Emotional State Transitions in Trauma-Exposed Individuals With and Without Posttraumatic Stress Disorder.

Importance: Posttraumatic stress disorder (PTSD) is marked by the contrasting symptoms of hyperemotional reactivity and emotional numbing (ie, reduced emotional reactivity). Comprehending the mechanism that governs the transition between neutral and negative emotional states is crucial for developing targeted therapeutic strategies. Objectives: To explore whether individuals with PTSD experience a more pronounced shift between neutral and negative emotional states and how the intensity of emotional numbing symptoms impacts this shift. Design, Setting, and Participants: This cross-sectional study used hierarchical bayesian modeling to fit a 5-parameter logistic regression to analyze the valence ratings of images. The aim was to compare the curve's slope between groups and explore its association with the severity of emotional numbing symptoms. The study was conducted online, using 35 images with a valence range from highly negative to neutral. The rating of these images was used to assess the emotional responses of the participants. The study recruited trauma-exposed individuals (witnessed or experienced life-threatening incident, violent assault, or someone being killed) between January 17 and March 8, 2023. Participants completed the PTSD Checklist for the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-5) (PCL-5). Exposure: On the basis of DSM-5 criteria (endorsing at least 1 symptom from clusters B and C and 2 from D and E), participants were categorized as having probable PTSD (pPTSD) or as trauma-exposed controls (TECs). Main Outcomes and Measures: The main outcome was the slope parameter (b) of the logistic curve fitted to the valence rating. The slope parameter indicates the rate at which emotional response intensity changes with stimulus valence, reflecting how quickly the transition occurs between neutral and negatively valenced states. The secondary outcome was the association between emotional numbing (PCL-5 items 12-14) and the slope parameter. Results: A total of 1440 trauma-exposed individuals were included. The pPTSD group (n = 445) was younger (mean [SD] age, 36.1 [10.9] years) compared with the TEC group (mean [SD] age, 41.5 [13.3] years; P < .001). Sex distribution (427 women in the TEC group vs 230 in the pPTSD group) did not significantly differ between groups (P = .67). The pPTSD group exhibited a steeper slope (mean slope difference, -0.255; 89% highest posterior density [HPD], -0.340 to -0.171) compared with the controls. Across all individuals (n = 1440), a robust association was found between the slope and emotional numbing severity (mean [SD] additive value, 0.100 [0.031]; 89% HPD, 0.051-0.15). Additional analysis controlling for age confirmed the association between emotional numbing and transition sharpness (mean [SD] additive value, 0.108 [0.032]; 89% HPD, 0.056-0.159), without evidence of an age-related association (mean [SD] additive value, 0.031 [0.033]; 89% HPD, -0.022 to 0.083). Conclusions and Relevance: These findings support that individuals with PTSD undergo rapid transitions between neutral and negative emotional states, a phenomenon intensified by the severity of emotional numbing symptoms. Therapeutic interventions aimed at moderating these swift emotional transitions could potentially alleviate PTSD symptoms.

Structural Neuroimaging of Hippocampus and Amygdala Subregions in Posttraumatic Stress Disorder: A Scoping Review.

Numerous studies have explored the relationship between posttraumatic stress disorder (PTSD) and the hippocampus and the amygdala because both regions are implicated in the disorder's pathogenesis and pathophysiology. Nevertheless, those key limbic regions consist of functionally and cytoarchitecturally distinct substructures that may play different roles in the etiology of PTSD. Spurred by the availability of automatic segmentation software, structural neuroimaging studies of human hippocampal and amygdala subregions have proliferated in recent years. Here, we present a preregistered scoping review of the existing structural neuroimaging studies of the hippocampus and amygdala subregions in adults diagnosed with PTSD. A total of 3513 studies assessing subregion volumes were identified, 1689 of which were screened, and 21 studies were eligible for this review (total N = 2876 individuals). Most studies examined hippocampal subregions and reported decreased CA1, CA3, dentate gyrus, and subiculum volumes in PTSD. Fewer studies investigated amygdala subregions and reported altered lateral, basal, and central nuclei volumes in PTSD. This review further highlights the conceptual and methodological limitations of the current literature and identifies future directions to increase understanding of the distinct roles of hippocampal and amygdalar subregions in posttraumatic psychopathology.

Effects of a dissociative drug on fronto-limbic resting-state functional connectivity in individuals with posttraumatic stress disorder: a randomized controlled pilot study.

