Effect of alcohol on the sense of agency in healthy humans.

Even at low to moderate doses, ingestion of the widely used recreational drug alcohol (ethanol) can impact cognitive and emotional processing. Recent studies show that the sense of agency (SoA; ie, the subjective experience of voluntary control over actions) can be modulated by specific pharmacological manipulations. The SoA, as quantified by the intentional binding (IB) paradigm, is enhanced by direct or indirect dopaminergic agonists in patients with Parkinson's disease and by ketamine (an N-methyl-D-aspartate (NMDA) receptor antagonist) in healthy individuals. These findings implicate dopaminergic and glutamatergic neurotransmission in mechanisms underlying SoA. Alcohol has a complex set of actions, including disinhibition of dopaminergic neurotransmission and allosteric antagonism at NMDA receptors. Here, we tested the hypothesis that low to moderate doses of alcohol would enhance SoA, and impact impulsivity and subjective emotional state. We conducted two experiments in 59 healthy male and female social drinkers, who ingested either a placebo "vehicle," or one of two doses of ethanol: 0.4 and 0.6 g/kg. In both experiments, we observed increased SoA/IB at both doses of alcohol exposure, relative to the placebo condition. We found no correlation between the effects of alcohol on IB and on impulsivity or subjective emotional state. Our findings might have implications for social and legal responsibility related to alcohol use, particularly in states prior to overt intoxication. Further studies are necessary to investigate the effects of alcohol and other addictive substances on the SoA.

Knowledge about the predictive value of reward conditioned stimuli modulates their interference with cognitive processes.

Stimuli conditioned with a substance can generate drug-approach behaviors due to their acquired motivational properties. According to implicit theories of addiction, these stimuli can decrease cognitive control automatically. The present study (n = 49) examined whether reward-associated stimuli can interfere with cognitive processes in the absence of knowledge about stimulus-outcome contingencies. Conditioned stimuli (CS) were paired with high-reward (HR) or low-reward (LR) probabilities of monetary reward using a Pavlovian learning task. Participants were categorized as Aware or Unaware of contingencies using a Bayesian analysis. CS were then used as task-irrelevant distractors in modified flanker and N-back tasks. Results show HR CS can generate increased interference in the flanker task for participants Unaware of contingencies, contributing further evidence for the existence of implicit Pavlovian conditioning. For the N-back task, working memory performance was affected by HR CS, albeit only for Aware participants. These results suggest that CS can interfere implicitly with cognitive processes in a similar way to drug-related stimuli. Such an effect could occur in a stimulus-driven fashion, devoid of top-down goal-directedness. These findings have implications for the conceptualization and study of implicit processes in addiction and highlights the necessity to reconsider the measurement of such phenomena.

Binge drinking is associated with attenuated frontal and parietal activation during successful response inhibition in fearful context.

Binge drinking is associated with increased impulsivity and altered emotional processing. This study investigated, in a group of university students who differed in their level of binge drinking, whether the ability to inhibit a pre-potent response and to delay gratification is disrupted in the presence of emotional context. We further tested whether functional connectivity within intrinsic resting-state networks was associated with alcohol use. Higher incidence of binge drinking was associated with enhanced activation of the lateral occipital cortex, angular gyrus, the left frontal pole during successful response inhibition irrespective of emotional context. This observation suggests a compensatory mechanism. However, higher binge drinking attenuated frontal and parietal activation during successful response inhibition within a fearful context, indicating the selective emotional facilitation of inhibitory control. Similarly, higher binge drinking was associated with attenuated frontopolar activation when choosing a delayed reward over an immediate reward within the fearful, relative to the neutral, context. Resting-state functional data analysis revealed that binge drinking decreased coupling between the right supramarginal gyrus and Ventral Attention Network, indicating alcohol-associated disruption of functional connectivity within brain substrates directing attention. Together, our results suggest that binge drinking makes response inhibition more effortful, yet emotional (more arousing) contexts may mitigate this; disrupted functional connectivity between regions underlying adaptive attentional control, is a likely mechanism underlying these response inhibition effects associated with binge drinking.

How Do Self-Assessment of Alexithymia and Sensitivity to Bodily Sensations Relate to Alcohol Consumption?

