Differential Skin Conductance Responses Research Articles

Intolerance of Uncertainty is Associated with Heightened Arousal During Extinction Learning and Retention: Preliminary Evidence from a Clinical Sample with Anxiety and Obsessive-Compulsive Disorders

Abstract Background Uncertainty-related distress is considered a hallmark of anxiety and obsessive compulsive disorders (OCD). Previous research in community samples has demonstrated that individuals with high Intolerance of Uncertainty (IU), the tendency to find uncertainty aversive, display altered threat extinction learning and retention. Methods Here, we conducted an exploratory secondary analysis of an existing dataset (Steinman et al., 2022) to examine the extent to which IU in a clinical sample with anxiety and OCD predicts threat extinction learning and retention. Participants with an anxiety disorder and/or OCD completed a differential threat learning task across two days (n = 27). Skin conductance response (SCR) was used as an index of conditioned responding. Results No significant effects of self-reported IU were observed for differential SCR during any of the experimental phases. However, higher self-reported IU, while controlling for trait anxiety, was specifically associated with greater SCR overall during same-day extinction training, next-day extinction training, and next-day reinstatement test. Conclusions Such findings provide preliminary evidence that higher IU within clinical samples with anxiety and/or OCD may be associated with heightened arousal under uncertainty, and highlight IU as a promising treatment target for anxiety and OCD.

Good moments to stimulate the brain – A randomized controlled double-blinded study on anodal transcranial direct current stimulation of the ventromedial prefrontal cortex on two different time points in a two-day fear conditioning paradigm

It is assumed that extinction learning is a suitable model for understanding the mechanisms underlying exposure therapy. Furthermore, there is evidence that non-invasive brain stimulation (NIBS) can elevate extinction learning by enhancing frontal brain activity and therefore NIBS can augment symptom reduction during exposure therapy in phobias. But, the underlying processes are still not well established. Open questions arise from NIBS time points and electrode placement, among others. Therefore, we investigated in a 2-day fear conditioning experiment, whether anodal transcranial direct current stimulation (tDCS) of the ventromedial prefrontal cortex (vmPFC) modulates either fear memory consolidation or dampened fear reaction during fear extinction. Sixty-six healthy participants were randomly assigned either to a group that received tDCS after fear acquisition (and before fear memory consolidation), to a group that received tDCS directly before fear extinction, or to a control group that never received active stimulation (sham). Differential skin conductance response (SCR) to CS+ vs. CS- was significantly decreased in both tDCS-groups compared to sham group. Our region of interest, the vmPFC, was stimulated best focally with a lateral anode position and a cathode on the contralateral side. But this comes along with a slightly lateral stimulation of vmPFC depending on whether anode is placed left or right. To avoid unintended effects of stimulated sides the two electrode montages (anode left or right) were mirror-inverted which led to differential effects in SCR and electrocortical (mainly late positive potential [LPP]) data in our exploratory analyses. Results indicated that tDCS-timing is relevant for fear reactions via disturbed fear memory consolidation as well as fear expression, and this depends on whether vmPFC is stimulated with either left- or right-sided anode electrode montage. Electrocortical data can shed more light on the underlying neural correlates and exaggerated LPP seems to be associated with disturbed fear memory consolidation and dampened SCR to CS+ vs. CS-, but solely in the right anode electrode montage. Further open questions addressing where and when to stimulate the prefrontal brain in the course of augmenting fear extinction are raised.

Incidental learning of faces during threat: No evidence for enhanced physiological responses to former threat identities

