Variability in the analysis of a single neuroimaging dataset by many teams.

Data analysis workflows in many scientific domains have become increasingly complex and flexible. Here we assess the effect of this flexibility on the results of functional magnetic resonance imaging by asking 70 independent teams to analyse the same dataset, testing the same 9 ex-ante hypotheses1. The flexibility of analytical approaches is exemplified by the fact that no two teams chose identical workflows to analyse the data. This flexibility resulted in sizeable variation in the results of hypothesis tests, even for teams whose statistical maps were highly correlated at intermediate stages of the analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Notably, a meta-analytical approach that aggregated information across teams yielded a significant consensus in activated regions. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset2-5. Our findings show that analytical flexibility can have substantial effects on scientific conclusions, and identify factors that may be related to variability in the analysis of functional magnetic resonance imaging. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for performing and reporting multiple analyses of the same data. Potential approaches that could be used to mitigate issues related to analytical variability are discussed.

A reward effect on memory retention, consolidation, and generalization?

Reward improves memory through both encoding and consolidation processes. In this preregistered study, we tested whether reward effects on memory generalize from high-rewarded items to low-rewarded but episodically related items. Fifty-nine human volunteers incidentally encoded associations between unique objects and repeated scenes. Some scenes typically yielded high reward, whereas others typically yielded low reward. Memory was tested immediately after encoding (n = 29) or the next day (n = 30). Overall, reward had only a limited influence on memory. It did not enhance consolidation and its effect did not generalize to episodically related stimuli. We thus contribute to understanding the boundary conditions of reward effects on memory.

Reducing future fears by suppressing the brain mechanisms underlying episodic simulation.

Imagining future events conveys adaptive benefits, yet recurrent simulations of feared situations may help to maintain anxiety. In two studies, we tested the hypothesis that people can attenuate future fears by suppressing anticipatory simulations of dreaded events. Participants repeatedly imagined upsetting episodes that they feared might happen to them and suppressed imaginings of other such events. Suppressing imagination engaged the right dorsolateral prefrontal cortex, which modulated activation in the hippocampus and in the ventromedial prefrontal cortex (vmPFC). Consistent with the role of the vmPFC in providing access to details that are typical for an event, stronger inhibition of this region was associated with greater forgetting of such details. Suppression further hindered participants' ability to later freely envision suppressed episodes. Critically, it also reduced feelings of apprehensiveness about the feared scenario, and individuals who were particularly successful at down-regulating fears were also less trait-anxious. Attenuating apprehensiveness by suppressing simulations of feared events may thus be an effective coping strategy, suggesting that a deficiency in this mechanism could contribute to the development of anxiety.

Increased hippocampus to ventromedial prefrontal connectivity during the construction of episodic future events.

Both the hippocampus and ventromedial prefrontal cortex (vmPFC) appear to be critical for episodic future simulation. Damage to either structure affects one's ability to remember the past and imagine the future, and both structures are commonly activated as part of a wider core network during future simulation. However, the precise role played by each of these structures and, indeed, the direction of information flow between them during episodic simulation, is still not well understood. In this study, we scanned participants using functional magnetic resonance imaging while they imagined future events in response to object cues. We then used dynamic causal modeling to examine effective connectivity between the left anterior hippocampus and vmPFC during the initial mental construction of the events. Our results show that while there is strong bidirectional intrinsic connectivity between these regions (i.e., irrespective of task conditions), only the hippocampus to vmPFC connection increases during the construction of episodic future events, suggesting that the hippocampus initiates event simulation in response to retrieval cues, driving activation in the vmPFC where episodic details may be further integrated.

An adaptive function of mental time travel: Motivating farsighted decisions.

The episodic memory system allows us to experience the emotions of past, counterfactual, and prospective events. We outline how this phenomenological experience can convey motivational incentives for farsighted decisions. In this way, we challenge important arguments for Mahr & Csibra's (M&C's) conclusion that future-oriented mental time travel is unlikely to be a central function of episodic memory.

Characterizing the role of the hippocampus during episodic simulation and encoding.

