditions with implications for personalized treatment strategies.

Highlights

  • Ever since the 19th century case report of Phineas Gage, whose emotional character dramatically changed after considerable damage to his ventromedial prefrontal cortex, the PFC has been the focus of investigation for the regulation of emotions

  • Hypoactivation across the ventrolateral PFC and orbitofrontal cortex (OFC) have been reported across different types of anxiety disorders (Etkin et al, 2007; Milad and Rauch, 2007; Killgore et al, 2013). These studies demonstrate significant association between prefrontal neural activities and pathological anxiety, in order to understand the etiology of these disorders, it is essential to establish the causal role of the prefrontal cortex in emotion regulation

  • This suggests that the novel white box may have induced a mild state of anxiety

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Summary

Introduction

Ever since the 19th century case report of Phineas Gage, whose emotional character dramatically changed after considerable damage to his ventromedial prefrontal cortex, the PFC has been the focus of investigation for the regulation of emotions. Hypoactivation across the ventrolateral PFC (vlPFC) and orbitofrontal cortex (OFC) have been reported across different types of anxiety disorders (Etkin et al, 2007; Milad and Rauch, 2007; Killgore et al, 2013). These studies demonstrate significant association between prefrontal neural activities and pathological anxiety, in order to understand the etiology of these disorders, it is essential to establish the causal role of the prefrontal cortex in emotion regulation

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