.. Executive control, rules, and the prefrontal cortex By definition, controlled thought and action are goal-directed and organized toward the completion of tasks. Consider a common cognitively demanding situation: navigating an airport. From the start, we know that we need a ticket, have to wait in line, board at the right

gate, etc. We are not born knowing this; we have to learn the rules. As such, the neural substrates for executive control need to have access to the wide range of information needed to identity potential goals and the rules that can achieve them. This no doubt Inhibitors,research,lifescience,medical depends on many different brain areas. However, one cortical region is particularly necessary (but not sufficient): the PFC. It is this cortical area that reaches the greatest relative size in the human brain and is thus thought to be the neural instantiation of the mental qualities that we think of as “intelligent.” The PFC is anatomically well situated to play a role as the brain’s executive. It receives information from, and sends projections to, forebrain systems that Inhibitors,research,lifescience,medical process information about the external world, motor system structures that produce voluntary movement, systems that consolidate long-term memories, and systems that process information about affect and motivational state.2-5 This anatomy has long suggested that the PFC may be Kinase Inhibitor Library important for synthesizing Inhibitors,research,lifescience,medical the external and internal information needed to produce complex behavior.

Neurophysiological studies suggest that this synthesis serves to form representations of task rules (for reviews see refs 6-8). This has been shown in studies that systematically vary task demands; subjects perform a different set of operations Inhibitors,research,lifescience,medical or make different decisions using the same set of sensory Inhibitors,research,lifescience,medical inputs and motor options. For example, in one trial the subject may have to choose one of two pictures that matches one

seen previously (a match rule); in another trial the subject has to choose the nonmatching picture (a nonmatch rule).9 These types of experiments have revealed that the PFC neural activity is highly sensitive to rule information. In fact, unlike sensory cortex, especially primary sensory cortex, it appears that task rules are more influential on how information is distributed across PFC neurons Oxygenase than bottom-up sensory information. More neurons reflect task demands than sensor information, indeed often at the expense of sensory information.10-11 Interestingly, cognitively demanding tasks engage a very large proportion of PFC neurons; after training, as many as 30% to 40% of randomly selected PFC neurons show task-related activity.9,12-15 So many PFC neurons (one third or more of the population) dedicated to a given rule might, at first blush, make it seem as if the PFC can only learn a few tasks. If the one third of PFC neurons represent the rules of one task, does that mean that only three tasks can be learned? In fact the opposite is true.