BACKGROUND: Alexithymia describes an abnormality of emotional experience that is commonly expressed among individuals with addiction and alcohol abuse disorders. Alexithymic individuals are characterized by difficulties in identifying and describing their emotions. This impairment is linked to the development and maintenance of addiction. Moreover, an emergent theory suggests alexithymia is itself secondary to a failure of interoception (sensitivity to internal bodily signals, including physiological arousal states). METHODS: This study tested for hypothesized contributory roles of alexithymia and dysfunctional interoception in the expression of social drinking. Alexithymia, subjective sensitivity to bodily sensations, and alcohol consumption scores were quantified using the Toronto Alexithymia Scale, the Body Perception Questionnaire, and the Alcohol Use Questionnaire, respectively, in a normative sample (N = 600). Regression and bootstrapping mediation analyses were used to test the hypothesis that alexithymia mediated the association between sensitivity to bodily sensations and alcohol consumption. RESULTS: Alexithymia was positively correlated with sensitivity to bodily sensations and with alcohol consumption. Mediation analysis revealed that alexithymia, and more precisely, difficulty in identifying feelings, mediated the relationship between sensitivity to bodily sensations and alcohol consumption, such that the predictive effect of sensitivity to bodily sensations on alcohol intake became nonsignificant when controlling for alexithymia. CONCLUSIONS: These results indicate that alexithymia is associated with subjective hypersensitivity to bodily sensations. Moreover, our findings support the theoretical proposal that alexithymia is an expression of impaired processing of bodily sensations including physiological arousal, which underpin the development of maladaptive coping strategies, including alcohol use disorders. Our observations extend a growing literature emphasizing the importance of interoception and alexithymia in addiction, which can inform the development of new therapeutic strategies.

Cloninger's Temperament and Character Dimensions of Personality and Binge Drinking Among College Students.

BACKGROUND: Temperament and character dimensions of personality remain largely unexplored in young adults exhibiting binge drinking (BD) patterns. Moreover, the available studies do not consider gender differences and dismiss possible personality heterogeneity among binge drinkers. In this study, we aimed to compare temperament and character dimensions between young binge drinkers and age- and sex-matched social drinkers. We further applied cluster analysis to investigate the potential heterogeneity of personality patterns among BD college students. METHODS: This study included 200 university students of 18 to 24 years of age, who were recruited via an invitation to take an alcohol use survey. These participants included 100 individuals (50 females and 50 males) with a BD pattern, and 100 participants (50 females and 50 males) with a social drinking (SD) pattern. These subjects were evaluated with regard to their use of alcohol and other substances, impulsiveness, sensation seeking, mood, and Cloninger's Temperament and Character Inventory. RESULTS: Between-group comparisons revealed that both male and female binge drinkers were characterized by high levels of novelty seeking, and low levels of persistence and self-directedness. However, cluster analyses within the binge drinker group revealed 2 distinct groups that differed between males and females. These groups shared similarities with Cloninger's type I (high harm-avoidance) and II (high novelty-seeking) alcoholism typology. CONCLUSIONS: The present findings support the subdivision of binge drinkers according to gender and personality dimensions. Male and female binge drinkers should not be considered a unitary group, but rather a population of individuals that encompasses at least 2 distinct personality patterns. These findings have major implications for prevention and treatment approaches.

Altered white matter integrity in whole brain and segments of corpus callosum, in young social drinkers with binge drinking pattern.

Binge drinking is associated with impaired cognitive functioning, but the relationship of cognitive impairments and white matter integrity is less known. We used diffusion tensor imaging (DTI) to investigate the relationships of binge drinking, whole brain white matter integrity and cognitive performance during young adulthood (18 to 25 years), a period of continued brain development in two sessions 1 year apart. Binge drinkers (n = 20) and non-binge drinkers (n = 20) underwent DTI and completed measures of spatial working memory and motor impulsivity. Fractional anisotropy (FA), a measure derived from DTI, was estimated from whole brain and from five segments of the corpus callosum (CC): prefrontal, premotor/supplementary motor, motor, (SMA) sensory and parietal/temporal/occipital (PTO). FA was lower for binge than for non-binge men but not women at Session 1 and 2 for all measurements except for FA in the motor segment, which was significantly increased from Session 1 to Session 2. Lower FA in the prefrontal and PTO CC segments was associated with higher binge score, whereas lower FA in all five segments was associated with greater drug use in men and worse spatial working memory both in men and women. These findings extend the literature by showing that in early adulthood, binge drinking and drug use are linked with degradations in neural white matter and that compromised white matter at this period of brain development is linked with impaired cognitive functioning.

Heightened Impulsivity: Associated with Family History of Alcohol Misuse, and a Consequence of Alcohol Intake.

