Causal Evidence for Lateral Prefrontal Cortex Dynamics Supporting Cognitive Control

The lateral prefrontal cortex (LPFC) is essential for higher-level cognition, but how interactions among LPFC areas support cognitive control has remained elusive. In previous work, dynamic causal modeling (DCM) of fMRI data revealed that demands on cognitive control elicited a convergence of influences towards mid LPFC. We proposed that these findings reflect the integration of abstract, rostral and concrete, caudal influences to inform context-appropriate action. Here, we provide a causal test of this model using continuous theta-burst transcranial magnetic stimulation (cTBS). cTBS was applied to caudal, mid, or rostral LPFC, as well as a control site in counterbalanced sessions. In most cases, behavioral modulations resulting from cTBS could be predicted based upon the direction of influences within the previously estimated DCM. However, inconsistent with our DCM, we found that cTBS to caudal LPFC impaired cognitive control processes presumed to involve rostral LPFC. Revising the original DCM with a pathway from caudal LPFC to rostral LPFC significantly improved the fitted DCM and accounted for the observed behavioral findings. These data provide causal evidence for LPFC dynamics supporting cognitive control and demonstrate the utility of combining DCM with causal manipulations to create, test, and refine models of cognition.