Computational and neurobiological mechanisms underlying cognitive flexibility.

The ability to switch between multiple tasks is central to flexible behavior. Although switching between tasks is readily accomplished, a well established consequence of task switching (TS) is behavioral slowing. The source of this switch cost and the contribution of cognitive control to its resolution remain highly controversial. Here, we tested whether proactive interference arising from memory places fundamental constraints on flexible performance, and whether prefrontal control processes contribute to overcoming these constraints. Event-related functional MRI indexed neural responses during TS. The contributions of cognitive control and interference were made theoretically explicit in a computational model of task performance. Model estimates of two levels of proactive interference, "conceptual conflict" and "response conflict," produced distinct preparation-related profiles. Left ventrolateral prefrontal cortical activation paralleled model estimates of conceptual conflict, dissociating from that in left inferior parietal cortex, which paralleled model estimates of response conflict. These computationally informed neural measures specify retrieved conceptual representations as a source of conflict during TS and suggest that left ventrolateral prefrontal cortex resolves this conflict to facilitate flexible performance.