Neuronal firing rates account for distractor effects on mnemonic accuracy in a visuo-spatial working memory task.

Persistent neural activity constitutes one neuronal correlate of working memory, the ability to hold and manipulate information across time, a prerequisite for cognition. Yet, the underlying neuronal mechanisms are still elusive. Here, we design a visuo- spatial delayed-response task to identify the relationship between the cue-distractor spatial distance and mnemonic accuracy. Using a shared experimental and computational test protocol, we probe human subjects in computer experiments, and subsequently we evaluate different neural mechanisms underlying persistent activity using an in silico prefrontal network model. Five modes of action of the network were tested: weak or strong synaptic interactions, wide synaptic arborization, cellular bistability and reduced synaptic NMDA component. The five neural mechanisms and the human behavioral data, all exhibited a significant deterioration of the mnemonic accuracy with decreased spatial distance between the distractor and the cue. A subsequent computational analysis revealed that the firing rate and not the neural mechanism per se, accounted for the positive correlation between mnemonic accuracy and spatial distance. Moreover, the computational modeling predicts an inverse correlation between accuracy and distractibility. In conclusion, any pharmacological modulation, pathological condition or memory training paradigm targeting the underlying neural circuitry and altering the net population firing rate during the delay is predicted to determine the amount of influence of a visual distraction.