Noorman Samuel, Stein Timo, Zantvoord Jasper, Fahrenfort Johannes, van Gaal Simon
Department of Psychology, University of Amsterdam, Amsterdam, Netherlands.
Amsterdam Brain and Cognition, University of Amsterdam, Amsterdam, Netherlands.
Elife. 2025 Jun 18;13:RP100530. doi: 10.7554/eLife.100530.
Perceptual inference requires the integration of visual features through recurrent processing, the dynamic exchange of information between higher- and lower-level cortical regions. While animal research has demonstrated a crucial role of NMDA receptors in recurrent processing, establishing a causal link between NMDA receptors and recurrent processing in humans has remained challenging. Here, we report two pharmacological studies with randomized, double-blind, crossover designs in which we administered the NMDA antagonist memantine, while collecting human electroencephalography (EEG). We trained and tested EEG classifiers to reflect the processing of specific stimulus features with increasing levels of complexity, namely differences in stimulus contrast, collinearity between local line elements, and illusory surfaces of a Kanizsa triangle. In two experiments involving different participants and visual tasks, we found that memantine selectively improved decoding of the Kanizsa illusion, known to depend on recurrent processing, while leaving decoding of contrast and collinearity largely unaffected. Interestingly, the results from an attentional blink (experiment 1) and task-relevance manipulation (experiment 2) showed that memantine was only effective when the stimulus was attended and consciously accessed. These findings suggest that NMDA inhibition through memantine enhances recurrent processing, especially for attended objects, and thereby provide a crucial step toward bridging animal and human research, shedding light on the neural mechanisms underpinning perceptual inference and conscious perception.
知觉推理需要通过循环处理来整合视觉特征，即高低级皮层区域之间信息的动态交换。虽然动物研究已经证明了NMDA受体在循环处理中的关键作用，但在人类中建立NMDA受体与循环处理之间的因果联系仍然具有挑战性。在此，我们报告两项采用随机、双盲、交叉设计的药理学研究，在研究中我们给予NMDA拮抗剂美金刚，同时收集人类脑电图（EEG）。我们训练并测试EEG分类器，以反映随着刺激特征复杂度增加对特定刺激特征的处理，即刺激对比度差异、局部线条元素之间的共线性以及卡尼兹三角的虚幻表面。在涉及不同参与者和视觉任务的两项实验中，我们发现美金刚选择性地改善了已知依赖循环处理的卡尼兹错觉的解码，而对比和共线性的解码基本未受影响。有趣的是，注意瞬脱（实验1）和任务相关性操作（实验2）的结果表明，美金刚仅在刺激被关注并被有意识地感知时才有效。这些发现表明，通过美金刚抑制NMDA可增强循环处理，尤其是对被关注物体的循环处理，从而为弥合动物研究和人类研究之间的差距迈出了关键一步，揭示了支撑知觉推理和意识感知的神经机制。
