Moderate excitation leads to weakening of perceptual representations.

A fundamental goal of memory research is to specify the conditions that lead to the strengthening and weakening of neural representations. Several computational models of memory formation predict that learning effects should vary as a nonmonotonic function of the amount of excitation received by a neural representation. Specifically, moderate excitation should result in synaptic weakening, while strong excitation should result in synaptic strengthening. In vitro investigations of plasticity in rodents have provided support for this prediction at the level of single synapses. However, it remains unclear whether this principle scales beyond the synapse to cortical representations and manifests changes in behavior. To address this question, we used electroencephalogram pattern classification in human subjects to measure trial-by-trial fluctuations in stimulus processing, and we used a negative priming paradigm to measure learning effects. In keeping with the idea that moderate excitation leads to weakening, moderate levels of stimulus processing were associated with negative priming (slower subsequent responding to the stimulus), but higher and lower levels of stimulus processing were not associated with negative priming. These results suggest that the same principles that account for synaptic weakening in rodents can also account for diminished accessibility of perceptual representations in humans.