Past Makes Future: Role of pFC in Prediction Joaquín M. Fuster 1 and Steven L. Bressler 2 Abstract ■ The pFC enables the essential human capacities for pre- dicting future events and preadapting to them. These capacities rest on both the structure and dynamics of the human pFC. Structurally, pFC, together with posterior association cortex, is at the highest hierarchical level of cortical organization, harbor- ing neural networks that represent complex goal-directed actions. Dynamically, pFC is at the highest level of the perception–action cycle, the circular processing loop through the cortex that inter- faces the organism with the environment in the pursuit of goals. In its predictive and preadaptive roles, pFC supports cognitive functions that are critical for the temporal organization of future behavior, including planning, attentional set, working memory, decision-making, and error monitoring. These functions have a common future perspective and are dynamically intertwined in goal-directed action. They all utilize the same neural infra- structure: a vast array of widely distributed, overlapping, and interactive cortical networks of personal memory and semantic knowledge, named cognits, which are formed by synaptic rein- forcement in learning and memory acquisition. From this cortex- wide reservoir of memory and knowledge, pFC generates purposeful, goal-directed actions that are preadapted to predicted future events. ■ INTRODUCTION With the extraordinary development of the pFC in evolu- tion, the human brain has gained the capacity to make future predictions far beyond that of any other animal species. pFC provides the brain with the ability not only to adapt the organism reactively to its environment but also to preadapt proactively to it. Thus, pFC makes the human brain self-predictive, enabling it to generate be- havioral changes and to preadapt to them. Preadaptation allows the fulfillment of an immense variety of personal purposes that transcend procreation and survival. Each relies on precedent, prediction, and preparation; here the prefix “pre” implies a prospective (future-oriented) temporal connotation. In short, one may state allegori- cally that evolution of pFC has endowed humans with the sense and command of their future. The concept of the future orientation of pFC has a long history. After WWI, German and Russian neurologists (Choroschko, 1923; Feuchtwanger, 1923) observed that the most characteristic mental manifestation of substan- tial war injury to the frontal lobes was a profound difficulty in forming and executing plans of goal-directed action. That symptom has since become pathognomonic of exten- sive frontal injury (Morris & Ward, 2005; Grafman, Vance, Weingartner, Salazar, & Amin, 1986; Luria, 1966, 1970; Goldstein, 1942; Kleist, 1934); it does not occur after any other form of extensive cortical lesion. Furthermore, it is demonstrably unrelated to depression or apathy, which also often results from some frontal lesions. In addition to the planning deficit, psychological and clinical reviews of frontal-lobe lesions often mention other manifestations of failed anticipation of future action and its consequences. Expectancy, prospective attention, creative intelligence, error prediction, and motor set are common casualties of frontal disease or trauma (reviewed in Fuster, 2008). From the diverse signs of its failure, the basic pro- spective functions of pFC can be inferred, including plan- ning, attentional set, working memory, decision-making, and error monitoring. The purpose of this review is to sum- marize the evidence that the prospective pFC functions are based on a common structural substrate, the cognit, and a common dynamic substrate, the perception–action (PA) cycle. Because it can be easily time-bracketed, working mem- ory is the frontal function with the clearest operational definition. We have written about it in the past from the perspective of the same network paradigm that we use here (Fuster & Bressler, 2012; Fuster, 2009). How- ever, the prospective, predictive aspect of working mem- ory, which Baddeley (1983) included in its definition, has been largely neglected. This review is an attempt to rem- edy that neglect and, furthermore, to relate two central concepts, the cognit and the PA cycle, to other prospec- tive prefrontal functions. The overall aim is to contribute understanding to the predictive role of pFC in the tem- poral organization of novel behavior. Because of the centrality of those two concepts, the cognit and the PA cycle, we briefly reiterate their previ- ously published descriptions. In a new context presented here, these descriptions confer generality to the princi- ples we are trying to establish about the predictive role 1 University of California, Los Angeles, 2 Florida Atlantic University © 2015 Massachusetts Institute of Technology Journal of Cognitive Neuroscience 27:4, pp. 639–654 doi:10.1162/jocn_a_00746