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.

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.

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.

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.

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.

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.

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.

Navigating through the ebbs and flows of language.

Is progress in understanding the neural basis for spatial navigation relevant to the human language faculty? Not so much at the shortest scale, where movement is continuous, a recent study in the space of vowels suggests. At a much larger scale, however, that of the verbalization of run-away thoughts, a rich phenomenology appears to involve critical contributions by some of the brain structures also involved in spatial cognition. Their interactions may have to be approached with models operating at an integrated cortical level and allowing for the compositionality of multiple local attractor states. A useful window on the latching dynamics enabled by cortico-cortical interactions may be offered by altered states of consciousness. As an example, psychedelic states have been reported to alter the graph properties of functional connectivity in the cortex so as to facilitate wide-ranging trips.

The role of ventromedial prefrontal cortex in reward valuation and future thinking during intertemporal choice.

Intertemporal choices require trade-offs between short-term and long-term outcomes. Ventromedial prefrontal cortex (vmPFC) damage causes steep discounting of future rewards (delay discounting [DD]) and impoverished episodic future thinking (EFT). The role of vmPFC in reward valuation, EFT, and their interaction during intertemporal choice is still unclear. Here, 12 patients with lesions to vmPFC and 41 healthy controls chose between smaller-immediate and larger-delayed hypothetical monetary rewards while we manipulated reward magnitude and the availability of EFT cues. In the EFT condition, participants imagined personal events to occur at the delays associated with the larger-delayed rewards. We found that DD was steeper in vmPFC patients compared to controls, and not modulated by reward magnitude. However, EFT cues downregulated DD in vmPFC patients as well as controls. These findings indicate that vmPFC integrity is critical for the valuation of (future) rewards, but not to instill EFT in intertemporal choice.

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.

Present and future self in memory: the role of vmPFC in the self-reference effect.

Self-related information is remembered better than other-related information (self-reference effect; SRE), a phenomenon that has been convincingly linked to the medial prefrontal cortex. It is not clear whether information related to our future self would also have a privileged status in memory, as medial prefrontal cortex (mPFC) regions respond less to the future than to the present self, as if it were an 'other'. Here we ask whether the integrity of the ventral mPFC (vmPFC) is necessary for the emergence of the present and future SRE, if any. vmPFC patients and brain-damaged and healthy controls judged 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 recognized studied traits among distractors. Information relevant to the present (vs future) was generally recognized better, across groups. However, whereas healthy and brain-damaged controls exhibited strong present and future SREs, these were absent in vmPFC patients, who concomitantly showed reduced certainty about their own present and anticipated traits compared to the control groups. These findings indicate that vmPFC is necessary to impart a special mnemonic status to self-related information, including our envisioned future self, possibly by instantiating the self-schema.

An asymmetry in past and future mental time travel following vmPFC damage.

The role of ventromedial prefrontal cortex (vmPFC) in mental time travel toward the past and the future is debated. Here, patients with focal lesions to the vmPFC and brain-damaged and healthy controls mentally projected themselves to a past, present or future moment of subjective time (self-projection) and classified a series of events as past or future relative to the adopted temporal self-location (self-reference). We found that vmPFC patients were selectively impaired in projecting themselves to the future and in recognizing relative-future events. These findings indicate that vmPFC damage hinders the mental processing of and movement toward future events, pointing to a prominent, multifaceted role of vmPFC in future-oriented mental time travel.

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.

Functional Interplay Between Posterior Parietal Cortex and Hippocampus During Detection of Memory Targets and Non-targets.

Posterior parietal cortex is frequently activated during episodic memory retrieval but its role during retrieval and its interactions with the hippocampus are not yet clear. In this fMRI study, we investigated the neural bases of recognition memory when study repetitions and retrieval goals were manipulated. During encoding participants studied words either once or three times, and during retrieval they were rewarded more to detect either studied words or new words. We found that (1) dorsal parietal cortex (DPC) was more engaged during detection of items studied once compared to three times, whereas regions in the ventral parietal cortex (VPC) responded more to items studied multiple times; (2) DPC, within a network of brain regions functionally connected to the anterior hippocampus, responded more to items consistent with retrieval goals (associated with high reward); (3) VPC, within a network of brain regions functionally connected to the posterior hippocampus, responded more to items not aligned with retrieval goals (i.e., unexpected). These findings support the hypothesis that DPC and VPC regions contribute differentially to top-down vs. bottom-up attention to memory. Moreover, they reveal a dissociation in the functional profile of the anterior and posterior hippocampi.

