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Researchers Target Two Brain Sites Responsible For Anxiety

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Fear and anxiety are synonymous but there is a subtle difference between them when these terms are used scientifically. Fear is the response to an immediate actual threat meanwhile; anxiety is the fear that rises from expectation of the future. Today, scientists understand the typical anxiety disorder symptoms and also know how to treat those symptoms. But, what still remains challenging is the study of the neurology of anxiety. For example, it is known to the scientists that dysregulation of the orbitofrontal and ventrolateral prefrontal cortices are involved in such disorders, but it is known fully understood which are the specific contributions of each region.

A study was designed by a group of researchers at the University of Cambridge to assess the contributions of these regions of the brain in the anxiety responses of marmosets. Their findings were published in the Proceedings of the National Academy of Sciences.

Overreaction to Threat Conditions:

Anxiety and fear of unfavorable outcomes affects decision making in a person in a negative way. It often leads to stress, isolation and adverse health condition. It is important that an organism is threat for survival, but hypersensitivity to threat inhibit the right decision making capability in patients. There have been studies in the past which have suggested that this hypersensitivity is a result of dysregulation within the prefrontal cortex. However, it is not fully understood how this region affects aversive processing and how it has an impact on the negative emotional valence in decision making.

Since, it is known that the excitotoxic lesions on either the anterior orbitofrontal cortex or ventrolateral prefrontal cortex elevates anxiety and fear responses in marmosets, researchers designed an experiment to test on monkeys to study their responses before and after temporary inactivation of these regions.

Testing the Brain’s Threat Prediction Ability

The marmosets for the test were trained to respond to two identical visual stimuli. These stimuli were presented on each side of a touchscreen to gain a reward of banana juice. The way the visual stimuli were presented were independent but had identical variable-interval schedules. The response biases of individual monkeys were observed and it was seen that each monkey demonstrated a slight bias for one side of the screen or the other. Once per week, responses on one of the two stimuli would produce delivery of a punishment in the form of an aversive loud noise that was superimposed on the unchanged reward schedule. Such that spatial bias contributing to a punishment-induced bias could be avoided, the punishment was always introduced on the individual monkey’s “preferred” side.

It was seen that in the absence of reward, the punishment produced a strong aversive response. But, when the punishment and reward were delivered simultaneously, the monkeys did not alter their behavior. Hence, it was concluded by the researchers that the monkeys perceived the banana juice reward “worth” responding for, even though there was a possibility of the punishment.

The researchers then carried out the same experiment after inactivating either the anterior orbitofrontal cortex or ventrolateral prefrontal cortex with a GABA agonist 20 minutes before test sessions. It was seen that the inactivation of one of the two regions had no effect on responses when the test ended in a reward but no punishment. However, when punishment was introduced for responses, the monkeys with inactivated ventrolateral interior prefrontal cortex produced a strong, immediate response bias away from the punishment. These animals when tested again the next day for a reward only session did not show any anomaly from the previous behavior. So, it was understood that the bias developed in test animals during the reward-punishment sessions, but did not endure. But, it was seen that the animals with inactivated anterior orbitofrontal cortices showed did show a profound bias away from the previously punished side the next day. Thus, the researchers associate the activity of the vlPFC with cost-benefit analyses and the antOFC with the consolidation of memory for the punishment.

The researchers are of the opinion that in the future; cognitive behavioral therapy for patients suffering from anxiety disorders could be tailored according to the patient’s ability to make accurate cost-benefit analyses or to form memories that lead to strong antipunishment biases.

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