Humans have the capacity to form new memories of events that are, at times, highly similar to events experienced in the past, as well as the capacity to integrate and associate new information within existing knowledge structures. The former process relies on mnemonic discrimination and is believed to depend on hippocampal pattern separation, whereas the latter is believed to depend on generalization signals and conceptual categorization supported by the neocortex. Here, we examine whether and how the ventromedial prefrontal cortex (vMPFC) supports discrimination and generalization on a widely used task that was primarily designed to tax hippocampal processes. Ten individuals with lesions to the vMPFC and 46 neurotypical control participants were administered an adapted version of the mnemonic similarity task [Stark, S. M., Yassa, M. A., Lacy, J. W., & Stark, C. E. L. A task to assess behavioral pattern separation (BPS) in humans: Data from healthy aging and mild cognitive impairment. Neuropsychologia , 51 , 2442–2449, 2013], which assesses the ability to distinguish previously learned images of everyday objects (targets) from unstudied, highly similar images (lures) and dissimilar images (foils). Relative to controls, vMPFC-lesioned individuals showed intact discrimination of lures from targets but a propensity to mistake studied targets and similar lures for dissimilar foils. This pattern was accompanied by inflated confidence despite low accuracy when responding to similar lures. These findings demonstrate a more general role of the vMPFC in memory retrieval, rather than a specific role in supporting pattern separation.

If the tendency to discount rewards reflects individuals' general level of impulsiveness, then the discounting of delayed and probabilistic rewards should be negatively correlated: The less a person is able to wait for delayed rewards, the more they should take chances on receiving probabilistic rewards. It has been suggested that damage to the ventromedial prefrontal cortex (vmPFC) increases individuals' impulsiveness, but both intertemporal choice and risky choice have only recently been assayed in the same patients with vmPFC damage. Here, we assess both delay and probability discounting in individuals with vmPFC damage ( n = 8) or with medial temporal lobe (MTL) damage ( n = 10), and in age- and education-matched controls ( n = 30). On average, MTL-lesioned individuals discounted delayed rewards at normal rates but discounted probabilistic rewards more shallowly than controls. In contrast, vmPFC-lesioned individuals discounted delayed rewards more steeply but probabilistic rewards more shallowly than controls. These results suggest that vmPFC lesions affect the weighting of reward amount relative to delay and certainty in opposite ways. Moreover, whereas MTL-lesioned individuals and controls showed typical, nonsignificant correlations between the discounting of delayed and probabilistic rewards, vmPFC-lesioned individuals showed a significant negative correlation, as would be expected if vmPFC damage increases impulsiveness more in some patients than in others. Although these results are consistent with the hypothesis that vmPFC plays a role in impulsiveness, it is unclear how they could be explained by a single mechanism governing valuation of both delayed and probabilistic rewards.

The specific role of different parietal regions to episodic retrieval is a topic of intense debate. According to the Attention to Memory (AtoM) model, dorsal parietal cortex (DPC) mediates top–down attention processes guided by retrieval goals, whereas ventral parietal cortex (VPC) mediates bottom–up attention processes captured by the retrieval output or the retrieval cue. This model also hypothesizes that the attentional functions of DPC and VPC are similar for memory and perception. To investigate this last hypothesis, we scanned participants with event-related fMRI whereas they performed memory and perception tasks, each comprising an orienting phase (top–down attention) and a detection phase (bottom–up attention). The study yielded two main findings. First, consistent with the AtoM model, orienting-related activity for memory and perception overlapped in DPC, whereas detection-related activity for memory and perception overlapped in VPC. The DPC overlap was greater in the left intraparietal sulcus, and the VPC overlap in the left TPJ. Around overlapping areas, there were differences in the spatial distribution of memory and perception activations, which were consistent with trends reported in the literature. Second, both DPC and VPC showed stronger connectivity with medial-temporal lobe during the memory task and with visual cortex during the perception task. These findings suggest that, during memory tasks, some parietal regions mediate similar attentional control processes to those involved in perception tasks (orienting in DPC vs. detection in VPC), although on different types of information (mnemonic vs. sensory).

The contribution of the medial prefrontal cortex, particularly the anterior cingulate cortex (ACC), to cognitive control remains controversial. Here, we examined whether the rostral ACC is necessary for reactive adjustments in cognitive control following the occurrence of response conflict [Botvinick, M. M., Braver, T. S., Barch, D. M., Carter, C. S., & Cohen, J. D. Conflict monitoring and cognitive control. Psychological Review, 108 , 624–652, 2001]. To this end, we assessed 8 patients with focal lesions involving the rostral sector of the ACC (rACC patients), 6 patients with lesions outside the frontal cortex (non-FC patients), and 11 healthy subjects on a variant of the Simon task in which levels of conflict were manipulated on a trial-by-trial basis. More specifically, we compared Simon effects (i.e., the difference in performance between congruent and incongruent trials) on trials that were preceded by high-conflict (i.e., incongruent) trials with those on trials that were preceded by low-conflict (i.e., congruent) trials. Normal controls and non-FC patients showed a reduction of the Simon effect when the preceding trial was incongruent, suggestive of an increase in cognitive control in response to the occurrence of response conflict. In contrast, rACC patients attained comparable Simon effects following congruent and incongruent events, indicating a failure to modulate their performance depending on the conflict level generated by the preceding trial. Furthermore, damage to the rostral ACC impaired the posterror slowing, a further behavioral phenomenon indicating reactive adjustments in cognitive control. These results provide insights into the functional organization of the medial prefrontal cortex in humans and its role in the dynamic regulation of cognitive control.