BACKGROUND: Youths with family history (FH) of alcoholism are at greater risk of developing alcohol use disorder (AUD); heightened impulsive behavior may underlie such increased vulnerability. Here, we studied waiting impulsivity (previously suggested to predispose to alcohol drinking) in young moderate-to-heavy social drinkers (18 to 33 years old) characterized as family history positive (FHP) and negative (FHN) following an alcoholic or nonalcoholic (placebo) drink. METHODS: Two groups of young male and female social drinkers (n = 64) were administered an acute dose of alcohol (0.8 g/kg) or placebo. One group (FHP; n = 24) had first-degree relatives with problems of alcohol misuse; the other group (FHN) did not. Participants completed 4 variants of the Sx-5CSRTT, a task measuring waiting impulsivity. In addition, other types of impulsive behavior were tested (by means of the stop-signal task [SST]; information sampling task [IST]; Delay Discounting Questionnaire; 2-choice impulsivity paradigm; and time estimation task). RESULTS: Young FHP adults showed more premature responding than FHN when evaluated under increased attentional load (high waiting impulsivity), while, in contrast, they presented a more conservative strategy on the IST (less impulsive behavior), compared to FHN. Acute alcohol impaired inhibitory control on the SST in all participants, and induced a marginal increase of premature responses, but did not affect other measures of impulsivity. CONCLUSIONS: Assessing for exaggerated waiting impulsivity may provide a potential endophenotype associated with risk for the development of alcohol addiction (i.e., offspring of alcoholics).

Further evidence of the heterogeneous nature of impulsivity.

'Impulsivity' refers to a range of behaviours including preference for immediate reward (temporal-impulsivity) and the tendency to make premature decisions (reflection-impulsivity) and responses (motor-impulsivity). The current study aimed to examine how different behavioural and self-report measurements of impulsivity can be categorised into distinct subtypes. Exploratory factor analysis using full information maximum likelihood was conducted on 10 behavioural and 1 self-report measure of impulsivity. Four factors of impulsivity were indicated, with Factor 1 having a high loading of the Stop Signal Task, which measures motor-impulsivity, factor 2 representing reflection-impulsivity with loadings of the Information Sampling Task and Matching Familiar Figures Task, factor 3 representing the Immediate Memory Task, and finally factor 4 which represents the Delay Discounting Questionnaire and The Monetary Choice Questionnaire, measurements of temporal-impulsivity. These findings indicated that impulsivity is not a unitary construct, and instead represents a series of independent subtypes. There was evidence of a distinct reflection-impulsivity factor, providing the first factor analysis support for this subtype. There was also support for additional factors of motor- and temporal-impulsivity. The present findings indicated that a number of currently accepted tasks cannot be considered as indexing motor- and temporal-impulsivity suggesting that additional characterisations of impulsivity may be required.

Alpha 2B adrenoceptor genotype moderates effect of reboxetine on negative emotional memory bias in healthy volunteers.

Evidence suggests that emotional memory plays a role in the pathophysiology of depression/anxiety disorders. Noradrenaline crucially modulates emotional memory. Genetic variants involved in noradrenergic signaling contribute to individual differences in emotional memory and vulnerability to psychopathology. A functional deletion polymorphism in the α-2B adrenoceptor gene (ADRA2B) has been linked to emotional memory and post-traumatic stress disorder. The noradrenaline reuptake inhibitor reboxetine attenuates enhanced memory for negative stimuli in healthy and depressed individuals. We examined whether the effect of reboxetine on emotional memory in healthy individuals would be moderated by ADRA2B genotype. ADRA2B deletion carriers demonstrated enhanced emotional memory for negative stimuli compared with deletion noncarriers, consistent with prior studies. Reboxetine attenuated enhanced memory for negative stimuli in deletion noncarriers but had no significant effect in deletion carriers. This is the first demonstration of genetic variation influencing antidepressant drug effects on emotional processing in healthy humans.

Effects of stress and dietary tryptophan enhancement on craving for alcohol in binge and non-binge heavy drinkers.

