Threat Memory Research Articles

Stress promotes generalization of older but not recent threat memories

Stress broadly affects the ability to regulate emotions and may contribute to generalization of threat-related behaviors to harmless stimuli. Behavioral generalization also tends to increase over time as memory precision for recent events gives way to more gist-like representations. Thus, acute stress coupled with a delay in time from a negative experience may be a strong predictor of the transition from normal to generalized fear expression. Here, we investigated the effect of a single-episode acute stressor on generalization of aversive learning when stress is administered either immediately after an aversive learning event or following a delay. In a between-subjects design, healthy adult volunteers underwent threat (fear) conditioning using a tone-conditioned stimulus paired with an electric shock to the wrist and another tone not paired with shock. Behavioral generalization was tested to a range of novel tones either on the same day (experiment 1) or 24 h later (experiment 2) and was preceded by either an acute stress induction or a control task. Anticipatory sympathetic arousal [i.e., skin conductance responses (SCRs)] and explicit measures of shock expectancy served as dependent measures. Stress administered shortly after threat conditioning did not affect behavioral generalization. In contrast, stress administered following a delay led to heightened arousal and increased generalization of SCRs and explicit measures of shock expectancy. These findings show that acute stress increases generalization of older but not recent threat memories and have clinical relevance to understanding overgeneralization characteristics of anxiety and stress-related disorders.

Dissecting the Function of Hippocampal Oscillations in a Human Anxiety Model.

Neural oscillations in hippocampus and medial prefrontal cortex (mPFC) are a hallmark of rodent anxiety models that build on conflict between approach and avoidance. Yet, the function of these oscillations, and their expression in humans, remain elusive. Here, we used magnetoencephalography (MEG) to investigate neural oscillations in a task that simulated approach–avoidance conflict, wherein 23 male and female human participants collected monetary tokens under a threat of virtual predation. Probability of threat was signaled by color and learned beforehand by direct experience. Magnitude of threat corresponded to a possible monetary loss, signaled as a quantity. We focused our analyses on an a priori defined region-of-interest, the bilateral hippocampus. Oscillatory power under conflict was linearly predicted by threat probability in a location consistent with right mid-hippocampus. This pattern was specific to the hippocampus, most pronounced in the gamma band, and not explained by spatial movement or anxiety-like behavior. Gamma power was modulated by slower theta rhythms, and this theta modulation increased with threat probability. Furthermore, theta oscillations in the same location showed greater synchrony with mPFC theta with increased threat probability. Strikingly, these findings were not seen in relation to an increase in threat magnitude, which was explicitly signaled as a quantity and induced similar behavioral responses as learned threat probability. Thus, our findings suggest that the expression of hippocampal and mPFC oscillatory activity in the context of anxiety is specifically linked to threat memory. These findings resonate with neurocomputational accounts of the role played by hippocampal oscillations in memory.SIGNIFICANCE STATEMENT We use a biologically relevant approach–avoidance conflict test in humans while recording neural oscillations with magnetoencephalography to investigate the expression and function of hippocampal oscillations in human anxiety. Extending nonhuman studies, we can assign a possible function to hippocampal oscillations in this task, namely threat memory communication. This blends into recent attempts to elucidate the role of brain synchronization in defensive responses to threat.

The Power of Forgetting: Ressentiment, Guilt, and Transformative Politics

Though long regarded as an injustice in its own right, willed forgetting is currently enjoying something of a revival in politics. Concerned by the threat memory poses to both the peace and vitality of the state, critics have championed forgetting for its power to release us from ressentiment and begin anew. In this article, I take a closer look at Nietzsche's conception of willed forgetfulness, specifically as it is set out in On the Genealogy of Morals, to bring out what contemporary critics of the “surfeit of memory” seem happy to ignore: Namely, that a certain kind of cruelty, either against others or towards oneself, is the sine qua non of forgetting. Drawing on Freud as a supplement, I argue that many of the symptoms critics ascribe to the surfeit of memory—the culture of victimhood, the tyranny of guilt, the displacement of action, and the eclipse of visionary modes of imagining the future—may in actual fact be the product of forgetting.

