Schizophrenia is associated with severe cognitive deficits, including impaired working memory (WM). A neural mechanismthatmay contribute toWMimpairment is the disruption in excitation-inhibition (E/I) balance in cortical microcircuits. It remains unknown, however, how these alterations map onto quantifiable behavioral deficits in patients. Based on predictions from a validated microcircuit model of spatial WM, we hypothesized two key behavioral consequences: i) increased variability of WMtraces over time, reducing performance precision; and ii) decreased ability to filter out distractors that overlapwithWMrepresentations. To testmodel predictions, we studied N = 27 schizophrenia patients and N = 28 matched healthy comparison subjects (HCS) who performed a spatialWMtask designed to test the computational model. Specifically, we manipulated delay duration and distractor distance presented during the delay. Subjects used a high-sensitivity joystick to indicate the remembered location, yielding a continuous response measure. Results largely followedmodel predictions, whereby patients exhibited increased variance and less WM precision as the delay period increased relative to HCS. Schizophrenia patients also exhibited increasedWMdistractibility, with reports biased toward distractors at specific spatial locations, as predicted by the model. Finally, the magnitude of theWM drift and distractibility were significantly correlated, indicating a possibly shared underlying mechanism. Effects are consistent with elevated E/I ratio in schizophrenia, establishing a framework for translating neural circuit computational model of cognition to human experiments, explicitly testing mechanistic behavioral hypotheses of cellular-level neural deficits in patients. (C) 2016 Published by Elsevier B.V.