McDannald Michael, Schoenbaum Geoffrey
University of Maryland School of Medicine, Department of Anatomy and Neurobiology, Baltimore, MD 21201, USA.
Schizophr Bull. 2009 Jul;35(4):664-7. doi: 10.1093/schbul/sbp050. Epub 2009 May 21.
Schizophrenia is a chronic brain disorder that affects about 1.1% of the adult US population annually. Hallucinations, delusions, and impaired reality testing are prominent symptoms of the disorder. Modeling these symptoms is difficult because it is unclear how to assess impaired reality testing in animals. Animals cannot discuss their beliefs; however, a century of learning experiments has shown us that they, like us, construct complex internal representations of their world. Presumably, these representations can become confused with reality for animals in much the same way that they do for schizophrenic patients. Indeed, there is evidence from studies of Pavlovian conditioning that this happens even in normal animals. For example, early in training a cue that has been paired with reward elicits a highly realistic, sensory representation of that reward, which is to some extent indistinguishable from reality. With further training, this sensory hallucination of reward is replaced by a more abstract representation, termed a reward expectancy. Reward expectancies reflect the sensory and other qualities of the impending reward but are distinguishable from the actual reward. Notably, the hallucinatory representations depend on subcortical regions, such as amygdala, whereas reward expectancies require the progressive involvement of prefrontal areas, such as orbitofrontal cortex. Abnormal prefrontal function is associated with schizophrenia; impaired reality testing may result from a failure of the normal shift from highly realistic, sensory representations to more abstract, prefrontal expectancies. The Pavlovian procedures discussed here could be applied to animal models and schizophrenic patients to test this hypothesis.
精神分裂症是一种慢性脑部疾病，每年影响约1.1%的美国成年人口。幻觉、妄想和现实检验受损是该疾病的突出症状。对这些症状进行建模很困难，因为尚不清楚如何在动物身上评估现实检验受损情况。动物无法谈论它们的信念；然而，一个世纪的学习实验表明，它们和我们一样，构建了关于其世界的复杂内部表征。据推测，这些表征在动物身上可能会与现实混淆，就像在精神分裂症患者身上一样。事实上，来自巴甫洛夫条件反射研究的证据表明，即使在正常动物身上也会发生这种情况。例如，在训练初期，与奖励配对的线索会引发对该奖励高度逼真的感官表征，在某种程度上与现实难以区分。随着进一步训练，这种奖励的感官幻觉会被一种更抽象的表征所取代，称为奖励预期。奖励预期反映了即将到来的奖励的感官和其他特征，但与实际奖励是可区分的。值得注意的是，幻觉表征依赖于杏仁核等皮层下区域，而奖励预期则需要眶额皮层等前额叶区域的逐步参与。前额叶功能异常与精神分裂症有关；现实检验受损可能是由于从高度逼真的感官表征到更抽象的前额叶预期的正常转变失败所致。这里讨论的巴甫洛夫程序可应用于动物模型和精神分裂症患者来检验这一假设。
