Schielke Alexander, Krekelberg Bart
Center for Molecular and Behavioral Neuroscience, Rutgers University, Newark, NJ, USA.
Behavioral and Neural Sciences Graduate Program, Rutgers University, Newark, NJ, USA.
J Vis. 2021 Jun 7;21(6):9. doi: 10.1167/jov.21.6.9.
Visual cognition is finely tuned to the elements in a scene but also relies on contextual integration to improve visual detection and discrimination. This integration is impaired in patients with schizophrenia. Studying impairments in contextual integration may lead to biomarkers of schizophrenia, tools to monitor disease progression, and, in animal models, insight into the underlying neural deficits. We developed a nonhuman primate model to test the hypothesis that hypofunction of the N-methyl d-aspartate receptor (NMDAR) impairs contextual integration. Two male rhesus macaques (Macaca mulatta) were trained to indicate which of two patterns on the screen had the highest contrast. One of these patterns appeared in isolation, and the other was surrounded by a high-contrast pattern. In humans, this high-contrast context is known to lead to an underestimation of contrast. This so-called Chubb illusion is thought to result from surround suppression, a key contextual integration mechanism. To test the involvement of NMDAR in this process, we compared animals' perceptual bias with and without intramuscular injections of a subanesthetic dose of the NMDAR antagonist ketamine. In the absence of ketamine, the animals reported a Chubb illusion - matching reports in healthy humans. Hence, monkeys - just like humans - perform visual contextual integration. This reaffirms the importance of nonhuman primates to help understand visual cognition. Injection of ketamine significantly reduced the strength of the illusion and thus impaired contextual integration. This supports the hypothesis that NMDAR hypofunction plays a causal role in specific behavioral impairments observed in schizophrenia.
视觉认知能够精确地适应场景中的各种元素,但也依赖于上下文整合来提高视觉检测和辨别能力。这种整合能力在精神分裂症患者中受损。研究上下文整合方面的损伤可能会找到精神分裂症的生物标志物、监测疾病进展的工具,并且在动物模型中有助于深入了解潜在的神经缺陷。我们开发了一种非人类灵长类动物模型,以检验N-甲基-D-天冬氨酸受体(NMDAR)功能减退会损害上下文整合这一假设。我们训练了两只雄性恒河猴(猕猴),让它们指出屏幕上两种图案中对比度最高的是哪一个。其中一种图案单独出现,另一种则被高对比度图案包围。在人类中,已知这种高对比度背景会导致对对比度的低估。这种所谓的查布错觉被认为是由周边抑制引起的,周边抑制是一种关键的上下文整合机制。为了测试NMDAR在这一过程中的作用,我们比较了动物在肌肉注射亚麻醉剂量的NMDAR拮抗剂氯胺酮前后的感知偏差。在没有氯胺酮的情况下,动物表现出查布错觉——这与健康人类的报告一致。因此,猴子和人类一样,能够进行视觉上下文整合。这再次证明了非人类灵长类动物对于帮助理解视觉认知的重要性。注射氯胺酮显著降低了错觉的强度,从而损害了上下文整合。这支持了NMDAR功能减退在精神分裂症中观察到的特定行为损伤中起因果作用这一假设。