RATIONALE: A subanesthetic dose of ketamine, a non-competitive N-methyl-D-aspartate glutamate receptor (NMDAR) antagonist, elicits dissociation in individuals with posttraumatic stress disorder (PTSD), who also often suffer from chronic dissociative symptoms in daily life. These debilitating symptoms have not only been linked to worse PTSD trajectories, but also to increased resting-state functional connectivity (RSFC) between medial prefrontal cortex (mPFC) and amygdala, supporting the conceptualization of dissociation as emotion overmodulation. Yet, as studies were observational, causal evidence is lacking. OBJECTIVES: The present randomized controlled pilot study examines the effect of ketamine, a dissociative drug, on RSFC between mPFC subregions and amygdala in individuals with PTSD. METHODS: Twenty-six individuals with PTSD received either ketamine (0.5mg/kg; n = 12) or the control drug midazolam (0.045mg/kg; n = 14) during functional magnetic resonance imaging (fMRI). RSFC between amygdala and mPFC subregions, i.e., ventromedial PFC (vmPFC), dorsomedial PFC (dmPFC) and anterior-medial PFC (amPFC), was assessed at baseline and during intravenous drug infusion. RESULTS: Contrary to pre-registered predictions, ketamine did not promote a greater increase in RSFC between amygdala and mPFC subregions from baseline to infusion compared to midazolam. Instead, ketamine elicited a stronger transient decrease in vmPFC-amygdala RSFC compared to midazolam. CONCLUSIONS: A dissociative drug did not increase fronto-limbic RSFC in individuals with PTSD. These preliminary experimental findings contrast with prior correlative findings and call for further exploration and, potentially, a more differentiated view on the neurobiological underpinning of dissociative phenomena in PTSD.

Underlying Hippocampal Mechanism of Posttraumatic Stress Disorder Treatment Outcome: Evidence From Two Clinical Trials.

Background: The hippocampus plays an important role in the pathophysiology of posttraumatic stress disorder (PTSD) and its prognosis. Accumulating findings suggest that individuals with larger pretreatment hippocampal volume are more likely to benefit from PTSD treatment, but the mechanism underlying this effect is unknown. We investigated whether further increase in hippocampal volume during treatment explains the better prognosis of individuals with greater pretreatment hippocampal volume. Methods: We collected structural magnetic resonance imagesfrom patients with PTSD before and after treatment. We examined whether larger hippocampal volume moderates the effect of increased hippocampal volume during treatment on symptom reduction. Given the relatively small sample sizes of treatment studies with pre- and posttreatment magnetic resonance imaging, we focused on effect sizes and sought to replicate findings in an external sample. We tested our hypothesis in study 1 (N = 38; prolonged exposure therapy) and then tested whether the results could be externally replicated in study 2 (N = 20; ketamine infusion followed by exposure therapy). Results: Findings from study 1 revealed that increased right hippocampal volume during treatment was associated with greater PTSD symptom reduction only in patients with greater pretreatment right hippocampal volume (p = .03; η2 = 0.13, a large effect). Findings were partially replicated in study 2 for depressive symptoms (p = .034; η2 = 0.25, a very large effect) and for PTSD symptoms (p = .15; η2 = 0.15, a large effect). Conclusions: Elucidating increased hippocampal volume as one of the neural mechanisms predictive of therapeutic outcome for individuals with larger pretreatment hippocampal volume may help identify clinical targets for this subgroup.

Correlates of avoidance coping in trauma-exposed U.S. military veterans: Results from the National Health and Resilience in Veterans Study.

Avoidant coping strategies, which involve cognitions and behaviors aimed to avoid dealing with stressful experiences, are associated with adverse long-term mental and physical health outcomes. In response to traumatic events, these strategies can be maladaptive as they may interfere with the adaptive integration of traumatic events into consolidated memories. Using data from a nationally representative sample of more than 3000 trauma-exposed U.S. military veterans (mean time since trauma 30.9 years, SD = 19.9), we employed a network analytic approach to examine pairwise associations between key sociodemographic, personality, and psychosocial risk factors in relation to the endorsement of avoidant coping strategies. Results revealed that negative affect symptoms of posttraumatic stress disorder (PTSD) and adverse childhood experiences were positively associated with engagement in avoidance coping, and that greater emotional stability and conscientiousness were negatively associated with this measure. Secondary network analysis of individual negative affect symptoms of PTSD suggested that blaming oneself and/or others for the traumatic event, emotional neglect, and sexual abuse were most strongly linked to avoidance coping. Collectively, these results suggest that strong feelings of blame related to trauma, emotional neglect, and sexual abuse are associated with greater likelihood of engaging in avoidance coping, while emotional stability and conscientiousness are associated with a lower likelihood of engaging in such strategies.

Long term structural and functional neural changes following a single infusion of Ketamine in PTSD.

