The prefrontal cortex is among the last regions of the brain to develop, in evolution and in individual maturation. In the human, it constitutes nearly one-third of the totality of the neocortex. The most recent prefrontal cortex (pole and lateral convexity of the frontal lobe) is layered and granular, with a distinct layer IV which is heavily populated by granular cells. The more primitive, phylogenetically earlier, ventral and medial prefrontal cortex is dysgranular, poorly layered, and structurally and functionally akin to limbic cortex. Anatomically defined by its connectivity with the nucleus medialis dorsalis of the thalamus, the prefrontal cortex is the best connected of all neocortical regions. It is reciprocally connected, directly or indirectly, with the posterior association cortex, thalamus, hypothalamus, amygdala, basal ganglia, insula, hippocampus, cerebellum, and brainstem.