From ideas to action: The prefrontal-premotor connections that shape motor behavior

The prefrontal cortex serves a critical role in the coordination and execution of motor actions via its involvement in goal setting, decision-making, motivation, and cognitive control. Using the macaque connectome, the anatomic pathways from prefrontal cortex to motor circuitry are summarized, revealing a remarkably limited set of direct connections. A highly similar connectivity pattern is inferred from human neuroimaging. The results motivate the prefrontal-premotor connector hub model, which highlights both functional segregation and a limited set of connector hub regions that provide a direct linking of prefrontal cortex to the (pre-)motor network. Moreover, the macaque connectome reveals a set of motor translator regions that provide the most direct projection from premotor to prefrontal areas. The connector hub model leads to important functional implications: Neural activation or disruption in connector hubs should lead to functional deficits that undermine integration between higher cognitive action control and motor performance ranging from response selection and inhibition to perceived agency of actions. Segregation of prefrontal-premotor networks challenges hierarchical models of motor control and underscores the critical role of the indirect pathway from prefrontal to premotor areas via the parietal cortex. The model provides a predictive framework to design neurostimulation paradigms for modulating skill learning or recovery in both healthy subjects and patient cohorts.