Remembering an unfamiliar person and the contextual conditions of that encounter is important for adaptive future behavior, especially in a potentially dangerous situation. Initiating defensive behavior in the presence of former dangerous circumstances can be crucial. Recent studies showed selective electrocortical processing of faces that were previously seen in a threat context compared to a safety context, however, this was not reflected in conscious recognition performance. Here, we investigated whether previously seen threat-faces, that could not be remembered, were capable to activate defensive psychophysiological response systems. During an encoding phase, 50 participants with low to moderate levels of anxiety viewed 40 face pictures with neutral expressions (6 s each), without an explicit learning instruction (incidental learning task). Each half of the faces were presented with contextual background colors that signaled either threat-of-shock or safety. In the recognition phase, all old and additional new faces (total of 60) were presented intermixed without context information. Participants had to decide whether a face was new or had been presented previously in a threatening or a safe context. Results show moderate face recognition independent of context conditions. Startle reflex and skin conductance responses (SCR) were more pronounced for threat compared to safety during encoding. For SCR, this differentiation was enhanced with higher levels of depression and anxiety. There were no differential startle reflex or SCR effects during recognition. From a clinical perspective, these findings do not support the notion that perceptual biases and physiological arousal directly relate to threat-associated identity recognition deficits in healthy and clinical participants with anxiety and trauma-related disorders.

The impact of physical exercise on the consolidation of fear extinction memories.

Based on the mechanisms of fear extinction, exposure therapy is the most common treatment for anxiety disorders. However, extinguished fear responses can reemerge even after successful treatment. Novel interventions enhancing exposure therapy efficacy are therefore critically needed. Physical exercise improves learning and memory and was also shown to enhance extinction processes. This study tested whether physical exercise following fear extinction training improves the consolidation of extinction memories. Sixty healthy men underwent a differential fearconditioning paradigm with fear acquisition training on day 1 and fear extinction training followed by an exercise or resting control intervention on day 2. On day 3, retrieval and reinstatement were tested including two additional but perceptually similar stimuli to explore the generalization of exercise effects. Exercise significantly increased heart rate, salivary alpha amylase, and cortisol, indicating successful exercise manipulation. Contrary to our expectations, exercise did not enhance but rather impaired extinction memory retrieval on the next day, evidenced by significantly stronger differential skin conductance responses (SCRs) and pupil dilation (PD). Importantly, although conditioned fear responses were successfully acquired, they did not fully extinguish, explaining why exercise might have boosted the consolidation of the original fear memory trace instead. Additionally, stronger differential SCRs and PD toward the novel stimuli suggest that the memory enhancing effects of exercise also generalized to perceptually similar stimuli. Together, these findings indicate that physical exercise can facilitate both the long-term retrievability and generalization of extinction memories, but presumably only when extinction was successful in the first place.

Approximating exposure therapy in the lab: Replacing the CS+ with a similar versus a different stimulus and including additional stimuli resembling the CS+ during extinction

Recent studies have shown that extinction training including the conditional stimulus (CS+) and stimuli that are similar to the CS + enhances extinction retention and generalisation to novel stimuli. However, in a clinical setting, the CS+ is rarely available for use during exposure therapy. The aim of the present study was to determine if replacing the CS+ with a similar versus different stimulus, and including other similar stimuli during extinction, could reduce fear at test on par with extinction using the original CS+ with and without other similar stimuli. In an experiment conducted in a single session, participants completed a habituation phase followed by an acquisition phase using two dog images presented with (CS+) and without (CS-) an acoustic unconditional stimulus (US). Participants were randomly allocated to four extinction conditions: similar CS + dog with novel dog images (Similar replacement extinction condition); different CS + dog with novel dog images (Different replacement extinction condition); original CS + dog with novel dog images (Multiple extinction control condition); and original CS + without novel dog images (Standard extinction control condition). All participants completed a test phase with the original CSs followed by a generalisation test with another two novel dog images. All groups acquired, and then extinguished differential skin conductance responses (SCRs) with no differences observed between groups. Whereas the Similar replacement extinction group and the Multiple and Standard extinction control groups did not exhibit significant differential SCRs when re-exposed to the original CS + relative to the CS- at test, differential responding to the CSs was significant at test in the Different replacement extinction group. There were no significant differences between groups in SCRs to the two novel dog images during the generalisation phase and in between-phase subjective ratings. Findings suggest that replacement stimuli used during extinction should be as similar as possible to the CS + to reduce physiological arousal to the original CS+.