Stress is known to play an important role in alcohol abuse, whereas binge drinking may increase individuals' susceptibility to the development of alcohol dependence. We set out to investigate whether binge drinkers (BDs) or non-BDs (NBDs) are at a greater risk of an increase in their desire for alcohol following experimental stress induction (modified Trier Social Stress Test; Experiment 1) and to explore the biological mechanisms underlying such an effect (Experiment 2). Preclinical evidence suggests that serotonin may mediate stress-induced reinstatement of alcohol intake. We therefore tested whether dietary tryptophan (TRP) enhancement would modulate stress-induced desire for alcohol and whether it would affect the two populations (BD/NBD) differently. In Experiment 1 (14 NBDs, 10 BDs; mean weekly alcohol intake 50.64 U), stress induction selectively increased strong desire for alcohol compared with the nonstressful condition in BDs. Throughout the experiment, BDs reported greater negative reinforcement type of craving than NBDs, but also a higher expectancy of alcohol-induced negative effects. In Experiment 2, 41 participants (22 NBDs, 19 BDs; mean alcohol intake 38.81 U) were given either the TRP-rich (TRP+; 9 BDs, 11 NBD) or the control (CTR; 10 BD, 11 NBD) diet before undergoing stress induction. In BDs, the TRP+ diet prevented the stress-induced increase in strong desire that was observed in individuals receiving the CTR diet. In NBDs, the TRP+ diet appeared to facilitate an increase in strong desire. These findings suggest that BDs may indeed be at a greater risk than NBDs of an increase in their craving for alcohol when stressed. Furthermore, whereas enhancement of 5-hydroxytryptamine function may moderate the impact of stress on craving in BDs, it seems to facilitate stress-induced craving in NBDs, suggesting that the serotonergic system may be differentially involved depending on individual binge drinking status.

Impaired fear recognition and attentional set-shifting is associated with brain structural changes in alcoholic patients.

Alcoholic patients with multiple detoxifications/relapses show cognitive and emotional deficits. We performed structural magnetic resonance imaging and examined performance on a cognitive flexibility task (intra-extradimensional set shift and reversal; IED). We also presented subjects with fearful, disgust and anger facial emotional expressions. Participants were abstaining, multiply detoxified (MDTx; n = 12) or singly detoxified patients (SDTx; n = 17) and social drinker controls (n = 31). Alcoholic patients were less able than controls to change their behavior in accordance with the changing of the rules in the IED and they were less accurate in recognizing fearful expressions in particular. They also showed lower gray matter volume compared with controls in frontal brain areas, including inferior frontal cortex (IFC) and insula that mediate emotional processing, inferior parietal lobule and medial frontal cortex that mediate attentional and motor planning processes, respectively. Impairments in performance and some of the regional decreases in gray matter were greater in MDTx. Gray matter volume in IFC in patients was negatively correlated with the number of detoxifications, whereas inferior parietal lobule was negatively correlated with the control over drinking score (impaired control over drinking questionnaire). Performance in IED was also negatively correlated with gray matter volume in IFC/BA47, whereas recognition of fearful faces was positively correlated with the IFC gray matter. Repeated episodes of detoxification from alcohol, related to severity of dependency, are coupled with altered brain structure in areas of emotional regulation, attention and motor planning. Such changes may confer increased inability to switch behavior according to environmental demands and social incompetence, contributing to relapse.

Reliable evidence for implicit attentional responses to aversive conditioned stimuli.

Evidence for implicit aversive learning effects has been criticized for its lack of experimental rigor and statistical reliability. Here we examine whether attentional emotional responses to aversive conditioned stimuli can occur in the absence of stimulus-outcome contingency awareness, and use a novel Bayesian tool to reliably perform a post hoc categorization of awareness. Across two experiments (n = 40 and 69) participants completed an aversive conditioning task. A novel Bayesian awareness categorization tool was applied to sensitively measure contingency awareness. Finally, attentional and subjective responses toward conditioned stimuli were measured. For participants unaware of contingencies, conditioned stimuli generated attentional avoidance, but only aware participants showed subjective learning effects. For both experiments, awareness scores for unaware participants did not regress above chance level on a subsequent awareness check, revealing a reliable determination of unawareness states. These findings provide evidence for the existence of aversive learning in the absence of contingency awareness, as demonstrated via conditioned attentional responses, and build an analytical framework that can be extrapolated to other implicit paradigms. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The Continuing Challenges of Studying Parallel Behaviours in Humans and Animal Models.

The use of animal models continues to be essential for carrying out research into clinical phenomena, including addiction. However, the complexity of the clinical condition inevitably means that even the best animal models are inadequate, and this may go some way to account for the apparent failures of discoveries from animal models, including the identification of potential novel therapies, to translate to the clinic. We argue here that it is overambitious and misguided in the first place to attempt to model complex, multifacetted human disorders such as addiction in animals, and especially in rodents, and that all too frequently "validity" of such models is limited to superficial similarities, referred to as "face validity", that reflect quite different underlying phenomena and biological processes from the clinical situation. Instead, a more profitable approach is to identify (a) well-defined intermediate human behavioural phenotypes that reflect defined, limited aspects of, or contributors to, the human clinical disorder, and (b) to develop animal models that are homologous with those discrete human behavioural phenotypes in terms of psychological processes, and underlying neurobiological mechanisms. Examples of past and continuing weaknesses and suggestions for more limited approaches that may allow better homology between the test animal and human condition are made.

