Ventromedial Prefrontal Cortex Does Not Play a Selective Role in Pattern Separation.

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.

Taking time to compose thoughts with prefrontal schemata.

Under what conditions can prefrontal cortex direct the composition of brain states, to generate coherent streams of thoughts? Using a simplified Potts model of cortical dynamics, crudely differentiated into two halves, we show that once activity levels are regulated, so as to disambiguate a single temporal sequence, whether the contents of the sequence are mainly determined by the frontal or by the posterior half, or by neither, depends on statistical parameters that describe its microcircuits. The frontal cortex tends to lead if it has more local attractors, longer lasting and stronger ones, in order of increasing importance. Its guidance is particularly effective to the extent that posterior cortices do not tend to transition from state to state on their own. The result may be related to prefrontal cortex enforcing its temporally-oriented schemata driving coherent sequences of brain states, unlike the atemporal "context" contributed by the hippocampus. Modelling a mild prefrontal (vs. posterior) lesion offers an account of mind-wandering and event construction deficits observed in prefrontal patients.

Computational constraints on the associative recall of spatial scenes.

We consider a model of associative storage and retrieval of compositional memories in an extended cortical network. Our model network is comprised of Potts units, which represent patches of cortex, interacting through long-range connections. The critical assumption is that a memory, for example of a spatial view, is composed of a limited number of items, each of which has a pre-established representation: storing a new memory only involves acquiring the connections, if novel, among the participating items. The model is shown to have a much lower storage capacity than when it stores simple unitary representations. It is also shown that an input from the hippocampus facilitates associative retrieval. When it is absent, it is advantageous to cue rare rather than frequent items. The implications of these results for emerging trends in empirical research are discussed.

Retrograde amnesia abolishes the self-reference effect in anterograde memory.

Is retrograde amnesia associated with an ability to know who we are and imagine what we will be like in the future? To answer this question, we had S.G., a patient with focal retrograde amnesia following hypoxia, two brain-damaged (control) patients with no retrograde memory deficits, and healthy controls judge whether each of a series of trait adjectives was descriptive of their present self, future self, another person, and that person in the future, and later recognize studied traits among distractors. Healthy controls and control patients were more accurate in recognizing self-related compared to other-related traits, a phenomenon known as the self-reference effect (SRE). This held for both present and future self-views. By contrast, no evidence of (present or future) SRE was observed in SG, who concomitantly showed reduced certainty about his personality traits. These findings indicate that retrograde amnesia can weaken the self-schema and preclude its instantiation during self-related processing.

Déjà vu: A botched memory operation, illegitimate to start with.

Rather than a natural product, a computational analysis leads us to characterize déjà vu as a failure of memory retrieval, linked to the activation in neocortex of familiar items from a compositional memory in the absence of hippocampal input, and to a misappropriation by the self of what is of others.

Does Ventromedial Prefrontal Cortex Damage Really Increase Impulsiveness? Delay and Probability Discounting in Patients with Focal Lesions.

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.

Lesion network mapping demonstrates that mind-wandering is associated with the default mode network.

Functional neuroimaging research has consistently associated brain structures within the default mode network (DMN) and frontoparietal network (FPN) with mind-wandering. Targeted lesion research has documented impairments in mind-wandering after damage to the medial prefrontal cortex (mPFC) and hippocampal regions associated with the DMN. However, no lesion studies to date have applied lesion network mapping to identify common networks associated with deficits in mind-wandering. In lesion network mapping, resting-state functional connectivity data from healthy participants are used to infer which brain regions are functionally connected to each lesion location from a sample with brain injury. In the current study, we conducted a lesion network mapping analysis to test the hypothesis that lesions affecting the DMN and FPN would be associated with diminished mind-wandering. We assessed mind-wandering frequency on the Imaginal Processes Inventory (IPI) in participants with brain injury (n = 29) and healthy comparison participants without brain injury (n = 19). Lesion network mapping analyses showed the strongest association of reduced mind-wandering with the left inferior parietal lobule within the DMN. In addition, traditional lesion symptom mapping results revealed that reduced mind-wandering was associated with lesions of the dorsal, ventral, and anterior sectors of mPFC, parietal lobule, and inferior frontal gyrus in the DMN (p < 0.05 uncorrected). These findings provide novel lesion support for the role of the DMN in mind-wandering and contribute to a burgeoning literature on the neural correlates of spontaneous cognition.

