与纹状体多巴胺相关的幻觉的知觉推断机制。

A Perceptual Inference Mechanism for Hallucinations Linked to Striatal Dopamine.

机构信息

Department of Psychiatry, New York State Psychiatric Institute, Columbia University Medical Center, 1051 Riverside Drive, New York, NY 10032, USA; The Royal's Institute of Mental Health Research, University of Ottawa, 1145 Carling Avenue, Ottawa, ON K1Z 7K4, Canada.

Department of Psychiatry, New York State Psychiatric Institute, Columbia University Medical Center, 1051 Riverside Drive, New York, NY 10032, USA; Department of Psychology, Columbia University, 3009 Broadway, New York, NY 10027, USA.

出版信息

Curr Biol. 2018 Feb 19;28(4):503-514.e4. doi: 10.1016/j.cub.2017.12.059. Epub 2018 Feb 2.

Abstract

Hallucinations, a cardinal feature of psychotic disorders such as schizophrenia, are known to depend on excessive striatal dopamine. However, an underlying cognitive mechanism linking dopamine dysregulation and the experience of hallucinatory percepts remains elusive. Bayesian models explain perception as an optimal combination of prior expectations and new sensory evidence, where perceptual distortions such as illusions and hallucinations may occur if prior expectations are afforded excessive weight. Such excessive weight of prior expectations, in turn, could stem from a gain-control process controlled by neuromodulators such as dopamine. To test for such a dopamine-dependent gain-control mechanism of hallucinations, we studied unmedicated patients with schizophrenia with varying degrees of hallucination severity and healthy individuals using molecular imaging with a pharmacological manipulation of dopamine, structural imaging, and a novel task designed to measure illusory changes in the perceived duration of auditory stimuli under different levels of uncertainty. Hallucinations correlated with a perceptual bias, reflecting disproportional gain on expectations under uncertainty. This bias could be pharmacologically induced by amphetamine, strongly correlated with striatal dopamine release, and related to cortical volume of the dorsal anterior cingulate, a brain region involved in tracking environmental uncertainty. These findings outline a novel dopamine-dependent mechanism for perceptual modulation in physiological conditions and further suggest that this mechanism may confer vulnerability to hallucinations in hyper-dopaminergic states underlying psychosis.

摘要

幻觉是精神分裂症等精神障碍的主要特征,已知其与纹状体多巴胺的过度增加有关。然而,将多巴胺失调与幻觉知觉的体验联系起来的潜在认知机制仍然难以捉摸。贝叶斯模型将感知解释为先前期望和新感觉证据的最佳组合,如果先前的期望被赋予过大的权重,就会出现感知扭曲,如错觉和幻觉。这种先前期望的过度权重,反过来又可能源于由神经调质(如多巴胺)控制的增益控制过程。为了测试幻觉的这种多巴胺依赖的增益控制机制,我们使用一种药理学操纵多巴胺的分子成像、结构成像以及一项旨在测量在不同不确定性水平下听觉刺激感知持续时间的幻觉变化的新任务,研究了不同幻觉严重程度的未用药精神分裂症患者和健康个体。幻觉与感知偏差相关,反映了不确定性下期望的不成比例的增加。这种偏差可以通过安非他命(amphetamine)引发,与纹状体多巴胺释放强烈相关,并与背侧前扣带回(dorsal anterior cingulate)的皮质体积有关,背侧前扣带回是一个参与跟踪环境不确定性的大脑区域。这些发现概述了一种在生理条件下进行感知调节的新型多巴胺依赖机制,并进一步表明,这种机制可能使处于精神病高多巴胺状态下的人容易出现幻觉。

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