The hippocampus has been consistently associated with episodic simulation (i.e., the mental construction of a possible future episode). In a recent study, we identified an anterior-posterior temporal dissociation within the hippocampus during simulation. Specifically, transient simulation-related activity occurred in relatively posterior portions of the hippocampus and sustained activity occurred in anterior portions. In line with previous theoretical proposals of hippocampal function during simulation, the posterior hippocampal activity was interpreted as reflecting a transient retrieval process for the episodic details necessary to construct an episode. In contrast, the sustained anterior hippocampal activity was interpreted as reflecting the continual recruitment of encoding and/or relational processing associated with a simulation. In the present study, we provide a direct test of these interpretations by conducting a subsequent memory analysis of our previously published data to assess whether successful encoding during episodic simulation is associated with the anterior hippocampus. Analyses revealed a subsequent memory effect (i.e., later remembered > later forgotten simulations) in the anterior hippocampus. The subsequent memory effect was transient and not sustained. Taken together, the current findings provide further support for a component process model of hippocampal function during simulation. That is, unique regions of the hippocampus support dissociable processes during simulation, which include the transient retrieval of episodic information, the sustained binding of such information into a coherent episode, and the transient encoding of that episode for later retrieval.

Priming, not inhibition, of related concepts during future imagining.

Remembering the past and imagining the future both involve the retrieval of details stored in episodic memory and rely on the same core network of brain regions. Given these parallels, one might expect similar component processes to be involved in remembering and imagining. While a strong case can be made for the role of inhibition in memory retrieval, few studies have examined whether inhibition is also necessary for future imagining and results to-date have been mixed. In the current study, we test whether related concepts are inhibited during future imagining using a modified priming approach. Participants first generated a list of familiar places and for each place, the people they most strongly associate with it. A week later, participants imagined future events involving recombinations of people and places, immediately followed by a speeded response task in which participants made familiarity decisions about people's names. Across two experiments, our results suggest that related concepts are not inhibited during future imagining, but rather are automatically primed. These results fit with recent work showing that autobiographically significant concepts (e.g., friends' names) are more episodic than semantic in nature, automatically activating related details in memory and potentially fuelling the flexible simulation of future events.

Ventromedial prefrontal cortex supports affective future simulation by integrating distributed knowledge.

Although the future often seems intangible, we can make it more concrete by imagining prospective events. Here, using functional MRI, we demonstrate a mechanism by which the ventromedial prefrontal cortex supports such episodic simulations, and thereby contributes to affective foresight: This region supports processes that (i) integrate knowledge related to the elements that constitute an episode and (ii) represent the episode's emergent affective quality. The ventromedial prefrontal cortex achieves such integration via interactions with distributed cortical regions that process the individual elements. Its activation then signals the affective quality of the ensuing episode, which goes beyond the combined affective quality of its constituting elements. The integrative process further augments long-term retention of the episode, making it available at later time points. This mechanism thus renders the future tangible, providing a basis for farsighted behavior.

Reflections of Oneself: Neurocognitive Evidence for Dissociable Forms of Self-Referential Recollection.

Research links the medial prefrontal cortex (mPFC) with a number of social cognitive processes that involve reflecting on oneself and other people. Here, we investigated how mPFC might support the ability to recollect information about oneself and others relating to previous experiences. Participants judged whether they had previously related stimuli conceptually to themselves or someone else, or whether they or another agent had performed actions. We uncovered a functional distinction between dorsal and ventral mPFC subregions based on information retrieved from episodic long-term memory. The dorsal mPFC was generally activated when participants attempted to retrieve social information about themselves and others, regardless of whether this information concerned the conceptual or agentic self or other. In contrast, a role was discerned for ventral mPFC during conceptual but not agentic self-referential recollection, indicating specific involvement in retrieving memories related to self-concept rather than bodily self. A subsequent recognition test for new items that had been presented during the recollection task found that conceptual and agentic recollection attempts resulted in differential incidental encoding of new information. Thus, we reveal converging fMRI and behavioral evidence for distinct neurocognitive forms of self-referential recollection, highlighting that conceptual and bodily aspects of self-reflection can be dissociated.

Adaptive top-down suppression of hippocampal activity and the purging of intrusive memories from consciousness.