Differential impact of ventromedial prefrontal cortex damage on "hot" and "cold" decisions under risk.

The ventromedial prefrontal cortex (vmPFC) is known to play a key role in reward processing and decision making. However, its relative contribution to affect-rich ("hot") and affect-poor ("cold") decisions is not fully understood. Damage to vmPFC is associated with impaired performance on laboratory tasks of decision making under ambiguity and risk. In the current study, we tested the hypothesis that vmPFC is critical for adaptive risk taking under "hot" conditions specifically. Participants included patients with focal lesions in vmPFC, patient controls with damage in regions not including vmPFC, and healthy controls. They completed hot and cold versions of a dynamic risk-taking task, the Columbia Card Task (CCT). Relative to healthy controls and patient controls, vmPFC patients showed a strong overall increase in risk taking in the hot version of the CCT, despite preserved sensitivity to trial-level variation in risk. In the cold version, overall risk taking was similar among all three groups, even though vmPFC patients showed reduced sensitivity to trial-level variation in risk. Sensitivity to gain and loss magnitudes did not differ significantly among the groups, in either the hot or the cold CCT. These findings lend novel support to the hypothesis that the vmPFC is critical for adaptive decision making under affect-rich conditions.

Age-Related Effects on Future Mental Time Travel.

Mental time travel (MTT), the ability to travel mentally back and forward in time in order to reexperience past events and preexperience future events, is crucial in human cognition. As we move along life, MTT may be changed accordingly. However, the relation between re- and preexperiencing along the lifespan is still not clear. Here, young and older adults underwent a psychophysical paradigm assessing two different components of MTT: self-projection, which is the ability to project the self towards a past or a future location of the mental time line, and self-reference, which is the ability to determine whether events are located in the past or future in reference to that given self-location. Aged individuals performed worse in both self-projection to the future and self-reference to future events compared to young individuals. In addition, aging decreased older adults' preference for personal compared to nonpersonal events. These results demonstrate the impact of MTT and self-processing on subjective time processing in healthy aging. Changes in memory functions in aged people may therefore be related not only to memory per se, but also to the relations of memory and self.

The parietal cortex and episodic memory: an attentional account.

The contribution of the parietal cortex to episodic memory is a fascinating scientific puzzle. On the one hand, parietal lesions do not normally yield severe episodic-memory deficits; on the other hand, parietal activations are seen frequently in functional-neuroimaging studies of episodic memory. A review of these two categories of evidence suggests that the answer to the puzzle requires us to distinguish between the contributions of dorsal and ventral parietal regions and between the influence of top-down and bottom-up attention on memory.

Who am I really? The ephemerality of the self-schema following vmPFC damage.

We studied the role of the ventromedial prefrontal cortex (vmPFC) in supporting the self-schema, by asking vmPFC patients, along with healthy and brain-damaged controls, to judge the degree to which they (or another person) were likely to engage in a series of activities, and how confident they were in their responses. Critically, participants provided their judgments on two separate occasions, a week apart. Our underlying assumption was that a strong self-schema would lead to confident and stable self-related judgments. We observed that control groups exhibited higher across-session consistency for self-related compared to other-related judgments, while this self-advantage was absent in vmPFC patients. In addition, regression analyses showed that in control groups the level of confidence associated with a specific (self- or other-related) judgment predicted the stability of that judgment across sessions. In contrast, vmPFC patients' confidence and rating consistency were aligned only for other-related judgments. By contrast, self-related judgments changed across sessions regardless of the confidence level with which they were initially endorsed. These findings indicate that the vmPFC is crucial to maintaining the self-schema and supporting the reliable retrieval of self-related information.

The role of posterior parietal cortex and medial prefrontal cortex in distraction and mind-wandering.

Distraction reflects a drift of attention away from the task at hand towards task-irrelevant external or internal information (mind-wandering). The right posterior parietal cortex (PPC) and the medial prefrontal cortex (mPFC) are known to mediate attention to external information and mind-wandering, respectively, but it is not clear whether they support each process selectively or rather they play similar roles in supporting both. In this study, participants performed a visual search task including salient color singleton distractors before and after receiving cathodal (inhibitory) transcranial direct current stimulation (tDCS) to the right PPC, the mPFC, or sham tDCS. Thought probes assessed the intensity and contents of mind-wandering during visual search. The results show that tDCS to the right PPC but not mPFC reduced the attentional capture by the singleton distractor during visual search. tDCS to both mPFC and PPC reduced mind-wandering, but only tDCS to the mPFC specifically reduced future-oriented mind-wandering. These results suggest that the right PPC and mPFC play a different role in directing attention towards task-irrelevant information. The PPC is involved in both external and internal distraction, possibly by mediating the disengagement of attention from the current task and its reorienting to salient information, be this a percept or a mental content (mind-wandering). By contrast, the mPFC uniquely supports mind-wandering, possibly by mediating the endogenous generation of future-oriented thoughts capable to draw attention inward, away from ongoing activities.