Using pre-treatment de novo threat conditioning outcomes to predict treatment response to DCS augmentation of exposure-based CBT

BackgroundOver a decade and a half of research has resulted in inconsistent evidence for the efficacy of d-cycloserine (DCS), a partial glutamatergic N-methyl-D-aspartate agonist, for augmenting exposure-based cognitive behavioral therapy (CBT) for anxiety- and fear-based disorders. These variable findings have motivated the search for moderators of DCS augmentation efficacy. MethodsIn this secondary analysis of a previous randomized clinical trial, we evaluated the value of de novo threat conditioning outcomes—degree of threat acquisition, extinction, and extinction retention—for predicting treatment response to exposure-based CBT for social anxiety disorder, applied with and without DCS augmentation in a sample of 59 outpatients. ResultsWe found that average differential skin conductance response (SCR) during extinction and extinction retention significantly moderated the prediction of clinical response to DCS: participants with poorer extinction and extinction retention showed relatively improved treatment response with DCS. No such effects were found for expectancy ratings, consistent with accounts of DCS selectively aiding lower-order but not higher-order extinction learning. ConclusionsThese findings provide support for extinction and extinction retention outcomes from threat conditioning as potential pre-treatment biomarkers for DCS augmentation benefits. Independent of DCS augmentation, the current study did not support threat conditioning outcomes as useful for predicting response to exposure-based CBT.

Manipulating expectancy violations to strengthen the efficacy of human fear extinction

Recent theoretical and clinical articles have emphasized a role for expectancy violations in improving the effectiveness of exposure therapy. Expectancy violations are critical to extinction learning and strengthening these violations has been suggested to improve the formation and retention of extinction memories, which should result in lasting symptom reductions after treatment. However, more detailed mechanistic insights in this process are needed to better inform clinical interventions. In two separate fear-conditioning experiments, we investigated whether stronger expectancy violations (Exp1) or fostering awareness of expectancy violations (Exp2) during extinction could reduce the subsequent return of fear. We measured fear potentiated startle (FPS) and skin conductance responses (SCR) as physiological indices of fear, and US expectancy ratings to assess our manipulations. While we successfully created stronger expectancy violations in Exp1, we found no evidence that these stronger violations reduced the return of fear at test. Interestingly, fostering awareness of violations (Exp2) reduced differential SCRs, but not FPS responses. These findings provide novel insights into the effect of US expectancies on fear extinction in the lab, but they also illustrate the complexity of capturing clinically relevant processes of change with fear-conditioning studies.

Threat reversal learning and avoidance habits in generalised anxiety disorder

Avoidance and heightened responses to perceived threats are key features of anxiety disorders. These disorders are characterised by inflexibility in dynamically updating behavioural and physiological responses to aversively conditioned cues or environmental contexts which are no longer objectively threatening, often manifesting in perseverative avoidance. However, less is known about how anxiety disorders might differ in adjusting to threat and safety shifts in the environment or how idiosyncratic avoidance responses are learned and persist. Twenty-eight patients with generalised anxiety disorder (GAD), without DSM co-morbidities, and 27 matched healthy controls were administered two previously established paradigms: Pavlovian threat reversal and shock avoidance habits through overtraining (assessed following devaluation with measures of perseverative responding). For both tasks we used subjective report scales and skin conductance responses (SCR). In the Pavlovian threat reversal task, patients with GAD showed a significantly overall higher SCR as well as a reduced differential SCR response compared to controls in the early but not late reversal phase. During the test of habitual avoidance responding, GAD patients did not differ from controls in task performance, habitual active avoidance responses during devaluation, or corresponding SCR during trials, but showed a trend toward more abstract confirmatory subjective justifications for continued avoidance following the task. GAD patients exhibited significantly greater skin conductance responses to signals of threat than controls, but did not exhibit the major deficits in reversal and safety signal learning shown previously by patients with OCD. Moreover, this patient group, again unlike OCD patients, did not show evidence of altered active avoidance learning or enhanced instrumental avoidance habits. Overall, these findings indicate no deficits in instrumental active avoidance or persistent avoidance habits, despite enhanced responses to Pavlovian threat cues in GAD. They suggest that GAD is characterised by passive, and not excessively rigid, avoidance styles.