When reminded of unwanted memories, people often attempt to suppress these experiences from awareness. Prior work indicates that control processes mediated by the dorsolateral prefrontal cortex (DLPFC) modulate hippocampal activity during such retrieval suppression. It remains unknown whether this modulation plays a role in purging an intrusive memory from consciousness. Here, we combined fMRI and effective connectivity analyses with phenomenological reports to scrutinize a role for adaptive top-down suppression of hippocampal retrieval processes in terminating mnemonic awareness of intrusive memories. Participants either suppressed or recalled memories of pictures depicting faces or places. After each trial, they reported their success at regulating awareness of the memory. DLPFC activation was greatest when unwanted memories intruded into consciousness and needed to be purged, and this increased engagement predicted superior control of intrusive memories over time. However, hippocampal activity was decreased during the suppression of place memories only. Importantly, the inhibitory influence of the DLPFC on the hippocampus was linked to the ensuing reduction in intrusions of the suppressed memories. Individuals who exhibited negative top-down coupling during early suppression attempts experienced fewer involuntary memory intrusions later on. Over repeated suppressions, the DLPFC-hippocampus connectivity grew less negative with the degree that they no longer had to purge unwanted memories from awareness. These findings support a role of DLPFC in countermanding the unfolding recollection of an unwanted memory via the suppression of hippocampal processing, a mechanism that may contribute to adaptation in the aftermath of traumatic experiences.

Episodic future thinking and episodic counterfactual thinking: intersections between memory and decisions.

This article considers two recent lines of research concerned with the construction of imagined or simulated events that can provide insight into the relationship between memory and decision making. One line of research concerns episodic future thinking, which involves simulating episodes that might occur in one's personal future, and the other concerns episodic counterfactual thinking, which involves simulating episodes that could have happened in one's personal past. We first review neuroimaging studies that have examined the neural underpinnings of episodic future thinking and episodic counterfactual thinking. We argue that these studies have revealed that the two forms of episodic simulation engage a common core network including medial parietal, prefrontal, and temporal regions that also supports episodic memory. We also note that neuroimaging studies have documented neural differences between episodic future thinking and episodic counterfactual thinking, including differences in hippocampal responses. We next consider behavioral studies that have delineated both similarities and differences between the two kinds of episodic simulation. The evidence indicates that episodic future and counterfactual thinking are characterized by similarly reduced levels of specific detail compared with episodic memory, but that the effects of repeatedly imagining a possible experience have sharply contrasting effects on the perceived plausibility of those events during episodic future thinking versus episodic counterfactual thinking. Finally, we conclude by discussing the functional consequences of future and counterfactual simulations for decisions.

Rostral prefrontal cortex and the focus of attention in prospective memory.

Prospective memory (PM) denotes the function to realize intentions after a delay while being immersed in distracting ongoing (OG) activity. Here, we scrutinize the often-reported involvement of rostral prefrontal cortex (rPFC; approximating Brodmann area 10) in such situations: This region might mediate attention between external stimuli and the internally maintained intention, that is, between stimulus-oriented (SO) and stimulus-independent (SI) processing. Using functional magnetic resonance imaging (fMRI) we orthogonally crossed 1) PM versus OG activity only, with 2) SO versus SI attention. In support of the hypothesis, common regions of medial rPFC exhibited greater blood oxygen level-dependent (BOLD) signal for the contrasts of both OG task only versus PM and SO versus SI attending. However, activation related to the former contrast extended more superiorly, suggesting a functional gradient along a dorsal-ventral axis within this region. Moreover, region-of-interest analyses revealed that PM versus OG task only was associated with greater BOLD signal in left lateral rPFC, reflecting the requirement to maintain delayed intentions. Distinct aspects of this region were also transiently engaged at transitions between SO and SI conditions. These results are consistent with the hypothesis that some of the rostral prefrontal signal changes associated with PM performance reflect relative differences in SO versus SI processing.

A neural mechanism mediating the impact of episodic prospection on farsighted decisions.

Humans can vividly imagine possible future events. This faculty, episodic prospection, allows the simulation of distant outcomes and desires. Here, we provide evidence for the adaptive function of this capacity and elucidate its neuronal basis. Participants either imagined specific events of spending money (e.g., £ 35 in 180 days at a pub), or merely estimated what the money could purchase in the scenario. Imagining the future biased subsequent monetary decisions toward choices associated with a higher long-term pay-off. It thus effectively attenuated temporal discounting, i.e., the propensity to devalue rewards with a delay until delivery. Using functional magnetic resonance imaging, we implicate the medial rostral prefrontal cortex (mrPFC) in this effect. Blood oxygen level-dependent signal in this region predicted future-oriented choices on a trial-by-trial basis. Activation reflected the reward magnitude of imagined episodes, and greater reward sensitivity was related to less discounting. This effect was also associated with increased mrPFC-hippocampal coupling. The data suggest that mrPFC uses information conveyed by the hippocampus to represent the undiscounted utility of envisaged events. The immediate experience of the delayed reward value might then bias toward farsighted decisions.