Time bisection and reproduction: Evidence for a slowdown of the internal clock in right brain damaged patients.

Previous studies show that the right hemisphere is involved in time processing, and that damage to the right hemisphere is associated with a tendency to perceive time intervals as shorter than they are, and to reproduce time intervals as longer than they are. Whether time processing deficits following right hemisphere damage are related and what is their neurocognitive basis is unclear. In this study, right brain damaged (RBD) patients, left brain damaged (LBD) patients, and healthy controls underwent a time bisection task and a time reproduction task involving time intervals varying between each other by milliseconds (short durations) or seconds (long durations). The results show that in the time bisection task RBD patients underestimated time intervals compared to LBD patients and healthy controls, while they reproduced time intervals as longer than they are. Time underestimation and over-reproduction in RBD patients applied to short but not long time intervals, and were correlated. Voxel-based lesion-symptom mapping (VLSM) showed that time underestimation was associated with lesions to a right cortico-subcortical network involving the insula and inferior frontal gyrus. A small portion of this network was also associated with time over-reproduction. Our findings are consistent with a slowdown of an 'internal clock' timing mechanism following right brain damage, which likely underlies both the underestimation and the over-reproduction of time intervals, and their (overlapping) neural bases.

Top-down and bottom-up attention-to-memory: mapping functional connectivity in two distinct networks that underlie cued and uncued recognition memory.

The objective of this study was to examine the functional connectivity of brain regions active during cued and uncued recognition memory to test the idea that distinct networks would underlie these memory processes, as predicted by the attention-to-memory (AtoM) hypothesis. The AtoM hypothesis suggests that dorsal parietal cortex (DPC) allocates effortful top-down attention to memory retrieval during cued retrieval, whereas ventral parietal cortex (VPC) mediates spontaneous bottom-up capture of attention by memory during uncued retrieval. To identify networks associated with these two processes, we conducted a functional connectivity analysis of a left DPC and a left VPC region, both identified by a previous analysis of task-related regional activations. We hypothesized that the two parietal regions would be functionally connected with distinct neural networks, reflecting their engagement in the differential mnemonic processes. We found two spatially dissociated networks that overlapped only in the precuneus. During cued trials, DPC was functionally connected with dorsal attention areas, including the superior parietal lobules, right precuneus, and premotor cortex, as well as relevant memory areas, such as the left hippocampus and the middle frontal gyri. During uncued trials, VPC was functionally connected with ventral attention areas, including the supramarginal gyrus, cuneus, and right fusiform gyrus, as well as the parahippocampal gyrus. In addition, activity in the DPC network was associated with faster response times for cued retrieval. This is the first study to show a dissociation of the functional connectivity of posterior parietal regions during episodic memory retrieval, characterized by a top-down AtoM network involving DPC and a bottom-up AtoM network involving VPC.

It is the outcome that counts! Damage to the ventromedial prefrontal cortex disrupts the integration of outcome and belief information for moral judgment.

Moral judgment involves considering not only the outcome of an action but also the intention with which it was pursued. Previous functional magnetic resonance imaging (fMRI) research has shown that integrating outcome and belief information for moral judgment relies on a brain network including temporo-parietal, precuneus, and medial prefrontal regions. Here, we investigated whether the ventromedial prefrontal cortex (vmPFC) plays a crucial role in this process. Patients with lesions in vmPFC (vmPFC patients), and brain-damaged and healthy controls considered scenarios in which the protagonist caused intentional harm (negative-outcome, negative-belief), accidental harm (negative-outcome, neutral-belief), attempted harm (neutral-outcome, negative-belief), or no harm (neutral-outcome, neutral-belief), and rated the moral permissibility of the protagonists' behavior. All groups responded similarly to scenarios involving intentional harm and no harm. vmPFC patients, however, judged attempted harm as more permissible, and accidental harm as less permissible, than the control groups. For vmPFC patients, outcome information, rather than belief information, shaped moral judgment. The results indicate that vmPFC is necessary for integrating outcome and belief information during moral reasoning. During moral judgment vmPFC may mediate intentions' understanding, and overriding of prepotent responses to salient outcomes.

