Robustness of working memory to prefrontal cortex microstimulation

Delay period activity in the dorso-lateral prefrontal cortex (dlPFC) has been linked to the maintenance and control of sensory information in working memory. The stability of working memory related signals found in such delay period activity is believed to support robust memory-guided behavior during sensory perturbations, such as distractors. Here, we directly probed dlPFCs delay period activity with a diverse set of activity perturbations, and measured their consequences on neural activity and behavior. We applied patterned microstimulation to the dlPFC of monkeys implanted with multi-electrode arrays by electrically stimulating different electrodes in the array while the monkeys performed a memory-guided saccade task. We found that the microstimulation perturbations affected spatial working memory-related signals in individual dlPFC neurons. However, task performance remained largely unaffected. These apparently contradictory observations could be understood by examining different dimensions of the dlPFC population activity. In dimensions where working memory related signals naturally evolved over time, microstimulation impacted neural activity. In contrast, in dimensions containing working memory related signals that were stable over time, microstimulation minimally impacted neural activity. This dissociation explained how working memory-related information could be stably maintained in dlPFC despite the activity changes induced by microstimulation. Thus, working memory processes are robust to a variety of activity perturbations in the dlPFC. Significance statementMemory-guided behavior is remarkably robust to sensory perturbations such as distractions. The dorso-lateral prefrontal cortex (dlPFC) is believed to underlie this robustness, given that it stably maintains working memory-related information in the presence of distractors. Here, we sought to understand the extent to which dlPFC circuits can robustly maintain working memory information during memory-guided behavior. We found that behavior was robust to microstimulation perturbations in dlPFC, and that working memory signals were stably maintained in dlPFC despite widespread changes in the neural activity caused by the perturbations. Our findings indicate that working memory is robust to direct activity perturbations in the dlPFC, an ability that may be due to the processes that mediate similar robustness in the face of distraction.