Lesions of the medial striatum in monkeys produce perseverative impairments during reversal learning similar to those produced by lesions of the orbitofrontal cortex.
Lesions of the medial striatum in monkeys produce perseverative impairments during reversal learning similar to those produced by lesions of the orbitofrontal cortex.
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DOI：
10.1523/jneurosci.1521-08.2008
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发表时间：
2008-10-22
期刊：
影响因子：
--
通讯作者：
Roberts AC
中科院分区：
文献类型：
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作者：
Clarke HF;Robbins TW;Roberts AC
根据两种视觉刺激与奖励的关系变化而在两种视觉刺激之间切换反应的能力依赖于眶额皮质（OFC）。人类、猴子和大鼠的OFC病变破坏了这种能力的常见测试——视觉序列识别逆转任务的表现。这一发现对我们理解精神疾病，如强迫症（OCD）和精神分裂症，具有特别重要的意义，其中行为不灵活是一个突出的症状。尽管OFC功能障碍可能发生在这些疾病中，但有相当多的证据表明，额纹状体和额杏仁核回路的功能障碍更为广泛。由于这些皮质下结构对行为灵活性的贡献尚不清楚，本研究比较了绒猴内侧纹状体（MS）、杏仁核和OFC的兴奋性毒性病变对一系列逆转任务表现的影响。所有的猴子都能够学习一种新的刺激-奖励联系，但是，与对照组和杏仁核受损的猴子相比，那些患有MS或OFC损伤的猴子在逆转这种联系的能力上表现出持久性损伤。然而，MS组和OFC组对负反馈不敏感，只有OFC损伤的猴子对正反馈不敏感。这些发现表明，由于不同的原因，MS和OFC都支持奖励随变变化后的行为灵活性，并且与纹状体和OFC功能障碍可能导致病理性坚持的假设一致。
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.