Skin conductance levels and responses in Asian and White participants during fear conditioning✰

Fear conditioning paradigms are frequently used in the translational study of anxiety and fear-related disorders. Accordingly, it is important to understand whether the measurement of fear conditioning responses is systematically influenced by an individual's race. Studies have found increased pain sensitivity and smaller physiological startle responses in Asian individuals, compared to White individuals; to our knowledge, no studies have evaluated whether skin conductance response (SCR) outcomes differ between Asian and White individuals. In a series of secondary data analyses, we investigated potential differences in skin conductance level (SCL), orienting SCR, unconditioned SCR, SCR to CS+ and CS-, differential SCR, and differential SCR non-responder status. In sample 1, Asian participants (n = 97) demonstrated a significantly smaller mean differential SCR compared to White participants (n = 86). No other between group differences were observed. In sample 2, there was no difference in mean differential SCR between Asian (n = 52) and White (n = 62) participants, although more Asian participants failed to show adequate skin conductance levels for study entry. To our knowledge, this is the first study to evaluate differences between Asian and White samples using skin conductance outcomes in a fear conditioning paradigm. We detected only subtle evidence for SCR differences between Asian and White samples, unlikely to reach significance outside large studies.

Threat Responsivity Predicts Posttraumatic Stress Disorder Hyperarousal Symptoms in Children after Hurricane Florence.

Following a traumatic event, posttraumatic stress disorder (PTSD) symptoms are common. Considerable research has identified a relationship between physiological responses during fear learning and PTSD. Adults with PTSD display atypical physiological responses, such as increased skin conductance responses (SCR) to threatening cues during fear learning (Orr et al., 2000). However, little research has examined these responses in childhood when fear learning first emerges. We hypothesized that greater threat responsivity in early acquisition during fear conditioning before Hurricane Florence would predict PTSD symptoms in a sample of young children following the hurricane. The final sample included 58 children in North Carolina who completed fear learning before Hurricane Florence—a potentially traumatic event. After the hurricane, we assessed severity of hurricane impact and PTSD symptoms. We found that threat responsivity as measured by differential SCR during fear learning before the hurricane predicted PTSD hyperarousal symptoms and that hurricane impact predicted PTSD symptoms following the disaster. This exploratory work suggests that prospective associations between threat responsivity and PTSD symptoms observed in adulthood may be replicated in early childhood. Results are discussed in the context of the current COVID-19 crisis.

Conditioned physiological reactivity and PTSD symptoms across the menstrual cycle: Anxiety sensitivity as a moderator.

Posttraumatic stress disorder (PTSD) is often associated with heightened physiological reactivity during fear conditioning procedures, but results vary across studies. This study examined whether anxiety sensitivity (AS), or the fear of arousal-related sensations, strengthens the relationship between PTSD symptoms and skin conductance responses (SCR) during fear conditioning and extinction. Because gonadal hormones implicated in fear learning fluctuate across the menstrual cycle, the stability of these relationships in women was examined in 2 distinct menstrual cycle phases. Thirty-two trauma-exposed women, half of whom had PTSD, completed the Clinician-Administered PTSD Scale, Anxiety Sensitivity Inventory, and a fear conditioning and extinction paradigm during the midluteal (mLP) and early-follicular (eFP) menstrual cycle phases. In the mLP, stronger SCR to stimuli paired with shock (CS +) during fear acquisition significantly predicted greater PTSD symptoms only when AS was high and after removing an outlier. This appeared driven by effects on Numbing and Hyperarousal symptom clusters. Other hypothesized interactions between AS and CS responses were not significant. However, in the eFP, differential SCR between the CS + and CS- during extinction predicted significantly greater PTSD symptoms, and there was a trend for this effect being stronger as AS increased. Results offer preliminary evidence that high AS contributes to a stronger relationship between SCR during fear acquisition and PTSD symptoms, at least among women in the mLP. Further research investigating the impact of individual differences in traits such as AS on the relationship between conditioned fear responses and PTSD symptoms is warranted. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Potentiated perceptual neural responses to learned threat during Pavlovian fear acquisition and extinction in adolescents.

