Active suppression prevents the return of threat memory in humans.
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ABSTRACT:
SUBMITTER: Wang Y
PROVIDER: S-EPMC8139982 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Fear memories can be reactivated by a fear-associated conditioned stimulus (CS) or unconditioned stimulus (US) and then undergo reconsolidation. Propranolol administration during CS retrieval-induced reconsolidation can impair fear memory that is specific to the reactivated CS. However, from a practical perspective, the US is often associated with multiple CSs, and each CS can induce a fear response. The present study sought to develop and test a US-based memory retrieval interference procedure with propranolol to disrupt the original fear memory and eliminate all CS-associated fear responses in humans. We recruited 127 young healthy volunteers and conducted three experiments. All of the subjects acquired fear conditioning, after which they received the β-adrenergic receptor antagonist propranolol (40 mg) or placebo (vitamin C) and were exposed to the US or CS to reactivate the original fear memory. Fear responses were measured. Oral propranolol administration 1 h before US retrieval significantly decreased subsequent fear responses and disrupted associations between all CSs and the US. However, propranolol administration before CS retrieval only inhibited the fear memory that was related to the reactivated CS. Moreover, the propranolol-induced inhibition of fear memory reconsolidation that was retrieved by the US had a relatively long-lasting effect (at least 2 weeks) and was also effective for remote fear memory. These findings indicate that the US-based memory retrieval interference procedure with propranolol can permanently decrease the fear response and prevent the return of fear for all CSs in humans. This procedure may open new avenues for treating fear-related disorders.
| S-EPMC7555531 | biostudies-literature
Project description:Fear is prone to return following extinction that is the basis of exposure therapy for fear-related disorders. Manipulations that enhance the extinction process can be beneficial for treatment. Animal studies have shown that fasting or caloric restriction can enhance extinction and inhibit the return of fear. The present study examined the effects of fasting on fear acquisition, extinction, and the return of fear in humans. One hundred and twenty-five male participants were randomized into a fasting group and food group and exposed to a Pavlovian fear conditioning paradigm. Changes in plasma cortisol and ghrelin levels were examined using enzyme-linked immunosorbent assays. One-night fasting had no effect on fear acquisition but enhanced fear extinction retention and prevented the return of fear, and this effect persisted for at least 6 months. This procedure was also effective for remote fear memory. Plasma ghrelin levels were elevated after fasting and had a negative relationship with the fear response in spontaneous recovery test. However, overnight fasting did not affect cortisol levels. These findings indicate that fasting enhances extinction retention and prevents the return of fear, without influencing fear memory formation. We propose that this novel procedure may open new avenues for promoting extinction-based therapies for fear-related disorders.
| S-EPMC6177454 | biostudies-literature
Project description:RationaleMemories 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.ObjectivesThis study aimed to investigate the effects of OT administration following threat memory retrieval on subsequent memory expression in human participants.MethodsIn a double-blind, randomized, placebo-controlled, between-subject design, 61 healthy human individuals completed a 3-day experiment. All the participants underwent threat conditioning on day 1. On day 2, the 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, the participants were tested for extinction and reinstatement.ResultsOn 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 in stimulus discrimination by the late phase of extinction relative to the two other groups.ConclusionsThe 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.
| S-EPMC6374199 | biostudies-literature
Project description:Stereotype threat (ST) refers to a situation in which a member of a group fears that her or his performance will validate an existing negative performance stereotype, causing a decrease in performance. For example, reminding women of the stereotype "women are bad at math" causes them to perform more poorly on math questions from the SAT and GRE. Performance deficits can be of several types and be produced by several mechanisms. We show that ST prevents perceptual learning, defined in our task as an increasing rate of search for a target Chinese character in a display of such characters. Displays contained two or four characters and half of these contained a target. Search rate increased across a session of training for a control group of women, but not women under ST. Speeding of search is typically explained in terms of learned "popout" (automatic attraction of attention to a target). Did women under ST learn popout but fail to express it? Following training, the women were shown two colored squares and asked to choose the one with the greater color saturation. Superimposed on the squares were task-irrelevant Chinese characters. For women not trained under ST, the presence of a trained target on one square slowed responding, indicating that training had caused the learning of an attention response to targets. Women trained under ST showed no slowing, indicating that they had not learned such an attention response.
| S-EPMC2922584 | biostudies-literature
Project description:Previous electrophysiological studies in humans have shown rapid modulations of visual attention after conditioned threat vs. safety cues (<500 ms post-stimulus), but it is unknown whether this attentional prioritization is sustained throughout later time windows and whether it is robust to extinction. To investigate sustained visual attention, we assessed visuocortical alpha suppression in response to conditioned and extinguished threat. We reanalysed data from N = 87 male participants that had shown successful long-term threat conditioning and extinction in self reports and physiological measures in a two-day conditioning paradigm. The current EEG time-frequency analyses on recall test data on Day 2 revealed that previously threat-conditioned vs. safety cues evoked stronger occipital alpha power suppression from 600 to 1200 ms. Notably, this suppression was resistant to previous extinction. The present study showed for the first time that threat conditioning enhances sustained modulation of visuocortical attention to threat in the long term. Long-term stability and extinction resistance of alpha suppression suggest a crucial role of visuocortical attention mechanisms in the maintenance of learned fears.
