Search

Posttraumatic stress disorder (PTSD) is associated with altered pain perception, namely increased pain threshold and higher pain response. While pain consists of physiological and affective components, affective components are often overlooked. Similar patterns of increased threshold-high response in PTSD were shown in response to emotional stimuli, i.e., emotional numbing. As both emotional numbing and pain processing are modulated by the amygdala, we aimed to examine whether individuals diagnosed with PTSD show lower amygdala activation to pain compared with combat controls, and whether the amygdala responses to pain correlates with emotional numbing. To do so, two independent samples of veterans (original study: 44 total (20 PTSD); conceptual replication study: 40 total (20 PTSD)) underwent threat conditioning, where a conditioned stimulus (CS+; visual stimulus) was paired with an unconditioned stimulus (US; electric-shock). We contrasted the amygdala activity to the CS + US pairing with the CS+ presented alone and correlated it with emotional numbing severity. In both samples, the PTSD group showed a robust reduction in amygdala reactivity to shock compared to the Combat Controls group. Furthermore, amygdala activation was negatively correlated with emotional numbing severity. These patterns were unique to the amygdala, and did not appear in comparison to a control region, the insula, a pivotal region for the processing of pain. To conclude, amygdala response to pain is lower in individuals with PTSD, and is associated with emotional numbing symptoms. Lower amygdala reactivity to mild pain may contribute to the "all-or-none" reaction to stressful situations often observed in PTSD.

Measurement practice in experimental psychology is heterogeneous. Psychometric properties of measurement methods are sometimes difficult to establish, leaving researchers with few criteria to select between methods. To overcome this obstacle, calibration is a standard metrological procedure in which well-defined values of a latent variable are generated in an established experimental paradigm. These intended values can then serve as validity criterion, to rank methods by their measurement error. This approach requires community consensus on which calibration experiment to use. Here, we develop a consensus process and exemplify it in the field of human fear conditioning. Based on a literature review and survey of N = 96 experts, we propose a calibration experiment and settings for 25 design variables to calibrate the measurement of "learned unconditioned-stimulus (US) expectation". This latent variable and the calibration procedure were chosen to be as theory-free as possible, and to have the widest experimental applicability among the surveyed researchers. Besides establishing a specific calibration procedure for fear conditioning, the general calibration process we outline may serve as a blueprint for calibration efforts in other subfields of experimental psychology that are in need of measurement refinement.

All addictive disorders consist of two key, interacting features: persistent subjective craving and maladaptive choice behaviors. However, the computations underlying the bidirectional relationship between craving and decision-making remain unknown. Here, we tested a hypothesis that momentary craving and value-based decision-making dynamically influence each other across addictive domains. We sampled momentary craving as three groups of participants (alcohol drinkers, cannabis users, and binge eaters; totaln=202) performed a probabilistic learning task in which they received either monetary or group-specific addictive cue rewards. Using computational modeling, we found that momentary craving dynamically biased towards faster learning during addictive but not monetary decision-making across all groups. Conversely, we also found that prediction errors modulated perceived craving. Computational parameters underlying these latent mechanisms were reliably predictive of clinical severity. These findings provide a computational mechanism for the interaction between craving and choice behavior that is generalizable across addictive domains.

Finding positive meaning in past negative memories is associated with enhanced mental health. Yet it remains unclear whether it leads to updates in the memory representation itself. Since memory can be labile after retrieval, this leaves the potential for modification whenever its reactivated. Across four experiments, we show that positively reinterpreting negative memories adaptively updates them, leading to the re-emergence of positivity at future retrieval. Focusing on the positive aspects after negative recall leads to enhanced positive emotion and changes in memory content during recollection one week later, remaining even after two months. Consistent with a reactivation-induced reconsolidation account, memory updating occurs only after a reminder and twenty four hours, but not a one hour delay. Multi-session fMRI showed adaptive updates are reflected in greater hippocampal and ventral striatal pattern dissimilarity across retrievals. This research highlights the mechanisms by which updating of maladaptive memories occurs through a positive emotion-focused strategy., Finding positive meaning in past negative events is associated with enhanced mental health. Here the authors show this adaptively updates memory, leading to enhanced positive emotion and content at future retrieval, which remains two months later.