Adolescents' experience of heightened anxiety and increased vulnerability to develop anxiety disorders is believed to partly result from blunted fear extinction processes. However, whether this anxiety is mediated by adolescent-specific differences in perceptual responses to learned threat is not known. To investigate this, we used EEG to examine reinforcement-dependent changes in early visual event-related potentials in adolescents (N=28, 13-14 years) and adults (N=23, 25-26 years old) during a differential Pavlovian fear conditioning task, with one conditioned stimulus (CS+) paired with an aversive sound (unconditioned stimulus [US]) on 50% of trials, and another (CS-) never paired with the US. An immediate extinction phase followed, where both CSs were presented alone. We found age-dependent dissociations between explicit and implicit measures of fear learning. Specifically, both adolescents and adults demonstrated successful fear conditioning and extinction according to their explicit awareness of changes in CS contingencies and their evaluative CS ratings, and their differential skin conductance responses. However, for the first time we show age differences at the neural level in perceptual areas. Only adolescents showed greater visual P1 and N1 responses to the CS+ compared to the CS- during acquisition, a dissociation that for the N1 was maintained during extinction. We suggest that the adolescent perceptual hyper-responsivity to learned threat and blunted extinction reported here could be an adaptive mechanism to protect adolescents from harm. However, this hyper-responsivity may also confer greater vulnerability to experience pathological levels of anxiety at this developmental stage.

Does the assessment of different combinations of within-phase subjective measures influence electrodermal responding and between-phase subjective ratings during fear conditioning and extinction experiments?

The type and number of dependent measures assessed have varied between fear conditioning and extinction experiments and it remains unclear whether methodological differences influence results. Measuring skin conductance responses (SCRs) and between-phase subjective ratings between four conditions; Con condition had no within-phase ratings; US Exp condition included within-phase US expectancy ratings only; CS Eval condition included within-phase CS evaluations only and All Meas condition included both. All Meas condition exhibited larger SCRs compared to other conditions during acquisition, extinction, and return of differential responding at test. Differential SCRs did not extinguish in CS Eval and Con conditions, and CS Eval condition exhibited smaller CS- SCRs than other conditions throughout phases. US Exp condition revealed differential conditioning, successful extinction, and no return of differential SCRs. Between-phase ratings were not affected by within-phase ratings. Researchers should consider assessing different combinations of within-phase subjective ratings depending on the aims of their research.

Revisiting potential associations between brain morphology, fear acquisition and extinction through new data and a literature review

Inter-individual differences in defensive responding are widely established but their morphological correlates in humans have not been investigated exhaustively. Previous studies reported associations with cortical thickness of the dorsal anterior cingulate cortex, insula and medial orbitofrontal cortex as well as amygdala volume in fear conditioning studies. However, these associations are partly inconsistent and often derived from small samples. The current study aimed to replicate previously reported associations between physiological and subjective measures of fear acquisition and extinction and brain morphology. Structural magnetic resonance imaging was performed on 107 healthy adults who completed a differential cued fear conditioning paradigm with 24 h delayed extinction while skin conductance response (SCR) and fear ratings were recorded. Cortical thickness and subcortical volume were obtained using the software Freesurfer. Results obtained by traditional null hypothesis significance testing and Bayesians statistics do not support structural brain-behavior relationships: Neither differential SCR nor fear ratings during fear acquisition or extinction training could be predicted by cortical thickness or subcortical volume in regions previously reported. In summary, the current pre-registered study does not corroborate associations between brain morphology and inter-individual differences in defensive responding but differences in experimental design and analyses approaches compared to previous work should be acknowledged.

Effects of intranasal insulin as an enhancer of fear extinction: a randomized, double-blind, placebo-controlled experimental study.