Blocking human fear memory with the matrix metalloproteinase inhibitor doxycycline

Learning to predict threat is a fundamental ability of many biological organisms, and a laboratory model for anxiety disorders. Interfering with such memories in humans would be of high clinical relevance. On the basis of studies in cell cultures and slice preparations, it is hypothesised that synaptic remodelling required for threat learning involves the extracellular enzyme matrix metalloproteinase (MMP) 9. However, in vivo evidence for this proposal is lacking. Here we investigate human Pavlovian fear conditioning under the blood–brain barrier crossing MMP inhibitor doxycyline in a pre-registered, randomised, double-blind, placebo-controlled trial. We find that recall of threat memory, measured with fear-potentiated startle 7 days after acquisition, is attenuated by ~60% in individuals who were under doxycycline during acquisition. This threat memory impairment is also reflected in increased behavioural surprise signals to the conditioned stimulus during subsequent re-learning, and already late during initial acquisition. Our findings support an emerging view that extracellular signalling pathways are crucially required for threat memory formation. Furthermore, they suggest novel pharmacological methods for primary prevention and treatment of posttraumatic stress disorder.

Is autonoetic recollection of threat in PTSD related to impaired inhibitory skills?

IntroductionIntrusive traumatic reminiscences are among the most distressing and salient characteristics of post-traumatic stress disorder (PTSD). Associated with involuntary onsets, emotional disturbances and consciousness-related impairments, such symptoms suggest that memory functioning could be impaired in PTSD. While there is a growing body of research on experimental assessments of memory in patients with PTSD, inconsistent results remain.ObjectiveUsing an experimental methodology, this study aims to measure memory in PTSD in consideration of central features of intrusive symptoms, especially emotional, inhibitory and consciousness-related memory impairments.Method34 patients diagnosed with PTSD were compared with 37 non-PTSD controls on an item-cued directed forgetting paradigm for emotional words combined with a remember/know recognition procedure.ResultsResults confirmed prior findings of an increased and peculiarly conscious recognition of trauma-related words in PTSD. Interestingly, our results showed that, despite general memory inhibitory deficits, PTSD patients, if requested, presented a preserved ability to inhibit this improved recollection of trauma-related words.ConclusionWhile our findings highlight a biased memory functioning in favour of threatening stimuli in PTSD, inhibitory deficits for such information was not reported to play a role on this effect. Conversely, it seems that instead of inhibitory deficits, patients presented a preferential treatment of threat concordant with vigilant-avoidant models of information processing. Focusing on memory impairment in treatment for PTSD appears of prime importance. Our findings regarding preserved inhibitory skills for threat memories in the disorder could be an interesting clue for therapeutic interventions on intrusive symptoms.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Pre-trauma Methylphenidate in rats reduces PTSD-like reactions one month later

In basic research, the etiology of fear-related pathologies, such as post-traumatic stress disorder (PTSD), is conceptualized using fear-conditioning protocols that pair environmental stimuli (that is, a conditioned stimulus—CS) with an aversive, unconditioned stimulus (US) to elicit an assessable conditioned fear response. Although pathophysiological models agree that regulatory dysfunctions in this associative process may instigate fear-related pathology, current opinions differ in regard to the nature of these dysfunctions. Primarily derived from studies in rodents, the prevailing perspective proposes that pathological fear-reactions develop from intensified and overly consolidated CS-US associations. Alternatively, models derived from studies in humans suggest that tempospatial inaccuracies in representations of associative fear might precipitate pathology by engendering failure to differentiate present experiences and past memories of threat. To test this concept in rodents, we administered rats with cognition enhancing doses of Methylphenidate before or after fear conditioning and measured long-term alterations in their conditioned fear behaviors and PTSD-like reactions. The administration of Methylphenidate before fear-memory formation indeed reduced anxious-like responses during fear-memory retrieval one month later. An individual profiling analysis revealed that Methylphenidate onset had opposing effects on the risk for PTSD-like classification. The modulation of initial learning and formation of associative fear normalized the risk for developing PTSD-like reaction. In contrast, when the effects of Methylphenidate were exerted only over later consolidation this risk increased markedly. When examined under current psychiatric and neuropharmacologic literature, these results reveal a possible strategy of using low-dose Methylphenidate for the prevention of PTSD in high risk populations.