| S-EPMC6825167 | biostudies-literature
Project description:The neural mechanisms and durability of Δ9-tetrahydrocannabinol (THC) impact on threat processing in humans are not fully understood. Herein, we used functional MRI and psychophysiological tools to examine the influence of THC on the mechanisms of conditioned threat extinction learning, and the effects of THC on extinction memory retention when assessed 1 day and 1 week from learning. Healthy participants underwent threat conditioning on day 1. On day 2, participants were randomized to take one pill of THC or placebo (PBO) 2-h before threat extinction learning. Extinction memory retention was assessed 1 day and 1 week after extinction learning. We found that THC administration increased amygdala and ventromedial prefrontal cortex (vmPFC) activation during early extinction learning with no significant impact on skin conductance responses (SCR). When extinction memory retention was tested 24 h after learning, the THC group exhibited lower SCRs to the extinguished cue with no significant extinction-induced activations within the extinction network. When extinction memory retention was tested 1 week after learning, the THC group exhibited significantly decreased responses to the extinguished cues within the vmPFC and amygdala, but significantly increased functional coupling between the vmPFC, hippocampus, and dorsal anterior cingulate cortex during this extinction retention test. Our results are the first to report a long-term impact of one dose of THC on the functional activation of the threat extinction network and unveil a significant change in functional connectivity emerging after a week from engagement. We highlight the need for further investigating the long-term impact of THC on threat and anxiety circuitry.
| S-EPMC6784991 | biostudies-literature
Project description:Humans shift their attention to follow another person's gaze direction, a phenomenon called gaze cueing. This study examined whether a particular social factor, intergroup threat, modulates gaze cueing. As expected, stronger responses of a particular in-group to a threatening out-group were observed when the in-group, conditioned to perceive threat from one of two out-groups, was presented with facial stimuli from the threatening and non-threatening out-groups. These results suggest that intergroup threat plays an important role in shaping social attention. Furthermore, larger gaze-cueing effects were found for threatening out-group faces than for in-group faces only at the 200 ms but not the 800 ms stimulus onset asynchrony (SOA); the specificity of the gaze-cueing effects at the short SOA suggests that threat cues modulate the involuntary component of gaze cueing.
| S-EPMC4360112 | biostudies-literature
Project description:Understanding how information about threats in the environment is shared and transmitted between individuals is crucial for explaining adaptive, survival-related behaviour in humans and other animals, and for developing treatments for phobias and other anxiety disorders. Research across species has shown that observing a conspecific's, a 'demonstrator's,' threat responses causes strong and persistent threat memories in the 'observer'. Here, we examined if physiological synchrony between demonstrator and observer can serve to predict the strength of observationally acquired conditioned responses. We measured synchrony between demonstrators' and observers' phasic electrodermal signals during learning, which directly reflects autonomic nervous system activity. Prior interpersonal synchrony predicted the strength of the observer's later skin conductance responses to threat predicting stimuli, in the absence of the demonstrator. Dynamic coupling between an observer's and a demonstrator's autonomic nervous system activity may reflect experience sharing processes facilitating the formation of observational threat associations.
| S-EPMC7287361 | biostudies-literature
Project description:Many fearful expectations are shaped by observation of aversive outcomes to others. Yet, the neurochemistry regulating social learning is unknown. Previous research has shown that during direct (Pavlovian) threat learning, information about personally experienced outcomes is regulated by the release of endogenous opioids, and activity within the amygdala and periaqueductal gray (PAG). Here we report that blockade of this opioidergic circuit enhances social threat learning through observation in humans involving activity within the amygdala, midline thalamus and the PAG. In particular, anticipatory responses to learned threat cues (CS) were associated with temporal dynamics in the PAG, coding the observed aversive outcomes to other (observational US). In addition, pharmacological challenge of the opioid receptor function is classified by distinct brain activity patterns during the expression of conditioned threats. Our results reveal an opioidergic circuit that codes the observed aversive outcomes to others into threat responses and long-term memory in the observer.
| S-EPMC5458514 | biostudies-literature
Project description:The ability to generalize from and distinguish between aversive memories and novel experiences is critical to survival. Previous research has revealed mechanisms underlying generalization of threat-conditioned defensive responses, but little is known about generalization of episodic memory for threatening events. Here we tested if aversive learning influences generalization of episodic memory for threatening events in human adults. Subjects underwent Pavlovian threat-conditioning in which objects from one category were paired with a shock and objects from a different category were unpaired. The next day, subjects underwent a recognition memory test that included old, highly similar, and entirely novel items from the shock-paired and shock-unpaired object categories. Results showed that items highly similar to those from the object category previously paired with shock were mistaken for old items more often than items from the shock-unpaired category. This finding indicates that threat learning promotes generalization of episodic memory, and is consistent with the idea that threat generalization is an active process that may be adaptive for avoiding a myriad of potential threats following an emotional experience. Enhanced generalization of aversive episodic memories may be maladaptive, however, when old threat memories are inappropriately reactivated in harmless situations, exemplified in a number of stress- and anxiety-related disorders. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
| S-EPMC6642861 | biostudies-literature