For people with post-traumatic stress disorder (PTSD), recalling traumatic memories often displays as intrusions that differ profoundly from processing of ‘regular’ negative memories. These mnemonic features fueled theories speculating a qualitative divergence in cognitive state linked with traumatic memories. Yet to date, little empirical evidence supports this view. Here, we examined neural activity of PTSD patients who were listening to narratives depicting their own memories. An inter-subject representational similarity analysis of cross-subject semantic content and neural patterns revealed a differentiation in hippocampal representation by narrative type: Semantically similar sad autobiographical memories elicited similar neural representations across participants. By contrast, within the same individuals, semantically thematically similar trauma memories were not represented similarly. Furthermore, we were able to decode memory type from hippocampal multivoxel patterns. Finally, individual symptom severity modulated semantic representation of the traumatic narratives in the posterior cingulate cortex. Taken together, these findings suggest that traumatic memories are a qualitatively divergent cognitive entity.

During navigation, the hippocampus represents physical places like coordinates on a map; similar location-like signals have been seen in sensory and concept spaces. It is unclear just how general this hippocampal place code is, however: does it map places in wholly non-perceivable spaces, without locations being instructed or reinforced and during navigation-like behavior? To search for such a signal, we imaged participants’ brains while they played a naturalistic, narrativebased social interaction game, and modeled their relationships as a kind of navigation through social space. Two independent samples showed hippocampal place-like signals in both region-based and whole-brain representational similarity analyses, as well as decoding and average pattern similarity analyses; the effects were not explained by other measures of the behavior or task information. These results are the first demonstration of complete domain generality in hippocampal place representation.One-Sentence Summaryhippocampal place-like signal in non-perceivable and unreinforced space during naturalistic navigational behavior.Significance statementThe hippocampus is a brain structure known to encode maps of physical spaces; this study shows that it also maps fully abstract, latent and uninstructed spaces. People played a naturalistic social interaction game while their brains were scanned. Hippocampal brain activity correlated with the fictional characters’ locations in an abstract social space framed by axes of affiliation and power, despite the participants never being exposed to a perceivable spatial representation. This mapping was present across multiple analyses and two samples, demonstrating that the brain system responsible for spatial mapping maps our social interactions too.

Reading scientific papers is a necessary part of the research enterprise, but poor writing impedes the flow of information from authors to their audiences. We argue that a return to narrative in scientific writing is not incompatible with rigour and objectivity; it can mitigate information overload and achieve the core purpose of publication: to communicate.

We present here a unifying framework for affective phenomena: the Human Affectome. By synthesizing a large body of literature, we have converged on definitions that disambiguate the commonly used terms—affect, feeling, emotion, and mood. Based on this definitional foundation, and under the premise that affective states reflect allostatic concerns, we take a goal-directed, enactive perspective. The human affectome is comprised of allostatic features (valence, motivation, and arousal) and allostatic concerns, which differ in the amount of action required to alleviate allostatic load. Allostatic concerns often fall into three ranges: physiological (the most immediate), operational (intermediate to distal), and global. Global concerns involve summations of overall trajectory, general wellbeing, and self-identity. Within this organizational scheme, the human affectome allows vastly different scientific interests to reside within the same theoretical framework and relate to each other. We hope this framework serves as a common focal point for affective research.

Background Evidence suggests that extinction during memory reconsolidation diminishes the return of defensive responses. In order to translate these effects to the clinical setting, we tested whether retrieving a traumatic memory and delivering a brief two-sessions imaginal exposure intervention during its reconsolidation would produce stronger decreases in reactivity to these memories than standard imaginal exposure method. Methods Participants with Post-Traumatic Stress Disorder (PTSD) had either their traumatic (n = 21) or a neutral (n = 21) memory retrieved 1 hour before an imaginal exposure session for two consecutive days. One day before and one day after, participants were exposed to script-driven imagery of their traumatic event, during which skin conductance responses were measured and, immediately after, subjective responses were assessed by means of Visual Analogue Scales. Results Traumatic retrieval improved the physiological, but not the subjective effects of imaginal exposure intervention on over-reactivity to traumatic memories. Conclusions Our results suggest that delivering extinction-based treatments over the reconsolidation of traumatic memories may enhance its effects. These results suggest that this is a promising path toward the development of new therapeutic techniques.

