Effects of expectation, attention, and NMDA receptor blockade on feedforward and feedback processing

Abstract Perception is increasingly viewed as an inferential process wherein sensory inputs are integrated with prior expectations. We employed time-resolved decoding on electroencephalography (EEG) data (n = 30 male participants) to investigate how expectations modulate sensory processing across varying levels of stimulus complexity, and tested the effect of attention and NMDA receptor blockade. We designed a visual stimulus containing features of different complexity whose processing relies on distinct neural mechanisms: local contrast, collinearity, and the Kanizsa illusion, involving primarily feedforward, lateral, and feedback processes, respectively. EEG decoding revealed that expectations modulated lateral and feedback processing (better decoding for unexpected stimuli) but not feedforward processing. These expectation effects were confined to attended (task-relevant) features and were not observed for task-irrelevant features. The NMDA receptor antagonist memantine selectively enhanced decoding of the Kanizsa illusion, implicating NMDA-mediated feedback mechanisms in perceptual inference, but it did not modulate the effects of expectation or attention. These findings highlight the differential impact of expectations across different stages of sensory processing and reveal a distinct role of NMDA receptor-mediated feedback mechanisms. Significance statement Perception integrates sensory inputs with prior expectations. Using EEG decoding, we examined how expectations shape sensory processing at different levels of complexity and tested the effects of attention and NMDA receptor blockade. Our visual stimuli were designed to capture EEG markers of feedforward, lateral, and feedback mechanisms. Expectations influenced lateral and feedback processing (better decoding for unexpected stimuli) but not feedforward processing, and these effects were selective to task-relevant stimulus features. Memantine, an NMDA receptor antagonist, selectively improved decoding of the Kanizsa illusion, implicating NMDA-mediated feedback in perceptual inference, but it did not shape expectation or attention effects. Competing Interest Statement The authors have declared no competing interest. Footnotes ↵^ Shared senior authorship This research was supported by a grant from the H2020 European Research Council (ERC STG 715605, SVG).