Primary auditory cortex regulates threat memory specificity.

Distinguishing threatening from nonthreatening stimuli is essential for survival and stimulus generalization is a hallmark of anxiety disorders. While auditory threat learning produces long-lasting plasticity in primary auditory cortex (Au1), it is not clear whether such Au1 plasticity regulates memory specificity or generalization. We used muscimol infusions in rats to show that discriminatory threat learning requires Au1 activity specifically during memory acquisition and retrieval, but not during consolidation. Memory specificity was similarly disrupted by infusion of PKMζ inhibitor peptide (ZIP) during memory storage. Our findings show that Au1 is required at critical memory phases and suggest that Au1 plasticity enables stimulus discrimination.

Amygdala-Cortical Connectivity: Associations with Anxiety, Development, and Threat.

Amygdala-prefrontal cortex (PFC) functional connectivity may be influenced by anxiety and development. A prior study on anxiety found age-specific dysfunction in the ventromedial PFC (vmPFC), but not amygdala, associated with threat-safety discrimination during extinction recall (Britton etal.). However, translational research suggests that amygdala-PFC circuitry mediates responses following learned extinction. Anxiety-related perturbations may emerge in functional connectivity within this circuit during extinction recall tasks. The current report uses data from the prior study to examine how anxiety and development relate to task-dependent amygdala-PFC connectivity. Eighty-two subjects (14 anxious youths, 15 anxious adults, 25 healthy youths, 28 healthy adults) completed an extinction recall task, which directed attention to different aspects of stimuli. Generalized psychophysiological interaction analysis tested whether task-dependent functional connectivity with anatomically defined amygdala seed regions differed across anxiety and age groups. Whole-brain analyses showed significant interactions of anxiety, age, and attention task (i.e., threat appraisal, explicit threat memory, physical discrimination) on left amygdala functional connectivity with the vmPFC and ventral anterior cingulate cortex (Talairach XYZ coordinates: -16, 31, -6 and 1, 36, -4). During threat appraisal and explicit threat memory (vs. physical discrimination), anxious youth showed more negative amygdala-PFC coupling, whereas anxious adults showed more positive coupling. In the context of extinction recall, anxious youths and adults manifested opposite directions of amygdala-vmPFC coupling, specifically when appraising and explicitly remembering previously learned threat. Future research on anxiety should consider associations of both development and attention to threat with functional connectivity perturbations.

Influence of Family and Childhood Memories in the Development and Manifestation of Paranoid Ideation.

Memories of family dynamics characterized by behaviours of antipathy from both parental figures, submissiveness and bullying victimization are important predictors of paranoid ideation in adult life. The study highlights the importance of exploring subjective recalls of feelings and behaviours associated with early rearing experiences, peer relationships and themes related to social rank theory in the roots of internal models of relationship with the self and others in the general sample, patients diagnosed with schizophrenia and their first-degree relatives. Our findings indicate that schizophrenic patients in active phase differ regarding memories of threat and submission and are more likely to remember childhood experiences perceived as threatening during an active phase than when in remission. It is possible that by changing these internal models and social interaction styles, patients may be able to get involved in more cooperating and affiliative interactions, disconfirming these early beliefs about others being rejecting, critical or hostile towards the self, and more effectively reducing the invalidation caused by positive and negative symptomatology of schizophrenia on social functioning.

