History-dependent Biases in Perceptual Decisions Depend on NMDA Receptors

Perceptual decisions are governed not only by current sensory input but also by the history of previous stimuli, choices, or outcomes. Such history-dependent biases evolve across multiple timescales ranging from seconds to minutes. Synaptic plasticity is one possible mechanism mediating such effects. The by N-methyl-aspartate (NMDA) glutamate receptor is critical for synaptic plasticity, and indirect evidence points to its role in the generation of history-dependent biases. Here, we pharmacologically blocked NMDA receptors in healthy human participants performing a two-alternative visual decision-making task. Participants choices were biased by the accumulation of fluctuating sensory evidence within each trial as well as the accumulation of across-trial sequences of stimuli, which enabled them to adapt to changing stimulus statistics across blocks. NMDA receptor blockade reduced the task-adaptive across trials, history-dependent biases. In contrast, enhancing GABA-A receptor activity in the same participants increased the transiency of the within-trial evidence accumulation dynamics. Our findings provide direct evidence for the importance of NMDA receptor function in history-dependent biases in the human brain.