'You Can Die With Me But I Won't Let You Live With Me', Exploring Social Influences on the Continuation of Heroin Use in Men Who Use Heroin.

Background: Heroin is a substance with a unique social profile in that it is commonly used by individuals alone but there is a paucity of qualitative research exploring how social influences impact the continuation of heroin use, particularly when people are trying to stop using heroin. This study explored social determinants which influence the continuation of heroin use in males in UK community treatment who use illicit heroin alongside opioid replacement therapy. Design: Participants were self-selecting from an initial purposively recruited sample. Using Janis (1972) 8 symptoms of Groupthink as an a priori framework for analysis, the study method utilised qualitative interviews with fourteen males. The discussions were digitally-recorded, transcribed verbatim, and analysed thematically. Findings: Contrasting with the evidence base, the sample included people who transitioned from recreational drug use to dependent heroin use without experiencing trauma of any kind. Far from becoming socially isolated when actively using heroin, interviews identified a shift in social networks from networks built on shared moments to networks underpinned by transactional exchange. Components of Groupthink were identified when participants described belonging to heroin using networks and continued to use heroin whilst trying to abstain though individual accountability was central to the decision to continue to use heroin. Conclusions: The conflict between the individual goal of abstinence and the group goal of continuation suggests that social network interventions could be more successful if delivered to cohorts of people who buy heroin together.

Alcohol-related cues reduce cognitive control in social drinkers.

Alcohol-related stimuli attract social drinkers' attention (attentional bias). We devised a dual task to test whether attentional biases to alcohol-related stimuli are modulated by cognitive control mechanisms. Sixteen nondependent healthy social drinkers were required to respond to the direction of a central arrow (target) and to ignore adjacent congruent (low cognitive load) or incongruent (high cognitive load) distracting arrows (flankers) in the presence of alcohol-related, neutral or plain grey backgrounds. Percentages of correct responses to the target and reaction time of correct responses (latency) were recorded. The difference score of the flanker effect (latency incongruent-latency congruent) between trials when backgrounds were alcohol-related relative to when they were neutral was also computed. Latencies increased in the presence of the alcohol-related images relative to both the neutral and the grey displays, but only under high cognitive load. Response accuracy did not show this significant difference. The flanker effect difference score correlated positively with the participants' average weekly alcohol intake. The data suggest that the presence of alcohol-associated stimuli attenuates cognitive control processes in social drinkers, an effect that was associated with the participants' average weekly alcohol intake.

Alcohol increases hypnotic susceptibility.

One approach to hypnosis suggests that for hypnotic experience to occur frontal lobe activity must be attenuated. For example, cold control theory posits that a lack of awareness of intentions is responsible for the experience of involuntariness and/or the subjective reality of hypnotic suggestions. The mid-dorso-lateral prefrontal cortex and the ACC are candidate regions for such awareness. Alcohol impairs frontal lobe executive function. This study examined whether alcohol affects hypnotisability. We administered 0.8 mg/kg of alcohol or a placebo to 32 medium susceptible participants. They were subsequently hypnotised and given hypnotic suggestions. All participants believed they had received some alcohol. Participants in the alcohol condition were more susceptible to hypnotic suggestions than participants in the placebo condition. Impaired frontal lobe activity facilitates hypnotic responding, which supports theories postulating that attenuation of executive function facilitates hypnotic response, and contradicts theories postulating that hypnotic response involves enhanced inhibitory, attentional or other executive function.

A parsimonious, integrative model of key psychological correlates of UK university students' alcohol consumption.