Continuity and discontinuity in memory for threat

ABSTRACTUsing a paradigm that allows a quasi-continuous tracking of memory performance over time, two experiments were designed to test the hypotheses that (a) persons with a cognitively avoidant style of coping with threat manifest a dissociation between (intact) short-term and (reduced) long-term retrieval of aversive information and (b) persons with a vigilant coping style recall aversive information particularly well after long retention intervals, provided they are free to think about aversive events. Study 1 (N = 75) showed that avoiders manifest a poor memory for aversive pictures after long retention intervals only. Study 2 (N = 95) replicated this finding. In addition, manipulation of the cognitive load during the retention interval influenced vigilants’ recall of aversive information in the predicted way. Results indicate that processes occurring during the retention interval are essential for individual difference in memory for aversive information and require similar attention as encoding, appraisal, and retrieval processes.

Отражение во фразеологической неологии травматических исторических событий, связанных с террористической угрозой

Skorobogatova Taisiya Ivanovna, Nazarova Ekaterina Alexandrovna The article is devoted to the analysis of phraseological units - neologisms which are associated with such traumatic historical events, as the implementation of terrorist acts. Particular emphasis is placed on the description of English, Russian and French phraseological units that have introduced the memory of the terrorist threat in the XX-XXI centuries.: Eng. That’s so 10th September (lit. today September 10, fig: Do not worry ahead of time about nothing); Rus. мочить в сортире (descriptor: беспощадно расправиться); фр. le prince s’est mari, le m chant est mort, c’est une semaine Walt Disney (lit. prince married the villain died, week Walt Disney; descriptor: Idyll), g n ration Bataclan (lit. Bataklan generation; descriptor: young people age of the victims who died in the “Bataklane”, i.e. young people aged 25-35). Phraseology description of new, emerging units is one of the most important problems in theoretical linguistics, namely: to illustrate and confirm the fact that the phrasebook body of a single national language is the result of the two memories - historical and linguistic. At the same time important to consider such a significant factor that determines the specificity of the national phraseological fund as memory selectivity in general and historical memory in particular. Key words : phraseology, phraseological unit, phraseological neology, traumatic historical events, historical memory.

Editorial: How Fear and Stress Shape the Mind.

How do fear and stress systems interact and how do they shape ongoing and future behavioral responses? In a classical definition of fear and stress, we think of threatening stimuli activating a species-specific defensive threat reaction. This defensive reaction triggers physiological stress responses including adrenal hormone release (for review see LeDoux, 2003, 2012; Johnson et al., 2012). Knowledge of the microanatomy of conditioned threat memory is developing however, knowledge of its interaction with stress mediated adrenal steroid systems is still emerging (LeDoux, 2003, 2012; Johnson and LeDoux, 2004; Prager and Johnson, 2009; Prager et al., 2010; Bergstrom et al., 2011, 2013a,b; Bergstrom and Johnson, 2014; Krugers et al.). Studies have identified the key role of the lateral amygdala and within this nucleus the microanatomy of Pavlovian fear/threat memory consolidation, reconsolidation, and extinction has begun to be revealed (Bergstrom et al., 2011, 2013a,b; Bergstrom and Johnson, 2014). This Frontiers Research Topic builds on previous research by addressing key questions that reveal unique aspects and mechanisms of how fear and stress shape the mind.

Higher-Order Sensory Cortex Drives Basolateral Amygdala Activity during the Recall of Remote, but Not Recently Learned Fearful Memories.

How and where in the brain do we store the affective/motivational significance of sensory stimuli acquired through life experiences? Scientists have long investigated how "limbic" structures, such as the amygdala, process affective stimuli. Here we show that retrieval of well-established threat memories requires the functional interplay between higher-order components of the auditory cortex and the amygdala via synchrony in the theta range. This functional connectivity is a result of memory consolidation processes and is characterized by a predominant cortical to amygdala direction of information transfer. This connectivity is predictive of the animals' ability to recognize auditory stimuli as aversive. In the absence of this necessary cortical activity, the amygdala is unable to distinguish between frightening and neutral stimuli.

