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

doi:10.1016/j.biopsych.2012.03.007

Biological Psychiatry

Volume 72, Issue 4, 15 August 2012, Pages 266-272

https://doi.org/10.1016/j.biopsych.2012.03.007 Get rights and content

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.

Section snippets

Methods and Materials

All procedures were conducted in accordance with the United Kingdom 1986 Animals (Scientific Procedures) Act under project license PPL 80/2225.

An Enhanced and More Rigid Expression of Conditioned Fear Responses After Excitotoxic Lesions of Either vlPFC or antOFC

Because groups were counterbalanced for learning rate and strength of conditioning (Figure S2 and Table S2 in Supplement 1), there were no group differences pre-operatively in acquiring discriminative Pavlovian conditioning (Figure 2A). One way ANOVAs for sessions to criterion and conditioned HR and vigilant scanning at criterion revealed no significant effects (F values < 1).

Postoperatively, all animals from control, vlPFC, and antOFC lesioned groups (except one antOFC lesioned animal that

Discussion

Abnormal fear and anxiety responses are characteristic of the human disorders of mood and anxiety and have been associated with alterations in activity and gray matter volume within the ventral PFC of patients suffering from these disorders (1, 2, 3). In the present study selective excitotoxic lesions of either vlPFC or antOFC in monkeys resulted in heightened anxiety and more rigid, less adaptable conditioned fear responses, effects akin to those reported in anxiety disorders (29, 30). These

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: Authors KB and YS contributed equally to this work.

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

Background

Methods

Results

Conclusions

Section snippets

Methods and Materials

An Enhanced and More Rigid Expression of Conditioned Fear Responses After Excitotoxic Lesions of Either vlPFC or antOFC

Discussion

Curr Opin Neurobiol

Biol Psychiatry

Curr Opin Neurobiol

Cortex

Psychoneuroendocrinology

Biol Psychiatry

Pharmacol Biochem Behav

Neurosci Biobehav Rev

Biol Psychiatry

Neuroimage

Neurobiol Learn Mem

Neuron

Neuroimage

Neurosci Biobehav Rev

Brain Res

Neuron

Neuroimage

The role of the orbitofrontal cortex in anxiety disorders

Ann N Y Acad Sci

Neurocircuitry of mood disorders

Neuropsychopharmacology

The organization of networks within the orbital and medial prefrontal cortex of rats, monkeys and humans

Cereb Cortex

Alterations in aversive and aggressive behaviors following orbital frontal lesions in rhesus monkeys

Acta Neurobiol Exp (Wars)

Effects of orbital frontal lesions on aversive and aggressive behaviors in rhesus monkeys

J Comp Physiol Psychol

Differential role of the medial and lateral prefrontal cortices in fear and anxiety

Behav Neurosci

Distinct contributions of frontal areas to emotion and social behaviour in the rat

Eur J Neurosci

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