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The Journal of Neuroscience, October 22, 2008, 28(43):10972-10982; doi:10.1523/JNEUROSCI.1521-08.2008

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Behavioral/Systems/Cognitive
Lesions of the Medial Striatum in Monkeys Produce Perseverative Impairments during Reversal Learning Similar to Those Produced by Lesions of the Orbitofrontal Cortex

Hannah F. Clarke,^1,2 Trevor W. Robbins,^1,2 and Angela C. Roberts^2,3

¹Department of Experimental Psychology and ²Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge CB2 3EB, United Kingdom, and ³Department of Physiology, Development, and Neuroscience, University of Cambridge, Cambridge CB2 3DY, United Kingdom

Correspondence should be addressed to Hannah F. Clarke, Department of Experimental Psychology, University of Cambridge, Downing Street, Cambridge CB2 3EB, UK. Email: hfc23{at}cam.ac.uk

The ability to switch responding between two visual stimuli based on their changing relationship with reward is dependent on the orbitofrontal cortex (OFC). OFC lesions in humans, monkeys, and rats disrupt performance on a common test of this ability, the visual serial discrimination reversal task. This finding is of particular significance to our understanding of psychiatric disorders such as obsessive–compulsive disorder (OCD) and schizophrenia, in which behavioral inflexibility is a prominent symptom. Although OFC dysfunction can occur in these disorders, there is considerable evidence for more widespread dysfunction within frontostriatal and frontoamygdalar circuitry. Because the contribution of these subcortical structures to behavioral flexibility is poorly understood, the present study compared the effects of excitotoxic lesions of the medial striatum (MS), amygdala, and OFC in the marmoset monkey on performance of the serial reversal task.

All monkeys were able to learn a novel stimulus–reward association but, compared with both control and amygdala-lesioned monkeys, those with MS or OFC lesions showed a perseverative impairment in their ability to reverse this association. However, whereas both MS and OFC groups showed insensitivity to negative feedback, only OFC-lesioned monkeys showed insensitivity to positive feedback. These findings suggest that, for different reasons, both the MS and OFC support behavioral flexibility after changes in reward contingencies, and are consistent with the hypothesis that striatal and OFC dysfunction can contribute to pathological perseveration.

Key words: striatum; prefrontal cortex; feedback; extinction; amygdala; cognition

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Received April 8, 2008; revised Sept. 10, 2008; accepted Sept. 18, 2008.

Correspondence should be addressed to Hannah F. Clarke, Department of Experimental Psychology, University of Cambridge, Downing Street, Cambridge CB2 3EB, UK. Email: hfc23{at}cam.ac.uk

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