Introduction: Deficit in cognitive flexibility has been observed in several mental and brain disorders. The dorsolateral prefrontal cortex is the most important brain region involved in cognitive flexibility related tasks. Using a computer model of neuronal stimulation, the aim of this study was to investigate the effects of manipulating neural activity in this brain region on cognitive flexibility. Materials and Methods: A computer simulation approach was used. Simulation was in the context of Leabra cognitive architecture and by using PBWM model was implemented. Results: This study shows that increasing neural activity in the dorsal lateral prefrontal cortex linearly decreased cognitive flexibility. In addition, reduction of neural activity in this region of the brain decreased cognitive flexibility in a larger extent. Conclusion: These data indicate that hypo- or hyperactivity of inhibitory interneurons in the dorsal lateral prefrontal cortex can cause deficit in cognitive flexibility. Manipulation of neural activity in this region can distinguish two subgroups of patients with impaired cognitive flexibility.