Cannabis is one of the most widely used substances in the world, with usage trending upward in recent years. However, although the psychiatric burden associated with maladaptive cannabis use has been well established, reliable and interpretable biomarkers associated with chronic use remain elusive. In this study, we combine large-scale functional magnetic resonance imaging with machine learning and network analysis and develop an interpretable decoding model that offers both accurate prediction and novel insights into chronic cannabis use.Chronic cannabis users (n = 166) and nonusing healthy control subjects (n = 124) completed a cue-elicited craving task during functional magnetic resonance imaging. Linear machine learning methods were used to classify individuals into chronic users and nonusers based on whole-brain functional connectivity. Network analysis was used to identify the most predictive regions and communities.We obtained high (∼80% out-of-sample) accuracy across 4 different classification models, demonstrating that task-evoked connectivity can successfully differentiate chronic cannabis users from nonusers. We also identified key predictive regions implicating motor, sensory, attention, and craving-related areas, as well as a core set of brain networks that contributed to successful classification. The most predictive networks also strongly correlated with cannabis craving within the chronic user group.This novel approach produced a neural signature of chronic cannabis use that is both accurate in terms of out-of-sample prediction and interpretable in terms of predictive networks and their relation to cannabis craving.

As an academic pursuit, neuroscience is enjoying a golden age. From a clinical perspective, our field is failing. Conventional 20th century drugs and devices are not well-matched to the heterogeneity, scale, and connectivity of neural circuits that produce aberrant mental states and behavior. Laboratory-based methods for editing neural genomes and sculpting activity patterns are exciting, but their applications for hundreds of millions of people with mental health disorders is uncertain. We argue that mechanisms for regulating adult brain plasticity and remodeling pathological activity are substantially pre-wired, and we suggest new minimally invasive strategies to harness and direct these endogenous systems. Drawing from studies across the neuroscience literature, we describe approaches that identify neural biomarkers more closely linked to upstream causes-rather than downstream consequences-of disordered behavioral states. We highlight the potential for innovation and discovery in reverse engineering approaches that refine bespoke behavioral "agonists" to drive upstream neural biomarkers in normative directions and reduce clinical symptoms for select classes of neuropsychiatric disorders.

Autism spectrum disorder (ASD) is characterized by hallmark impairments in social functioning. Nevertheless, nonsocial cognition, including hippocampus-dependent spatial reasoning and episodic memory, is also commonly impaired in ASD. ASD symptoms typically emerge between 12 and 24 months of age, a time window associated with critical developmental events in the hippocampus. Despite this temporal overlap and evidence of hippocampal structural abnormalities in ASD individuals, relatively few human studies have focused on hippocampal function in ASD. Herein, we review the existing evidence for the involvement of the hippocampus in ASD and highlight the hippocampus as a promising area of interest for future research in ASD.

By combining computational, morphological, and functional analyses, this study relates latent markers of associative threat learning to overt post-traumatic stress disorder (PTSD) symptoms in combat veterans. Using reversal learning, we found that symptomatic veterans showed greater physiological adjustment to cues that did not predict what they had expected, indicating greater sensitivity to prediction errors for negative outcomes. This exaggerated weighting of prediction errors shapes the dynamic learning rate (associability) and value of threat predictive cues. The degree to which the striatum tracked the associability partially mediated the positive correlation between prediction-error weights and PTSD symptoms, suggesting that both increased prediction-error weights and decreased striatal tracking of associability independently contribute to PTSD symptoms. Furthermore, decreased neural tracking of value in the amygdala, in addition to smaller amygdala volume, independently corresponded to higher PTSD symptom severity. These results provide evidence for distinct neurocomputational contributions to PTSD symptoms.

