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Published on: January 22, 2016
Deep brain stimulation in the lateral orbitofrontal cortex impairs spatial reversal learning
Marianne Klanker1, Ger Post, Ruud Joosten
1Netherlands Institute for Neuroscience, Institute of the Royal Netherlands Academy of Arts and Sciences, Meibergdreef 47, 1105 BA Amsterdam, The Netherlands. marianneklanker@yahoo.com
Abstract:
Deep Brain Stimulation (DBS) is a successful novel treatment for treatment-resistant obsessive-compulsive disorder and is currently under investigation for addiction and eating disorders. Clinical and preclinical studies have shown functional changes in the orbitofrontal cortex (OFC) following DBS in the ventral capsule/ventral striatum. These findings suggest that DBS can affect neural activity in distant regions that are connected to the site of electrode implantation. However, the behavioral consequences of direct OFC stimulation are not known. Here, we studied the effects of direct stimulation in the lateral OFC on spatial discrimination and reversal learning in rats. Rats were implanted with stimulating electrodes and were trained on a spatial discrimination and reversal learning task. DBS in the OFC did not affect acquisition of a spatial discrimination. Stimulated animals made more incorrect responses during the first reversal. Acquisition of the second reversal was not affected. These results suggest that DBS may inhibit activity in the OFC, or may disrupt output of the OFC to other cortical or subcortical areas, resulting in perseverative behavior or an inability to adapt behavior to altered response-reward contingencies.
Insights
Deep Brain Stimulation (DBS) in the orbitofrontal cortex (OFC) did not affect initial learning but impaired reversal learning in rats. This suggests DBS may disrupt OFC function, impacting behavioral flexibility.
Area of Science:
- Neuroscience
- Behavioral Science
- Neuromodulation
Background:
- Deep Brain Stimulation (DBS) is a novel treatment for psychiatric disorders, showing functional changes in the orbitofrontal cortex (OFC) after ventral striatal stimulation.
- Previous research indicates DBS can influence distant connected brain regions, but the effects of direct OFC stimulation on behavior remain unknown.
Purpose of the Study:
- To investigate the behavioral consequences of direct lateral orbitofrontal cortex (OFC) stimulation.
- To examine the impact of OFC DBS on spatial discrimination and reversal learning in a rat model.
Main Methods:
- Rats were surgically implanted with electrodes for direct stimulation in the lateral OFC.
- The animals were trained on a spatial discrimination and reversal learning task to assess behavioral adaptation.
- Behavioral performance, including acquisition and reversal phases, was analyzed under OFC DBS conditions.
Main Results:
- Direct OFC stimulation did not alter the acquisition of the initial spatial discrimination task.
- Rats receiving OFC DBS exhibited increased incorrect responses during the first reversal learning phase.
- The acquisition of the second reversal phase was not significantly affected by OFC stimulation.
Conclusions:
- Direct OFC stimulation may inhibit neural activity or disrupt its output pathways, leading to perseverative behavior.
- OFC DBS appears to impair the ability to adapt behavior in response to changing reward contingencies, specifically during reversal learning.
- These findings highlight the OFC's critical role in behavioral flexibility and adaptive responding.