AIMS: To examine the predictive utility of psychological correlates of alcohol consumption identified in previous (US-dominated) research for a UK student sample and construct an integrative model predictive of alcohol dependency in a sample of first-year undergraduate students. METHODS: A self-report questionnaire completed by 230 students measured stable and modifiable correlates of alcohol dependence. Stable correlates included age when first regularly drinking (age of onset), personality traits and religiosity. Modifiable measures included drinking motives, self-efficacy, alcohol-related expectancies, prototype perceptions and normative beliefs. RESULTS: The final multivariate model highlighted the importance of age of onset, sensation-seeking and a series of social cognitive measures including: social drinking motives, confidence in the ability to drink within government guidelines (self-efficacy) and the perceived quantity and frequency of alcohol consumed by university friends. Beta-coefficients indicated that self-efficacy and social drinking motives were particularly important predictors. A significant interaction was observed between age of onset and self-efficacy. Earlier onset was associated with higher levels of alcohol dependence for low and moderate, but not high levels of self-efficacy. CONCLUSION: The model presented here could be used to identify students at risk of alcohol dependence and inform the design of campus-based interventions.

Can intranasal oxytocin reduce craving in automated addictive behaviours? A systematic review.

Existing pharmacotherapies for managing craving, a strong predictor of relapse to automated addictive behaviours, are limited in efficacy and characterised by increased health risks associated with their pharmacological profile. Preclinical studies have identified oxytocin as a promising pharmacotherapy with anticraving properties for addictive behaviours. Here, we provide the first systematic review of 17 human studies (n = 722; 30% female) investigating the efficacy of intranasal oxytocin to reduce craving or consumption in addictive behaviours. We identify intranasal oxytocin as a method that warrants further investigation regarding its capacity to decrease cue-induced, acute stress-induced or withdrawal-related craving and relapse related to alcohol, cannabis, opioids, cocaine or nicotine, including a potential role as ad hoc medication following exposure to drug-related cues. Future studies should investigate the role of factors such as treatment regimens and sample characteristics, including the role of the amygdala, which we propose as a distinct mechanism mediating oxytocin's anticraving properties.

Emotional processes in binge drinking: A systematic review and perspective.

Binge drinking is a widespread alcohol consumption pattern commonly engaged by youth. Here, we present the first systematic review of emotional processes in relation to binge drinking. Capitalizing on a theoretical model describing three emotional processing steps (emotional appraisal/identification, emotional response, emotional regulation) and following PRISMA guidelines, we considered all identified human studies exploring emotional abilities among binge drinkers. A literature search was conducted in PubMed, Scopus, and PsychINFO, and a standardized methodological quality assessment was performed for each study. The main findings offered by the 43 studies included are: 1) regarding emotional appraisal/identification, binge drinking is related to heightened negative emotional states, including greater severity of depressive and anxiety symptoms, and have difficulties in recognizing emotional cues expressed by others; 2) regarding emotional response, binge drinkers exhibit diminished emotional response compared with non-binge drinkers; 3) regarding emotional regulation, no experimental data currently support impaired emotion regulation in binge drinking. Variability in the identification and measurement of binge drinking habits across studies limits conclusions. Nevertheless, current findings establish the relevance of emotional processes in binge drinking and set the stage for new research perspectives to identify the nature and extent of emotional impairments in the onset and maintenance of excessive alcohol use.

Interoceptive cardiac signals selectively enhance fear memories.

Fear is coupled to states of physiological arousal. We tested how learning and memory of threat, specifically conditioned fear, is influenced by interoceptive signals. Forty healthy individuals were exposed to two threat (conditioned stimuli [CS+], paired with electrocutaneous shocks) and two safety (CS-) stimuli, time-locked to either cardiac ventricular systole (when arterial baroreceptors signal cardiovascular arousal to brainstem), or diastole (when these afferent signals are quiescent). Threat learning was indexed objectively using skin conductance responses (SCRs). During acquisition of threat contingencies, cardiac effects dominated: Stimuli (both CS+ and CS-) presented at systole evoked greater SCR responses, relative to stimuli (both CS+ and CS-) presented at diastole. This difference was amplified in more anxious individuals. Learning of conditioned fear was established by the end of the acquisition phase, which was followed by an extinction phase when unpaired CSs were presented at either the same or switched cardiac contingencies. One day later, electrocutaneous shocks triggered the reinstatement of fear responses. Subsequent presentation of stimuli previously encoded at systole evoked higher SCRs. Moreover, only those participants for whom stimuli had the same cardiac-contingency over both acquisition and extinction phases retained conditioned fear memory (i.e., CS+ > CS-). Our findings reveal two important cardiac afferent effects on threat learning and memory: 1) Cardiac signals bias processing toward threat; and 2) cardiac signals are a context for fear memory; altering this context can disrupt the memory. These observations suggest how threat reactivity may be reinforced and maintained by both acute and enduring states of cardiac arousal. (PsycInfo Database Record (c) 2021 APA, all rights reserved).