Suppression weakens unwanted memories via a sustained reduction of neural reactivation.

Aversive events sometimes turn into intrusive memories. However, prior evidence indicates that such memories can be controlled via a mechanism of retrieval suppression. Here, we test the hypothesis that suppression exerts a sustained influence on memories by deteriorating their neural representations. This deterioration, in turn, would hinder their subsequent reactivation and thus impoverish the vividness with which they can be recalled. In an fMRI study, participants repeatedly suppressed memories of aversive scenes. As predicted, this process rendered the memories less vivid. Using a pattern classifier, we observed that suppression diminished the neural reactivation of scene information both globally across the brain and locally in the parahippocampal cortices. Moreover, the decline in vividness was associated with reduced reinstatement of unique memory representations in right parahippocampal cortex. These results support the hypothesis that suppression weakens memories by causing a sustained reduction in the potential to reactivate their neural representations.

Promoting farsighted decisions via episodic future thinking: A meta-analysis.

Episodic future thinking (EFT) denotes our capacity to imagine prospective events. It has been suggested to promote farsighted decisions that entail a trade-off between short-term versus long-term gains. Here, we meta-analyze the evidence for the impact of EFT on such intertemporal choices that have monetary or health-relevant consequences. Across 174 effect sizes from 48 articles, a three-level model yielded a medium-sized effect of g = .44, 95% (CI) [.33, .55]. Notably, this analysis included a substantial number of unpublished experiments, and the effect remained significant following further adjustments for remaining publication bias. We exploited the observed heterogeneity to determine critical core components that moderate the impact of EFT. Specifically, the effect was stronger when the imagined events were positive, more vivid, and related to the delayed choice. We further obtained evidence for the contribution of the episodicity and future-orientedness of EFT. These results indicate that the impact of EFT cannot simply be accounted for by other modes of prospection (e.g., semantic future thinking). Of note, EFT had a greater impact in samples characterized by choice impulsivity (e.g., in obesity), suggesting that EFT can ameliorate maladaptive decision making. It may accordingly constitute a beneficial intervention for individuals who tend to make myopic decisions. Our analyses moreover indicated that the effect is unlikely to merely reflect demand characteristics. This meta-analysis highlights the potential of EFT in promoting long-term goals, a finding that extends from the laboratory to real-life decisions. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Simulation-based learning influences real-life attitudes.

Humans can vividly simulate hypothetical experiences. This ability draws on our memories (e.g., of familiar people and locations) to construct imaginings that resemble real-life events (e.g., of meeting a person at a location). Here, we examine the hypothesis that we also learn from such simulated episodes much like from actual experiences. Specifically, we show that the mere simulation of meeting a familiar person (unconditioned stimulus; US) at a known location (conditioned stimulus; CS) changes how people value the location. We provide key evidence that this simulation-based learning strengthens pre-existing CS-US associations and that it leads to a transfer of valence from the US to the CS. The data thus highlight a mechanism by which we learn from simulated experiences.

Specialization of the rostral prefrontal cortex for distinct analogy processes.

Analogical reasoning is central to learning and abstract thinking. It involves using a more familiar situation (source) to make inferences about a less familiar situation (target). According to the predominant cognitive models, analogical reasoning includes 1) generation of structured mental representations and 2) mapping based on structural similarities between them. This study used functional magnetic resonance imaging to specify the role of rostral prefrontal cortex (PFC) in these distinct processes. An experimental paradigm was designed that enabled differentiation between these processes, by temporal separation of the presentation of the source and the target. Within rostral PFC, a lateral subregion was activated by analogy task both during study of the source (before the source could be compared with a target) and when the target appeared. This may suggest that this subregion supports fundamental analogy processes such as generating structured representations of stimuli but is not specific to one particular processing stage. By contrast, a dorsomedial subregion of rostral PFC showed an interaction between task (analogy vs. control) and period (more activated when the target appeared). We propose that this region is involved in comparison or mapping processes. These results add to the growing evidence for functional differentiation between rostral PFC subregions.