Myopic discounting of future rewards after medial orbitofrontal damage in humans.

Choices are often intertemporal, requiring tradeoff of short-term and long-term outcomes. In such contexts, humans may prefer small rewards delivered immediately to larger rewards delivered after a delay, reflecting temporal discounting (TD) of delayed outcomes. The medial orbitofrontal cortex (mOFC) is consistently activated during intertemporal choice, yet its role remains unclear. Here, patients with lesions in the mOFC (mOFC patients), control patients with lesions outside the frontal lobe, and healthy individuals chose hypothetically between small-immediate and larger-delayed rewards. The type of reward varied across three TD tasks, including both primary (food) and secondary (money and discount vouchers) rewards. We found that damage to mOFC increased significantly the preference for small-immediate over larger-delayed rewards, resulting in steeper TD of future rewards in mOFC patients compared with the control groups. This held for both primary and secondary rewards. All participants, including mOFC patients, were more willing to wait for delayed money and discount vouchers than for delayed food, suggesting that mOFC patients' (impatient) choices were not due merely to poor motor impulse control or consideration of the goods at stake. These findings provide the first evidence in humans that mOFC is necessary for valuation and preference of delayed rewards for intertemporal choice.

Top-down and bottom-up attention to memory are dissociated in posterior parietal cortex: neuroimagingand and neuropsychological evidence.

Posterior parietal cortex is active during episodic memory retrieval, yet its role remains unclear. According to a recent proposal, dorsal parietal cortex (DPC) allocates top-down attention to memory retrieval, whereas ventral parietal cortex (VPC) mediates the bottom-up attentional capture by retrieved contents, i.e., the Attention-to-Memory (AtoM) hypothesis. Here, for the first time, functional magnetic resonance imaging (fMRI) and lesion techniques were combined in a single study to test the role of parietal cortex in episodic retrieval. Participants studied word pairs and then detected studied (target) words among new words. In some conditions, a studied word cued the upcoming target word, facilitating recognition performance. In line with the AtoM hypothesis, left DPC was engaged when participants searched for/anticipated memory targets upon presentation of relevant memory cues and predicted the ensuing behavioral advantage. In contrast, left VPC predicted efficacy and speed of target detection on noncued trials and was largest for memory targets that were invalidly cued. Consistent with fMRI evidence, patients with lesions in DPC did not benefit from memory cueing, whereas patients with lesions in VPC had problems recognizing unexpected memory targets. These results support the AtoM hypothesis that DPC and VPC mediate top-down and bottom-up attention to memory retrieval, respectively.

Overlapping parietal activity in memory and perception: evidence for the attention to memory model.

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 neurobiology of intertemporal choice: insight from imaging and lesion studies.

People are frequently faced with intertemporal choices, i.e., choices differing in the timing of their consequences, preferring smaller rewards available immediately over larger rewards delivered after a delay. The inability to forgo sooner gratification to favor delayed reward (e.g., impulsivity) has been related to several pathological conditions characterized by poor self-control, including drug addiction and obesity. Comparative and functional human studies have implicated a network of brain areas involved in intertemporal choice, including the medial portion of the orbitofrontal cortex (mOFC). Moreover, damage to this cortical area increases preference for immediate gratification in intertemporal decisions. Here, we review recent neuroscientific studies concerning intertemporal choice, suggesting that the mOFC contributes to preference for delayed rewards, either by computing the value of future outcomes (i.e., valuation), or by enabling people to imagine and represent future rewards and their consequences (e.g., prospection).

Development of subjective recollection: understanding of and introspection on memory States.

The development of subjective recollection was investigated in participants aged 6-18 years. In Experiment 1 (N = 90), age-related improvements were found in understanding of the subjective experience of recollection, although robust levels of understanding were observed even in the youngest group. In Experiment 2 (N = 100), age-related differences were found in subjective recollection during a memory task, suggesting development not only in the ability to reflect on memory states, but also in the informational basis of subjective recollection. Lower understanding of memory states was associated with increased propensity to claim recollection. These results indicate that subjective recollection develops considerably during childhood and suggest that the development of metamemory supports this capacity.