The Indirect Effect of Early Experiences on Deliberate Self-Harm in Adolescence: Mediation by Negative Emotional States and Moderation by Daily Peer Hassles

The present study examines whether early experiences of threat, subordination and devaluation with family influence adolescents’ negative emotional states and subsequently deliberate self-harm; and if this effect is conditioned by daily peer hassles. The sample consisted of 441 adolescents (57.6 % female) with ages between 13 and 18 years old from middle and high schools. Participants completed self-report instruments measuring early memories of threat, subordination and devaluation, daily peer hassles, negative affect and deliberate self-harm behaviors. Results from conditional process analysis showed that adolescents who feel devalued and experience threat and submission within family tend to endorse high levels of negative affect, which in turn accounts for increased endorsements on deliberate self-harm. Moreover, the impact of negative affect on deliberate self-harm is amplified by the presence of moderate and high levels of daily peer hassles. This study suggests the relevance of assessing and intervening on type of emotional memories (i.e., threat, subordination and devaluation), daily disruptions with peers and negative emotional states with adolescents who self-injure. These findings may be useful in the development of preventive and intervention programs for reducing deliberate self-harm in adolescence.

From Memory Impairment to Posttraumatic Stress Disorder-Like Phenotypes: The Critical Role of an Unpredictable Second Traumatic Experience

Arousal and stress critically regulate memory formation and retention. Increasing levels of stress produce an inverted U-shaped effect on cognitive performance, including the retention of explicit memories, and experiencing a severe stress during a traumatic event may lead to posttraumatic stress disorder (PTSD). The molecular mechanisms underlying the impairing effect of a severe stress on memory and the key contribution of traumatic experiences toward the development of PTSD are still unknown. Here, using increasing footshock intensities in an inhibitory avoidance paradigm, we reproduced the inverted U-shaped curve of memory performance in rats. We then show that the inverted U profile of memory performance correlates with an inverted U profile of corticosterone level in the circulation and of brain-derived neurotrophic factor, phosphorylated tropomyosin-receptor kinase B, and methyl CpG binding protein in the dorsal hippocampus. Furthermore, training with the highest footshock intensity (traumatic experience) led to a significant elevation of hippocampal glucocorticoid receptors. Exposure to an unpredictable, but not to a predictable, highly stressful reminder shock after a first traumatic experience resulted in PTSD-like phenotypes, including increased memory of the trauma, high anxiety, threat generalization, and resistance to extinction. Systemic corticosterone injection immediately after the traumatic experience, but not 3 d later, was sufficient to produce PTSD-like phenotypes. We suggest that, although after a first traumatic experience a suppression of the corticosterone-dependent response protects against the development of an anxiety disorder, experiencing more than one trauma (multiple hits) is a critical contributor to the etiology of PTSD.

Enhanced Memory for both Threat and Neutral Information Under Conditions of Intergroup Threat.

Few studies have examined the effect of intergroup threat on cognitive outcomes such as memory. Different theoretical perspectives can inform how intergroup threat should affect memory for threat-relevant and neutral information, such as the mood-congruency approach, Yerkes–Dodson law, Easterbrook’s theory, and also evolutionary perspectives. To test among these, we conducted two experiments to examine how exposure to intergroup threats affected memory compared to control conditions. In study 1, we manipulated symbolic threat and examined participants’ memory for threat and neutral words. In study 2, memory performance was assessed following the induction of realistic threat. Across the studies, in the control condition participants showed better memory for threat-related than neutral information. However, participants under threat remembered neutral information as well as threat-related information. In addition, participants in the threat condition remembered threat-related information as well as participants in the control condition. The findings are discussed in terms of automatic vigilance processes but also the effects of threat on arousal and its effect on information processing. This latter perspective, suggests paradoxically, that under some circumstances involving an outgroup threat, non-threatening information about outgroups can be extensively processed.