Memory suppression and its deficiency in psychological disorders: A focused meta-analysis.

It is still debated whether suppressing the retrieval of unwanted memories causes forgetting and whether this constitutes a beneficial mechanism. To shed light on these 2 questions, we scrutinize the evidence for such suppression-induced forgetting (SIF) and examine whether it is deficient in psychological disorders characterized by intrusive thoughts. Specifically, we performed a focused meta-analysis of studies that have used the think/no-think procedure to test SIF in individuals either affected by psychological disorders or exhibiting high scores on related traits. Overall, across 96 effects from 25 studies, we found that avoiding retrieval leads to significant forgetting in healthy individuals, with a small to moderate effect size (0.28, 95% CI [0.14, 0.43]). Importantly, this effect was indeed larger than for more anxious (-0.21, 95% CI [-0.41, -0.02]) or depressed individuals (0.05, 95% CI [-0.19, 0.29])-though estimates for the healthy may be inflated by publication bias. In contrast, individuals with a stronger repressive coping style showed greater SIF (0.42, 95% CI [0.32, 0.52]). Furthermore, moderator analyses revealed that SIF varied with the exact suppression mechanism that participants were instructed to engage. For healthy individuals, the effect sizes were considerably larger when instructions induced specific mechanisms of direct retrieval suppression or thought substitution than when they were unspecific. These results suggest that intact suppression-induced forgetting is a hallmark of psychological well-being, and that inducing more specific suppression mechanisms fosters voluntary forgetting. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

When I think about me and simulate you: medial rostral prefrontal cortex and self-referential processes.

While neuroimaging studies implicate medial rostral prefrontal cortex (mrPFC) in self-referential processing, simulation accounts of social cognition suggest that this region also supports thinking about other people. This study tested the prediction that mrPFC might be involved in appraising the personality traits of another person to the degree that this person is perceived as similar to oneself. We also examined whether recruiting common processes for thinking about oneself and others might impact on subsequent memory for those judgments. Functional MRI was used while two factors were crossed: (i) the requirement to engage in personality trait or episodic source memory judgments and (ii) the reference for these judgments (i.e., oneself or a friend). The results link haemodynamic changes in mrPFC to both personality judgments about oneself and subsequent episodic memory retrieval of these judgments. The degree to which BOLD signal in this region was also associated with thinking about others correlated with perceived similarity in both tasks, thus corroborating simulation accounts. Moreover, participants who perceived themselves as having similar traits to their friends tended to be poorer at remembering whether they had made trait judgments in reference to themselves or their friend. This behavioral effect was reflected in the BOLD signal in mrPFC: there was a positive correlation between signal change for self versus friend judgments and subsequent memory for the reference of such judgments. The results suggest that investigations of mrPFC activity in the context of self/other judgments should take into account this psychological similarity effect.

Distinct functional connectivity associated with lateral versus medial rostral prefrontal cortex: a meta-analysis.

Recent studies have shown that functional connectivity in the human brain may be detected by analyzing the likelihood with which different brain regions are simultaneously activated, or "co-activated", across multiple neuroimaging experiments. We applied this technique to investigate whether distinct subregions within rostral prefrontal cortex (RoPFC) tend to co-activate with distinct sets of brain regions outside RoPFC, in a meta-analysis of 200 activation peaks within RoPFC (approximating Brodmann Area 10) and 1712 co-activations outside this region, drawn from 162 studies. There was little evidence for distinct connectivity between hemispheres or along rostral/caudal or superior/inferior axes. However, there was a clear difference between lateral and medial RoPFC: activation in lateral RoPFC was particularly associated with co-activation in dorsal anterior cingulate, dorsolateral PFC, anterior insula and lateral parietal cortex; medial RoPFC activation was particularly associated with co-activation in posterior cingulate, posterior superior temporal sulcus and temporal pole. These findings are consistent with anatomical studies of connectivity in non-human primates, despite strong cross-species differences in RoPFC. Furthermore, associations between brain regions inside and outside RoPFC were in some cases strongly influenced by the type of task being performed. For example, dorsolateral PFC, anterior cingulate and lateral parietal cortex tended to co-activate with lateral RoPFC in most tasks but with medial RoPFC in tasks involving mentalizing. These results suggest the importance of changes in effective connectivity in the performance of cognitive tasks.