The Necessity of Rostrolateral Prefrontal Cortex for Higher-Level Sequential Behavior.

Frontal neocortex is thought to support our highest intellectual abilities, including our ability to plan and enact a sequence of tasks toward a desired goal. In everyday life, such task sequences are abstract in that they do not require consistent movement sequences and are often assembled "on the fly." Yet, remarkably little is known about the necessity of frontal sub-regions for such control. Participants repeatedly completed sequences of simple tasks during fMRI scanning. Rostrolateral prefrontal cortex (RLPFC) activation ramped over sequence position and reset at the initiation of each new sequence. To establish the necessity and function of RLPFC in this task, participants performed the sequential task while undergoing transcranial magnetic stimulation (TMS) of the RLPFC versus two prefrontal control regions. Across two independent experiments, only RLPFC stimulation increasingly disrupted task performance as each sequence progressed. These data establish RLPFC as necessary for uncertainty resolution during sequence-level control.