PROJECT SUMMARY The proposed study will investigate the role of persistent activity of the lateral prefrontal cortex in object working memory using a non-human primate model. Persistent activity of the prefrontal cortex has long been speculated as the neural correlate of working memory. In recent years alternative models have been proposed, particularly for object working memory. We hypothesize that persistent activity plays a causal role in reflecting the features of remembered stimuli, rather merely representing parameters of the task that subjects perform or highlighting the spatial location of remembered objects. Rhesus macaques will thus be trained in a feature working memory task that will require them to remember and make judgments about visual stimuli. We will record neural activity with a chronic array of microelectrodes, distributed across the surface of the lateral prefrontal cortex, both before and after training. We will test whether the peak of population activity can explain what stimulus the monkeys ultimately remember, and whether drift of this peak of activity over time predicts errors. We will additionally determine how neuronal responses are affected by training by using familiar and novel stimuli in the context of the same working memory task. Moreover, we will directly test the causality of this persistent activity by applying microsimulation on carefully selected electrodes, to cause the animals to erroneously recall not the actual stimulus presented, but the preferred stimulus of the site being stimulated. As a result, the proposed experiments will determine the specific, causal mechanisms in the prefrontal cortex that are ultimately responsible for mediating visual working memory.