The dorsomedial prefrontal cortex/dorsal anterior cingulate cortex (dmPFC/dACC) is a brain area subject to many theories and debates over its function(s). Even its precise anatomical borders are subject to much controversy. In the past decades, the dmPFC/dACC has been associated with more than 15 different cognitive processes, which sometimes appear quite unrelated (e.g. body perception, cognitive conflict). As a result, understanding what the dmPFC/dACC does has become a real challenge for many neuroscientists. Several theories of this brain area's function(s) have been developed, leading to successive and competitive publications bearing different models, which sometimes contradict each other. During the last two decades, the lively scientific exchanges around the dmPFC/dACC have promoted fruitful research in cognitive neuroscience. In this review, we provide an overview of the anatomy of the dmPFC/dACC, summarize the state of the art of functions that have been associated with this brain area and present the main theories aiming at explaining the dmPFC/dACC function(s). We explore the commonalities and the arguments between the different theories. Finally, we explain what can be learned from these debates for future investigations of the dmPFC/dACC and other brain regions' functions.

The ventromedial prefrontal cortex (vmPFC), which comprises several distinct cytoarchitectonic areas, is a key brain region supporting decision-making processes, and it has been shown to be one of the main hubs of the Default Mode Network, a network classically activated during resting state. We here examined the interindividual variability in the vmPFC sulcal morphology in 57 humans (37 females) and demonstrated that the presence/absence of the inferior rostral sulcus and the subgenual intralimbic sulcus influences significantly the sulcal organization of this region. Furthermore, the sulcal organization influences the location of the vmPFC peak of the Default Mode Network, demonstrating that the location of functional activity can be affected by local sulcal patterns. These results are critical for the investigation of the function of the vmPFC and show that taking into account the sulcal variability might be essential to guide the interpretation of neuroimaging studies.SIGNIFICANCE STATEMENTThe ventromedial prefrontal cortex (vmPFC) is one of the main hubs of the Default Mode Network and plays a central role in value coding and decision-making. The present study provides a complete description of the interindividual variability of anatomical morphology of this large portion of prefrontal cortex and its relation to functional organization. We have shown that two supplementary medial sulci predominantly determine the organization of the vmPFC, which in turn affects the location of the functional peak of activity in this region. Those results show that taking into account the variability in sulcal patterns might be essential to guide the interpretation of neuroimaging studies of the human brain and of the vmPFC in particular.

Understanding how option values are compared when making a choice is a key objective for decision neuroscience. In natural situations, agents may have a priori on their preferences that create default policies and shape the neural comparison process. We asked participants to make choices between items belonging to different categories (e.g., jazz vs. rock music). Behavioral data confirmed that the items taken from the preferred category were chosen more often and more rapidly, which qualified them as default options. FMRI data showed that baseline activity in classical brain valuation regions, such as the ventromedial Prefrontal Cortex (vmPFC), reflected the strength of prior preferences. In addition, evoked activity in the same regions scaled with the default option value, irrespective of the eventual choice. We therefore suggest that in the brain valuation system, choices are framed as comparisons between default and alternative options, which might save some resource but induce a decision bias.

Whether maximizing rewards and minimizing punishments rely on distinct brain systems remains debated, given inconsistent results coming from human neuroimaging and animal electrophysiology studies. Bridging the gap across techniques, we recorded intracerebral activity from twenty participants while they performed an instrumental learning task. We found that both reward and punishment prediction errors (PE), estimated from computational modeling of choice behavior, correlate positively with broadband gamma activity (BGA) in several brain regions. In all cases, BGA scaled positively with the outcome (reward or punishment versus nothing) and negatively with the expectation (predictability of reward or punishment). However, reward PE were better signaled in some regions (such as the ventromedial prefrontal and lateral orbitofrontal cortex), and punishment PE in other regions (such as the anterior insula and dorsolateral prefrontal cortex). These regions might therefore belong to brain systems that differentially contribute to the repetition of rewarded choices and the avoidance of punished choices.

Significance: Lateralization of functions in the brain has been demonstrated in many different cognitive processes. It is supposed to increase processing abilities by reducing bilateral redundancy. Yet lateralization of reward processing, despite extremely common asymmetrical findings, has received little attention. Our neuroimaging study shows a functional lateralization of the response to reward in the lateral part of the orbitofrontal cortex (OFC), together with an asymmetric functional connectivity pattern. This particular feature was identified not only in humans but also in nonhuman primates. Our findings challenge the classical view of the OFC as a symmetrical brain region. They are urging the need for considering the specific contribution of the left and right OFC when investigating reward-related signals.