BackgroundPsychiatric neuroimaging typically proceeds with one of two approaches: encoding models, which aim to model neural mechanisms, or decoding models, which aim to predict behavioral or clinical characteristics from brain imaging data. In this study, we seek to combine these aims by developing interpretable decoding models that offer both accurate prediction and novel neural insights. We demonstrate the effectiveness of this combined approach in a case study of chronic marijuana use.MethodsChronic marijuana (MJ) users (n=195) and non-using healthy controls (n=128) completed a cue-elicited craving task during functional magnetic resonance imaging. Linear machine learning methods were used to classify individuals into chronic MJ users and non-users based on task-evoked, whole-brain functional connectivity. We then used graph theoretic analyses to identify ‘predictive functional connectivities’ among brain regions that contributed most substantially to the classification of chronic marijuana use.ResultsWe obtained high (~80% out-of-sample) accuracy across four different classification models, demonstrating that task-evoked, whole-brain functional connectivity can successfully differentiate chronic marijuana users from non-users. Subsequent network analyses revealed key predictive regions (e.g., anterior cingulate cortex, dorsolateral prefrontal cortex, and precuneus) that are often implicated in neuroimaging studies of substance use disorders, as well as some key exceptions. We also identified a core set of networks of brain regions that contributed to successful classification, comprised of many of the same predictive regions.ConclusionsOur dual aims of accurate prediction and interpretability were successful, producing a predictive model that also provides interpretability at the neural level. This novel approach may complement other predictive-exploratory approaches for a more complete understanding of neural mechanisms in drug use and other neuropsychiatric disorders.

Misophonia is a disorder of decreased tolerance to specific sounds or their associated stimuli that has been characterized using different language and methodologies. The absence of a common understanding or foundational definition of misophonia hinders progress in research to understand the disorder and develop effective treatments for individuals suffering from misophonia. From June 2020 through January 2021, a project was conducted to determine whether a committee of experts with diverse expertise related to misophonia could develop a consensus definition of misophonia. An expert committee used a modified Delphi method to evaluate candidate definitional statements that were identified through a systematic review of the published literature. Over four rounds of iterative voting, revision, and exclusion, the committee made decisions to include, exclude, or revise these statements in the definition based on the currently available scientific and clinical evidence. A definitional statement was included in the final definition only after reaching consensus at 80% or more of the committee agreeing with its premise and phrasing. The results of this rigorous consensus-building process were compiled into a final definition of misophonia that is presented here. This definition will serve as an important step to bring cohesion to the growing field of researchers and clinicians who seek to better understand and support individuals experiencing misophonia.

BackgroundProblems in learning that sights, sounds, or situations that were once associated with danger have become safe (extinction learning) may explain why some individuals suffer prolonged psychological distress following traumatic experiences. Although simple learning models have been unable to provide a convincing account of why this learning fails, it has recently been proposed that this may be explained by individual differences in beliefs about the causal structure of the environment.MethodsHere, we tested two competing hypotheses as to how differences in causal inference might be related to trauma-related psychopathology, using extinction learning data collected from clinically well-characterised individuals with varying degrees of post-traumatic stress (N = 56). Model parameters describing individual differences in causal inference were related to multiple post-traumatic stress disorder (PTSD) and depression symptom dimensions via network analysis.ResultsIndividuals with more severe PTSD were more likely to assign observations from conditioning and extinction stages to a single underlying cause. Specifically, greater re-experiencing symptom severity was associated with a lower likelihood of inferring that multiple causes were active in the environment.ConclusionsWe interpret these results as providing evidence of a primary deficit in discriminative learning in participants with more severe PTSD. Specifically, a tendency to attribute a greater diversity of stimulus configurations to the same underlying cause resulted in greater uncertainty about stimulus-outcome associations, impeding learning both that certain stimuli were safe, and that certain stimuli were no longer dangerous. In the future, better understanding of the role of causal inference in trauma-related psychopathology may help refine cognitive therapies for these disorders.

A recent article in the journal Cortex (Chalkia et al. 2020) has claimed a failure to verify the results reported in our 2010 study describing the phenomenon of reconsolidation updating using the retrieval-extinction protocol (Schiller et al., 2010). Since the journal did not grant us the right of reply, we publish our response here. We show, among other things, that a reanalysis of the raw data reproduces the results and contend that the conclusions are valid.

Unbidden distressing memories inflict serious damage on mental health. Extant research highlights the importance of associative learning in modulating aversive memory. We report that conscious active suppression eliminates learned fear responses independent of memory triggers and is related to individual difference in thought control ability; in contrast, thought diversion only reduces cue-specific fear response. These results suggest potential avenues for treatment of persistent maladaptive memories by engaging declarative mnemonic control mechanisms., Ye Wang et al. show that conscious thought active suppression eliminates learned fear responses whereas thought diversion only reduces cue-specific fear response. This study suggests that declarative control mechanisms may be utilized to treat persistent maladaptive memories.