Acute administration of nicotine into the higher order auditory Te2 cortex specifically decreases the fear-related charge of remote emotional memories

Nicotine elicits several behavioural effects on mood as well as on stress and anxiety processes. Recently, it was found that the higher order components of the sensory cortex, such as the secondary auditory cortex Te2, are essential for the long-term storage of remote fear memories. Therefore, in the present study, we examined the effects of acute nicotine injection into the higher order auditory cortex Te2, on the remote emotional memories of either threat or incentive experiences in rats. We found that intra-Te2 nicotine injection decreased the fear-evoked responses to a tone previously paired with footshock. This effect was cue- and dose-specific and was not due to any interference with auditory stimuli processing, innate anxiety and fear processes, or with motor responses. Nicotine acts acutely in the presence of threat stimuli but it did not determine the permanent degradation of the fear-memory trace, since memories tested one week after nicotine injection were unaffected. Remarkably, nicotine did not affect the memory of a similar tone that was paired to incentive stimuli. We conclude from our results that nicotine, when acting acutely in the auditory cortex, relieves the fear charge embedded by learned stimuli.

Cognitive Biases in Pathological Health Anxiety

Pathological health anxiety refers to the medically unfounded fear of suffering from a severe illness. Differences in cognitive processes related to attention, memory, and evaluation of health threat have been hypothesized to underlie pathological health anxiety. In no study, however, have researchers systematically and simultaneously assessed different cognitive biases. On the basis of the idea that multiple cognitive biases simultaneously contribute to psychopathology (the combined-cognitive-bias hypothesis), we compared 88 patients with pathological health anxiety, 52 patients with depressive disorder, and 52 healthy participants on their performance in several cognitive tasks involving health-threatening content. Individuals with pathological health anxiety showed a stronger attentional bias to health-threat-related information, more negative explicit (but not implicit) evaluations of health threat, and biased response behavior in light of health threat. The results suggest that stronger bindings between feelings of arousal and health-threatening information in working memory might be crucial for the higher salience of health-threatening contents in pathological health anxiety.

Elucidating an Affective Pain Circuit that Creates a Threat Memory

Animals learn to avoid harmful situations by associating a neutral stimulus with a painful one, resulting in a stable threat memory. In mammals, this form of learning requires the amygdala. Although pain is the main driver of aversive learning, the mechanism that transmits pain signals to the amygdala is not well resolved. Here, we show that neurons expressing calcitonin gene-related peptide (CGRP) in the parabrachial nucleus are critical for relaying pain signals to the central nucleus of amygdala and that this pathway may transduce the affective motivational aspects of pain. Genetic silencing of CGRP neurons blocks pain responses and memory formation, whereas their optogenetic stimulation produces defensive responses and a threat memory. The pain-recipient neurons in the central amygdala expressing CGRP receptors are also critical for establishing a threat memory. The identification of the neural circuit conveying affective pain signals may be pertinent for treating pain conditions with psychiatric comorbidities.

Habitat stability, predation risk and 'memory syndromes'.

Habitat stability and predation pressure are thought to be major drivers in the evolutionary maintenance of behavioural syndromes, with trait covariance only occurring within specific habitats. However, animals also exhibit behavioural plasticity, often through memory formation. Memory formation across traits may be linked, with covariance in memory traits (memory syndromes) selected under particular environmental conditions. This study tests whether the pond snail, Lymnaea stagnalis, demonstrates consistency among memory traits (‘memory syndrome’) related to threat avoidance and foraging. We used eight populations originating from three different habitat types: i) laboratory populations (stable habitat, predator-free); ii) river populations (fairly stable habitat, fish predation); and iii) ditch populations (unstable habitat, invertebrate predation). At a population level, there was a negative relationship between memories related to threat avoidance and food selectivity, but no consistency within habitat type. At an individual level, covariance between memory traits was dependent on habitat. Laboratory populations showed no covariance among memory traits, whereas river populations showed a positive correlation between food memories, and ditch populations demonstrated a negative relationship between threat memory and food memories. Therefore, selection pressures among habitats appear to act independently on memory trait covariation at an individual level and the average response within a population.