Neural markers of errors as endophenotypes in neuropsychiatric disorders.
Neural markers of errors as endophenotypes in neuropsychiatric disorders.
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DOI：
10.3389/fnhum.2013.00350
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发表时间：
2013
影响因子：
2.9
通讯作者：
Agam Y
中科院分区：
文献类型：
--
作者：
Manoach DS;Agam Y
从错误中学习是适应性人类行为的基础。它需要发现错误，评估出了什么问题，并相应地调整行为。这些动态调整是行为灵活性的核心，越来越多的证据表明，错误处理不足导致了一系列神经精神疾病中的适应不良的僵化和重复行为。神经影像学和电生理学研究揭示了高度可靠的错误处理的神经标记。在这篇综述中，我们评估的证据表明，这些神经标志物的异常可以作为敏感的神经精神疾病的内表型。我们描述了错误处理的行为和神经特征，常见的遗传多态性对它们的调节，以及精神分裂症、强迫症和自闭症谱系障碍的损害。我们的结论是，神经标志物的错误，满足几个重要的标准，包括遗传性，建立神经解剖和神经化学基板，与神经精神疾病，存在于综合征未受影响的家庭成员，遗传中介的证据。了解神经精神疾病中错误处理缺陷的机制可能为治疗提供新的神经和行为靶点，并提供敏感的治疗反应替代标记物。治疗错误处理缺陷可以改善功能结果，因为错误信号提供了灵活适应不断变化的环境的关键信息。鉴于缺乏有效的干预措施，在神经精神疾病的认知缺陷，这是一个潜在的有前途的方法。
Learning from errors is fundamental to adaptive human behavior. It requires detecting errors, evaluating what went wrong, and adjusting behavior accordingly. These dynamic adjustments are at the heart of behavioral flexibility and accumulating evidence suggests that deficient error processing contributes to maladaptively rigid and repetitive behavior in a range of neuropsychiatric disorders. Neuroimaging and electrophysiological studies reveal highly reliable neural markers of error processing. In this review, we evaluate the evidence that abnormalities in these neural markers can serve as sensitive endophenotypes of neuropsychiatric disorders. We describe the behavioral and neural hallmarks of error processing, their mediation by common genetic polymorphisms, and impairments in schizophrenia, obsessive-compulsive disorder, and autism spectrum disorders. We conclude that neural markers of errors meet several important criteria as endophenotypes including heritability, established neuroanatomical and neurochemical substrates, association with neuropsychiatric disorders, presence in syndromally-unaffected family members, and evidence of genetic mediation. Understanding the mechanisms of error processing deficits in neuropsychiatric disorders may provide novel neural and behavioral targets for treatment and sensitive surrogate markers of treatment response. Treating error processing deficits may improve functional outcome since error signals provide crucial information for flexible adaptation to changing environments. Given the dearth of effective interventions for cognitive deficits in neuropsychiatric disorders, this represents a potentially promising approach.
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