A serious lack of effective pharmacotherapeutic interventions for posttraumatic stress disorder (PTSD) raises the urgent need for the development of novel treatments. Ketamine-a noncompetitive glutamate N-methyl-d-aspartate (NMDA) receptor antagonist in use for decades as an anesthetic and analgesic agent-has more recently been demonstrated to have rapid-onset antidepressant effects in patients with treatment-resistant depression (TRD). In the present review of ketamine as an emerging novel pharmacotherapeutic intervention for chronic PTSD, we discuss findings from the first proof-of-concept, randomized clinical trial (RCT) of single-dose intravenous ketamine in patients with chronic PTSD, as well as open-label studies and current practice. We introduce ongoing RCTs investigating the efficacy of repeated ketamine infusions in rapidly reducing symptoms and maintaining improvement in samples of individuals with PTSD stemming from civilian and military traumas. Additionally, we discuss mixed findings from published reports on ketamine administration in the acute aftermath of trauma. Studies in animal models of chronic stress have investigated molecular mechanisms underlying ketamine's effects, generating a shift in the conceptualization of PTSD as a disorder of impaired neural connectivity. We review animal studies examining the potential of ketamine to modify the expression of fear by altering memory reconsolidation or enhancing fear extinction, as well as others investigating ketamine administration prophylactically prior to stress exposure. We introduce the need for additional study in humans to evaluate whether ketamine might enhance the efficacy of psychotherapeutic interventions in individuals with chronic PTSD, harnessing a window of ketamine-induced neuroplasticity. While research on ketamine for PTSD is still in its early stages, it brings about the promise of novel and more effective treatments for this disabling condition.

A serious lack of effective pharmacotherapeutic interventions for posttraumatic stress disorder (PTSD) raises the urgent need for the development of novel treatments. Ketamine-a noncompetitive glutamate N-methyl-d-aspartate (NMDA) receptor antagonist in use for decades as an anesthetic and analgesic agent-has more recently been demonstrated to have rapid-onset antidepressant effects in patients with treatment-resistant depression (TRD). In the present review of ketamine as an emerging novel pharmacotherapeutic intervention for chronic PTSD, we discuss findings from the first proof-of-concept, randomized clinical trial (RCT) of single-dose intravenous ketamine in patients with chronic PTSD, as well as open-label studies and current practice. We introduce ongoing RCTs investigating the efficacy of repeated ketamine infusions in rapidly reducing symptoms and maintaining improvement in samples of individuals with PTSD stemming from civilian and military traumas. Additionally, we discuss mixed findings from published reports on ketamine administration in the acute aftermath of trauma. Studies in animal models of chronic stress have investigated molecular mechanisms underlying ketamine's effects, generating a shift in the conceptualization of PTSD as a disorder of impaired neural connectivity. We review animal studies examining the potential of ketamine to modify the expression of fear by altering memory reconsolidation or enhancing fear extinction, as well as others investigating ketamine administration prophylactically prior to stress exposure. We introduce the need for additional study in humans to evaluate whether ketamine might enhance the efficacy of psychotherapeutic interventions in individuals with chronic PTSD, harnessing a window of ketamine-induced neuroplasticity. While research on ketamine for PTSD is still in its early stages, it brings about the promise of novel and more effective treatments for this disabling condition.

Delay discounting describes the phenomenon whereby the subjective value of a reward declines as the time until its receipt increases. Individuals differ in the subjective value that they assign to future rewards, yet, the components feeding into this appraisal of value remain unclear. We examined whether temporal psychological distance, i.e. the closeness one feels to the past and future, is one such component. English speakers in the USA and Mandarin speakers in China completed a delay discounting task and organized past and future world events on a canvas according to their representation of the event’s temporal position relative to themselves. Previous work has identified linguistic and cultural differences in time conception between these populations, thus, we hypothesized that this sample would display the variability necessary to probe whether temporal psychological distance plays a role in reward valuation. We found that English speakers employed horizontal, linear representations of world events, while Mandarin speakers used more two-dimensional, circular representations. Across cultures, individuals who represented the future as more distant discounted future rewards more strongly. Distance representations of past events, however, were associated with discounting behaviors selectively in Mandarin speakers. This suggests that temporal psychological distance plays a fundamental role in farsighted decision-making.