The space for memory in posterior parietal cortex: Re-analyses of bottom-up attention data.

The ventral (VPC) and dorsal sectors of the posterior parietal cortex are long known to mediate bottom-up and top-down attention to the external space. Because these regions also are implicated in retrieval of episodic memories, we proposed they also mediate attention to the internal (memory) space. One objection to this Attention to Memory hypothesis is that parietal regions involved in directing attention to percepts and memory are spatially adjacent but not overlapping, suggesting that different neural mechanisms are involved in each. This misalignment is most pronounced in VPC. Here, we re-examine fMRI data, and show that (1) different VPC subregions are associated with different aspects of bottom-up attention to the external space, (2) only VPC subregions showing invalid cue (but not oddball) effects overlap with those associated with episodic memory retrieval, leading us to conclude that (3) the same regions that signal unexpected percepts also signal unexpected memories. These findings are consistent with the 'overarching view' of VPC as deploying bottom-up attention during both perception and episodic memory retrieval, and suggest that the degree of anatomical convergence across the two domains depends on the correspondence between the specific bottom-up attention demands of perceptual and memory tasks.

Scene processing following damage to the ventromedial prefrontal cortex.

It has been suggested that the mental construction of scene imagery is a core process underpinning functions such as autobiographical memory, future thinking and spatial navigation. Damage to the ventromedial prefrontal cortex in humans can cause deficits in all of these cognitive domains. Moreover, it has also been reported that patients with ventromedial prefrontal cortex lesions are impaired at imagining fictitious scenes, although they seem able to describe specific scenes from autobiographical events. In general, not much is known about how ventromedial prefrontal cortex patients process scenes. Here, we deployed a recently-developed task to provide insights into this issue, which involved detecting either semantic (e.g. an elephant with butterflies for ears) or constructive (e.g. an endless staircase) violations in scene images. Identifying constructive violations typically provokes the formation of internal scene models in healthy control participants. We tested patients with bilateral ventromedial prefrontal cortex damage, brain-damaged control patients and healthy control participants. We found no evidence for statistically significant differences between the groups in detecting either type of violation. These results suggest that an intact ventromedial prefrontal cortex is not necessary for some aspects of scene processing, with implications for understanding its role in functions such as autobiographical memory and future thinking.

Intentionality attribution and emotion: The Knobe Effect in alexithymia.

The capacity to distinguish between intentional and unintentional actions is a crucial aspect of moral competence. Therefore, the processes shaping intentionality attribution, as well as their dysfunction, are object of intense inquiry. The 'Knobe effect' refers to the intriguing finding that people are more likely to judge as intentional actions leading to negative as opposed to positive side effects, which has been attributed to the emotional response elicited by negative (vs. positive) outcomes. Whether and how emotion drives the Knobe effect, however, is currently debated. Here, individuals with low (LA) and high (HA) levels of alexithymia, a personality trait characterized by difficulties in emotional processing, judged the intentionality of actions with side effects that varied in valence (positive/negative) and salience (low/high), while their subjective emotional response and skin conductance level were assessed. LA individuals attributed more intentionality to actions leading to negative (vs. positive) side effects, and to high (vs. low) salience side effects, and this related to their subjective emotional response to negative side effects. In the context of a generally reduced physiological activation to emotional stimuli, HA (compared to LA) individuals attributed less intentionality to actions leading to negative side effects, especially those with low salience, showing a reduced Knobe effect, which was accompanied by a reduced subjective emotional response to negative side effects. These results confirm the crucial role of emotion on intentionality attribution. Moreover, they contribute to qualifying the emotional processing difficulties associated with alexithymia, and their impact on moral cognition.