(A) Neuromodulatory projections of the ascending arousal system project divergent axons across the cortex, including to L6b, providing state-dependent signals. Likewise, higher-order cortical axons project to multiple cortical regions, including L6b, providing top-down volitional signals. L6b integrates the convergent input from these two pathways and directs its output to CTC loops with fast and focused activation.

(B) L6b is depolarized by arousal-promoting neuromodulators (left), and we hypothesize that the addition of higher-order cortical feedback strongly activates L6b (right). Thus, the role of neuromodulation is to bring L6b close to the activation threshold across the cortex so that specific L6b circuits can be more easily recruited by specific top-down cortical input. ACh, acetylcholine; 5HT, serotonin; DA, dopamine; NA, noradrenaline; HIS, histamine.