Food avoidance in anorexia nervosa (AN) has been hypothesized to occur as a result of deficits in reversal learning and altered neuronal processing of food—cue relationships. Extant findings suggest that those with AN may rely on heightened recruitment of prefrontal regions during initial formation of food—cue learning and difficulty extinguishing these relationships may result from elevated insula activity. We tested this hypothesis by comparing behavioral and neuronal responses to food—cue acquisition and reversal between adolescents with AN and healthy controls. Compared to controls, acquisition of a food—cue association and its reversal were associated with elevated prefrontal activation in adolescents with AN. There were no significant differences between groups in insula activation and no behavioral differences in the ability to acquire or reverse the food—cue association. The results suggest that adolescents with AN recruit prefrontal regulatory networks to acquire and alter expectancies to food. This pattern of top-down prefrontal control suggests that clinical interventions that target changes in food—cue relationships and rely on cognitive control may be less effective. Interventions that alter behavior without reliance on this top-down control may have advantages with this population.

Threat extinction is the decline in responding to a stimulus that previously signaled danger, following repeated non-consequential exposures. The amygdala, prefrontal cortex, and hippocampus are known contributors to the neural circuits driving threat extinction, however, research has not yet resolved the precise neuronal interactions necessary for extinction success. At times, research even appears to present conflicting conclusions concerning the neurocircuitry that drives extinction learning. Here, we propose a model of threat extinction that accounts for the range of findings within the literature. Our model consists of two parallel pathways that differ in their temporal dynamics, such that a fast extinction circuit requires only one training session and exerts its effects rapidly, while a slow circuit impacts behavior only after multiple training sessions. This dual-mechanism of threat extinction circuits is rooted in a hybrid associative learning model whereby parallel fast and slow pathways differentially rely on new learning and unlearning, respectively, to optimize survival as an animal’s probabilistic beliefs concerning threat and danger evolve over repeated extinction trials.

RATIONALE. Memories can return to a labile state and become amenable to modification by pharmacological and behavioral manipulations after retrieval. This process may reduce the impact of aversive memories and provide a promising therapeutic technique for the treatment of anxiety disorders. A growing body of evidence suggests that the mammalian neuropeptide oxytocin (OT) plays a role in the regulation of emotional memories in animals. However, the effects of OT on threat memory in humans remain largely unknown. OBJECTIVES. This study aimed to investigate the effects of OT administration following threat memory retrieval on subsequent memory expression in human participants. METHODS. In a double blind, randomized, placebo-controlled, between-subject design, 61 healthy human individuals completed a three-day experiment. All participants underwent threat conditioning on day 1. On day 2, participants were randomized to receive an intranasal dose of OT (40 IU) or placebo after memory retrieval, or an intranasal dose of OT (40 IU) without retrieval. On day 3, subjects were tested for extinction and reinstatement. RESULTS. On day 3, all groups showed equivalent stimulus discrimination during the early phase of extinction. However, the group that received OT following a memory reminder showed a greater decline of stimulus discrimination by the late phase of extinction relative to the two other groups. CONCLUSIONS. The results indicate that OT did not block reconsolidation to prevent the return of threat memory but rather interacted with post-retrieval processes to facilitate next day extinction. The study provides novel preliminary evidence for the role of OT in human threat memory.

The concept of cognitive map has been proposed as a way to organize our experiences and guide behavior across all domains of cognition. The hippocampus has been identified as the neural substrate supporting cognitive maps for navigating physical space. Recent evidence is broadening the role of the hippocampus into mapping other manner of spaces. Here we focus on the case of social space as a candidate for hippocampal representation because it combines multiple continuous dimensions and requires dynamic navigation through social contexts. We present evidence for the role of the hippocampus in (1) supporting social memory, (2) representing different dimensions of social space, (3) tracking dynamic social behavior, (4) maintaining a flexible map allowing adaptation to new social contexts, and (5) maladaptive social behavior across psychiatric disorders. To do so, we explore evidence across species including birds, rodents, nonhuman primates and humans, indicating hippocampal involvement in a range of social processes. Review of previous findings in a manner predicted by the cognitive map supports the existence of systematic mapping of social space by the hippocampus. Evidence for hippocampal social maps complements findings from other abstract domains, such as auditory, temporal and conceptual, allowing successful navigation through many domains of everyday life.