Fear-extinction based psychotherapy (exposure) is the most effective method for treating anxiety disorders. Notwithstanding, since some patients show impairments in the unlearning of fear and insufficient fear remission, there is a growing interest in using cognitive enhancers as adjuvants to exposure. As insulin plays a critical role in stress processes and acts as a memory enhancer, this study aimed to assess the capacity of intranasal insulin to augment fear extinction. A double-blind, placebo-controlled differential fear-conditioning paradigm was conducted in 123 healthy participants (63 females). Pictures of faces with neutral expressions were used as conditioned stimuli and electric shocks as unconditioned stimuli. The paradigm consisted of four phases presented on three consecutive days: acquisition (day 1), extinction (day 2), reinstatement and re-extinction (day 3). A single intranasal dose of insulin (160 IU) or placebo was applied on day 2, 45 min before fear extinction. Skin conductance response (SCR), fear-potentiated startle (FPS) and expectancy ratings were assessed. During extinction, the insulin group (independent of sex) showed a significantly stronger decrease in differential FPS in comparison with the placebo group. Furthermore, a sex-specific effect was found for SCR, with women in the insulin group showing a greater decrease of differential SCR both at early extinction and at late re-extinction. Our results provide first evidence that intranasal insulin facilitates fear extinction processes and is therefore a promising adjuvant for extinction-based therapies in anxiety and related disorders. Sex-specific effects should be taken into consideration in future studies.

Influence of intranasal oxytocin on fear consolidation in healthy humans

BackgroundAlthough recent data in healthy humans suggestthat treatment with intranasal oxytocin (OT) may facilitate extinction recall,to date, little is known about the effects of OT on memory consolidationprocesses.AimTo examine the...

Fear conditioning and extinction in alcohol dependence: Evidence for abnormal amygdala reactivity.

Fear conditioning and extinction (FCE) are vital processes in adaptive emotion regulation and disrupted in anxiety disorders. Despite substantial comorbidity between alcohol dependence (ALC) and anxiety disorders and reports of altered negative emotion processing in ALC, neural correlates of FCE in this clinical population remain unknown. Here, we used a 2-day fear learning paradigm in 43 healthy participants and 43 individuals with ALC at the National Institutes of Health. Main outcomes of this multimodal study included structural and functional brain magnetic resonance imaging, clinical measures, as well as skin conductance responses (SCRs) to confirm differential conditioning. Successful FCE was demonstrated across participants by differential SCRs in the conditioning phase and no difference in SCRs to the conditioned stimuli in the extinction phase. The ALC group showed significantly reduced blood oxygenation level-dependent responses in the right amygdala during conditioning (Cohen's d = .89, P(FWE) = .037) and in the left amygdala during fear renewal (Cohen's d = .68, P(FWE) = .039). Right amygdala activation during conditioning was significantly correlated with ALC severity (r = .39, P(Bonferroni) = .009), depressive symptoms (r = .37, P(Bonferroni) = .015), trait anxiety (r = .41, P(Bonferroni) = .006), and perceived stress (r = .45, P(Bonferroni) = .002). Our data suggest that individuals with ALC have dysregulated fear learning, in particular, dysregulated neural activation patterns, in the amygdala. Furthermore, amygdala activation during fear conditioning was associated with ALC-related clinical measures. The FCE paradigm may be a promising tool to investigate structures involved in negative affect regulation, which might inform the development of novel treatment approaches for ALC.

The role of hippocampal spatial representations in contextualization and generalization of fear

