Essential functions of primate frontopolar cortex in cognition

Brodmann’s area 10 is one of the largest cytoarchitecturally defined regions in the human cerebral cortex, occupying the most anterior part of the prefrontal cortex [frontopolar cortex (FPC)], and is believed to sit atop a prefrontal hierarchy. The crucial contributions that the FPC makes to cognition are unknown. Rodents do not possess such a FPC, but primates do, and we report here the behavioral effects of circumscribed FPC lesions in nonhuman primates. FPC lesions selectively impaired rapid one-trial learning about unfamiliar objects and unfamiliar objects-in-scenes, and also impaired rapid learning about novel abstract rules. Object recognition memory, shifting between established abstract behavioral rules, and the simultaneous application of two distinct rules were unaffected by the FPC lesion. The distinctive pattern of impaired and spared performance across these seven behavioral tasks reveals that the FPC mediates exploration and rapid learning about the relative value of novel behavioral options, and shows that the crucial contributions made by the FPC to cognition differ markedly from the contributions of other primate prefrontal regions.Granular prefrontal cortex (gPFC) is unique to anthropoid primates (1), and is believed to underlie the ability to construct novel, complex, structured sequences of intelligent, goal-directed behavior (2). Although the frontopolar cortex (FPC), the most rostral gPFC region, is particularly well developed in hominoids and in humans (3), it is also a substantial cortical structure in monkeys. In both macaques and humans, the lateral, medial, and ventral aspects of the FPC are typically occupied by “area 10” (4–9). FPC connections are also broadly similar across primate species (6, 10–13). The similarity in cytoarchitecture and connections is highly suggestive of some conservation of FPC function across primate species.Anatomical connections suggest that the FPC sits atop a gPFC hierarchy, yet we do not know what crucial contribution(s) the FPC makes to cognition or how this contribution(s) differs from other gPFC regions. FPC blood oxygen level-dependent activity has been correlated with a bafflingly diverse range of cognitive processes, including implementing task sets (14), multitasking (15), future thinking and prospective memory (16–18), deferring goals and cognitive “branching” (19), exploratory decision making (20), evaluating counterfactual choice (21), complex relational and abstract reasoning (22), integrating outcomes of multiple cognitive operations (23), coordinating internal and external influences on cognition (24), evaluating self-generated information (25), episodic memory retrieval and detailed recollection (26–28), and facing uncertainty or conflict (29–31), for example. Patients with FPC lesions behave inappropriately, particularly in uncertain contexts, and show deficiencies in prospective memory and planning (32–34), but their lesions are large and unselective, and their premorbid performance is unknown. Hence, no consensus has emerged from human neuroimaging and neuropsychology as to what the common underlying contribution(s) of the FPC to cognition might be (23, 35). Targeted electrophysiological recording and circumscribed lesion studies in animal models have had major influences on understanding the contributions to cognition of a broad range of other gPFC areas (2), but such is not the case for the FPC. To date, there are only two primary reports of targeted FPC recordings, (36, 37) and, despite imaging evidence showing FPC activation across a wide range of complex cognitive tasks, many of the patterns of neuronal activity associated with the flexible and complex goal-directed behavior that are usually observed in other gPFC areas (2) were not observed in the FPC (36, 37), suggesting the FPC’s role in these tasks might be different from the role of neighboring areas. Previous lesion studies confirm gPFC areas adjacent to the FPC are necessary for supporting efficient exploitation of current complex tasks/goals (38–44), but no study has yet investigated the effects of circumscribed FPC lesions to identify the FPC’s necessary contribution to cognition. Hence, we aimed to accomplish the following: (i) determine what basic elements of complex, rapidly flexible, goal-directed behavior were crucially dependent upon the FPC; (ii) ascertain whether and how the contribution of the FPC to cognition differs from the rest of gPFC; and (iii) provide an animal model of FPC function to help constrain and inspire hypotheses about the role of the FPC in humans, especially in view of its large volume.