The reactivation of a synaptically stored memory in the brain can make the memory transiently labile. During the time it takes for the memory to re-stabilize (reconsolidate), the memory can either be reduced by an amnesic agent or enhanced by memory enhancers. The change in memory expression is related to changes in the brain correlates of long-term memory. Many have suggested that such retrieval-induced plasticity is ideally placed to enable memories to be updated with new information. This hypothesis has been tested experimentally, with a translational perspective, by attempts to update maladaptive memories in order to reduce their problematic impact. Here, we review the progress on reconsolidation-update studies, highlighting their translational exploitation and addressing recent challenges to the reconsolidation field.

Anxiety and trauma related disorders are highly prevalent, causing suffering and high costs for society. Current treatment strategies, although effective, only show moderate effect-sizes when compared to adequate control groups demonstrating a need to develop new forms of treatment or optimize existing ones. In order to achieve this, an increased understanding of what mechanisms are involved is needed. An emerging literature indicates that mindfulness training (MFT) can be used to treat fear and anxiety related disorders, but the treatment mechanisms are unclear. One hypothesis, largely based on findings from neuroimaging studies, states that MFT may improve extinction retention, but this has not been demonstrated empirically. To investigate this question healthy subjects either completed a 4-week MFT- intervention delivered through a smart-phone app (n = 14) or were assigned to a waitlist (n = 15). Subsequently, subjects participated in a two-day experimental protocol using pavlovian aversive conditioning, evaluating acquisition and extinction of threat-related responses on day 1, and extinction retention on day 2. Results showed that the MFT group displayed reduced spontaneous recovery of threat related arousal responses, as compared to the waitlist control group, on day 2. MFT did not however, have an effect on either the acquisition or extinction of conditioned responses day 1. This clarifies the positive effect of MFT on emotional functioning and could have implications for the treatment of anxiety and trauma related disorders.

Social deficits, such as poor social skills (i.e., the inability to engage in appropriate and effective social interactions) and social withdrawal, are prevalent across psychiatric disorders and often co-occur with hippocampal structural and functional abnormalities. The centrality of both social and hippocampal dysfunction in psychiatric research prompts the question: Are they linked? The social cognitive map framework provides a clue: The hippocampus tracks social information in the physical environment, maps others along social dimensions, and supports social memory and decision-making. Hippocampal dysfunction might disrupt social map representation and contribute to commonly seen social behavioral symptoms. This review summarizes evidence for the role of the hippocampus in social cognitive mapping, followed by evidence that hippocampal dysfunction and social dysfunction co-occur in psychiatric disorders. We argue that the co-occurrence of hippocampal and social impairment may be related via hippocampal social cognitive mapping.

To achieve greatest efficacy, therapies for attenuating fear and anxiety should preclude the re-emergence of emotional responses. Of relevance to this aim, preclinical models of threat memory reduction are considered to engage one of two discrete neural processes: either establishment of a new behavioral response that competes with, and thereby temporarily interferes with expression of, an intact threat memory (new learning), or one which modifies and thereby disrupts an intact threat memory (unlearning). We contend that a strict dichotomy of new learning and unlearning does not provide a compelling explanation for current data. Instead, we suggest the evidence warrants consideration of alternative models that assume cooperation rather than competition between formation of new cellular traces and the modification of preexisting ones.

In an ever-changing environment, survival depends on learning which stimuli represent threat, and also on updating such associations when circumstances shift. Humans can acquire physiological responses to threat-associated stimuli even when they are unaware of them, but the role of awareness in updating threat contingencies remains unknown. This complex process – generating novel responses while simultaneously suppressing learned ones – relies on distinct neural mechanisms from initial learning, and has only been shown with awareness. Can it occur unconsciously? Here we show that it can. Participants underwent classical threat conditioning to visual stimuli that were suppressed from their awareness. One of two images was paired with an electric shock; halfway through the experiment, contingencies were reversed and the shock was paired with the other image. We found that physiological responses reflected changes in stimulus-threat pairings independently of stimulus awareness, demonstrating the sophistication of unconscious affective flexibility.