Using contextual information to predict aversive events is a critical ability that protects from generalizing fear responses to safe contexts. Animal models have demonstrated the importance of spatial context representations within the hippocampal formation in contextualization of fear learning. The ventromedial prefrontal cortex (vmPFC) is known to play an important role in safety learning, possibly also through the incorporation of context information. However, if contextual representations are related to context-dependent expression of fear memory in humans remains unclear. Twenty-one healthy participants underwent functional MRI combined with a cue-context conditioning paradigm within a self-navigated virtual reality environment. The environment included two buildings (Threat and Safe context), which had distinct features outside but were identical inside. Within each context, participants saw two cues (CS+, CS-). The CS+ was consistently (100% reinforcement rate) paired with an electric shock in the Threat context, but never in the Safe context. The CS- was never paired with a shock. We found robust differential skin conductance responses (SCRs; CS+ ​> ​CS-) in the Threat context, but also within the Safe context, indicating fear generalization. Within the Safe context, vmPFC responses to the CS+ were larger than those in the Threat context. We furthermore found environment-specific representations for the two contexts in the training paradigm (i.e., before conditioning took place) in the hippocampus to be related to fear expression and generalization. Namely, participants with a weak context representation (z-score < 1.65) showed stronger fear generalization compared to participants with a strong context representation (z-score > 1.65). Thus, a weak neural representation strength of spatial context may explain overgeneralization of memory to safe contexts. In addition, our findings demonstrate that context-dependent regulation of fear expression engages ventromedial prefrontal pathways suggesting this involves a similar mechanism that is known to be involved in retrieval of extinction memory.

L-DOPA improves extinction memory retrieval after successful fear extinction

RationaleA promising strategy to prevent a return of fear after exposure-based therapy in anxiety disorders is to pharmacologically enhance the extinction memory consolidation presumed to occur after exposure. Accumulating evidence suggests that the effect of a number of pharmacological consolidation enhancers depends on a successful fear reduction during exposure. Here, we employed the dopamine precursor L-DOPA to clarify whether its documented potential to enhance extinction memory consolidation is dependent on successful fear extinction.MethodsIn two double-blind, randomized and placebo-controlled experiments (experiment 1: N = 79, experiment 2: N = 32) comprising fear conditioning (day 1), extinction followed by administration of 150 mg L-DOPA or placebo (day 2) and a memory test (day 3) in healthy male adults, conditioned responses were assessed as differential skin conductance responses. We tested whether the effect of L-DOPA on conditioned responses at test depended on conditioned responses at the end of extinction in an experiment with a short (10 trials, experiment 1) and long (25 trials, experiment 2) extinction session.ResultsIn both experiments, the effect of L-DOPA was dependent on conditioned responses at the end of extinction. That is, post-extinction L-DOPA compared to placebo administration reduced conditioned responses at test only in participants showing a complete reduction of conditioned fear at the end of extinction.ConclusionThe results support the potential use of L-DOPA as a pharmacological adjunct to exposure treatment, but point towards a common boundary condition for pharmacological consolidation enhancers: a successful reduction of fear in the exposure session.

Differential Associations of Deprivation and Threat With Cognitive Control and Fear Conditioning in Early Childhood.

Early-life adversity (ELA) is strongly associated with risk for psychopathology. Within adversity, deprivation, and threat may lead to psychopathology through different intermediary pathways. Specifically, deprivation, defined as the absence of expected cognitive and social inputs, is associated with lower performance on complex cognitive tasks whereas threatening experiences, defined as the presence of experiences that reflect harm to the child, are associated with atypical fear learning and emotional processes. However, distinct associations of deprivation and threat on behavioral outcomes have not been examined in early childhood. The present study examines how deprivation and threat are associated with cognitive and emotional outcomes in early childhood. Children 4–7 years old completed behavioral tasks assessing cognitive control (N = 58) and fear conditioning (N = 45); deprivation and threat were assessed using child interview and parent questionnaires. Regression analyses were performed including deprivation and threat scores and controls for age, gender, and IQ. Because this is the first time these variables have been examined in early childhood, interactions with age were also examined. Deprivation, but not threat was associated with worse performance on the cognitive control task. Threat, but not deprivation interacted with age to predict fear learning. Young children who experienced high levels of threat showed evidence of fear learning measured by differential skin conductance response even at the earliest age measured. In contrast, for children not exposed to threat, fear learning emerged only in older ages. Children who experienced higher levels of threat also showed blunted reactivity measured by amplitude of skin conductance response to the reinforced stimuli regardless of age. Results suggest differential influences of deprivation and threat on cognitive and emotional outcomes even in early childhood. Future work should examine the neural mechanisms underlying these behavioral changes and link changes with increased risk for negative outcomes associated with adversity exposure, such as psychopathology.