NMDA receptor antagonists have a vital role in extinction, learning, and reconsolidation processes. During the reconsolidation window, memories are activated into a labile state and can be reconsolidated in an altered form. This concept might have significant clinical implications in treating PTSD. In this pilot study we tested the potential of a single infusion of ketamine, followed by brief exposure therapy, to enhance post-retrieval extinction of PTSD trauma memories. 27 individuals diagnosed with PTSD were randomly assigned to receive either ketamine (0.5 mg/kg 40 min; N = 14) or midazolam (0.045 mg/kg; N = 13) after retrieval of the traumatic memory. 24 h following infusion, participants received a four-day trauma-focused psychotherapy. Symptoms and brain activity were assessed before treatment, at the end of treatment, and at 30-day follow-up. Amygdala activation to trauma scripts (a major biomarker of fear response) served as the main study outcome. Although PTSD symptoms improved equally in both groups, post-treatment, ketamine recipients showed a lower amygdala (-0.33, sd = 0.13, 95%HDI [-0.56,-0.04]) and hippocampus (-0.3 (sd = 0.19), 95%HDI [-0.65, 0.04]; marginal effect) reactivation to trauma memories, compared to midazolam recipients. Post-retrieval ketamine administration was also associated with decreased connectivity between the amygdala and hippocampus (-0.28, sd = 0.11, 95%HDI [-0.46, -0.11]), with no change in amygdala-vmPFC connectivity. Moreover, reduction in fractional anisotropy in bi-lateral uncinate fasciculus was seen in the Ketamine recipients compared with the midazolam recipients (right: post-treatment: -0.01108, 95% HDI [-0.0184,-0.003]; follow-up: -0.0183, 95% HDI [-0.02719,-0.0107]; left: post-treatment: -0.019, 95% HDI [-0.028,-0.011]; follow-up: -0.017, 95% HDI [-0.026,-0.007]). Taken together it is possible that ketamine may enhance post-retrieval extinction of the original trauma memories in humans. These preliminary findings show promising direction toward the capacity to rewrite human traumatic memories and modulate the fear response for at least 30 days post-extinction. When combined with psychotherapy for PTSD, further investigation of ketamine dose, timing of administration, and frequency of administration, is warranted.

Longitudinal volumetric evaluation of hippocampus and amygdala subregions in recent trauma survivors.

The hippocampus and the amygdala play a central role in post-traumatic stress disorder (PTSD) pathogenesis. While alternations in volumes of both regions have been consistently observed in individuals with PTSD, it remains unknown whether these reflect pre-trauma vulnerability traits or acquired post-trauma consequences of the disorder. Here, we conducted a longitudinal panel study of adult civilian trauma survivors admitted to a general hospital emergency department (ED). One hundred eligible participants (mean age = 32.97 ± 10.97, n = 56 females) completed both clinical interviews and structural MRI scans at 1-, 6-, and 14-months after ED admission (alias T1, T2, and T3). While all participants met PTSD diagnosis at T1, only n = 29 still met PTSD diagnosis at T3 (a "non-Remission" Group), while n = 71 did not (a "Remission" Group). Bayesian multilevel modeling analysis showed robust evidence for smaller right hippocampus volume (P+ of ~0.014) and moderate evidence for larger left amygdala volume (P+ of ~0.870) at T1 in the "non-Remission" group, compared to the "Remission" group. Subregion analysis further demonstrated robust evidence for smaller volume in the subiculum and right CA1 hippocampal subregions (P+ of ~0.021-0.046) in the "non-Remission" group. No time-dependent volumetric changes (T1 to T2 to T3) were observed across all participants or between groups. Results support the "vulnerability trait" hypothesis, suggesting that lower initial volumes of specific hippocampus subregions are associated with non-remitting PTSD. The stable volume of all hippocampal and amygdala subregions does not support the idea of consequential, progressive, stress-related atrophy during the first critical year following trauma exposure.

Delirium screening in an acute care setting with a machine learning classifier based on routinely collected nursing data: A model development study.

Delirium screening in acute care settings is a resource intensive process with frequent deviations from screening protocols. A predictive model relying only on daily collected nursing data for delirium screening could expand the populations covered by such screening programs. Here, we present the results of the development and validation of a series of machine-learning based delirium prediction models. For this purpose, we used data of all patients 18 years or older which were hospitalized for more than a day between January 1, 2014, and December 31, 2018, at a single tertiary teaching hospital in Zurich, Switzerland. A total of 48,840 patients met inclusion criteria. 18,873 (38.6%) were excluded due to missing data. Mean age (SD) of the included 29,967 patients was 71.1 (12.2) years and 12,231 (40.8%) were women. Delirium was assessed with the Delirium Observation Scale (DOS) with a total score of 3 or greater indicating that a patient is at risk for delirium. Additional measures included structured data collected for nursing process planning and demographic characteristics. The performance of the machine learning models was assessed using the area under the receiver operating characteristic curve (AUC). The training set consisted of 21,147 patients (mean age 71.1 (12.1) years; 8,630 (40.8%) women|) including 233,024 observations with 16,167 (6.9%) positive DOS screens. The test set comprised 8,820 patients (median age 71.1 (12.4) years; 3,601 (40.8%) women) with 91,026 observations with 5,445 (6.0%) positive DOS screens. Overall, the gradient boosting machine model performed best with an AUC of 0.933 (95% CI, 0.929 - 0.936). In conclusion, machine learning models based only on structured nursing data can reliably predict patients at risk for delirium in an acute care setting. Prediction models, using existing data collection processes, could reduce the resources required for delirium screening procedures in clinical practice.

Emotional numbing in PTSD is associated with lower amygdala reactivity to pain.

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

The link between math anxiety and performance does not depend on working memory: A network analysis study.

Math anxiety (MA) and working memory (WM) influence math performance. Yet the interplay between them is not fully understood. Inconsistent results possibly stem from the multicomponent structure of math performance and WM. Using network analysis approach, we investigated the drivers of the MA, WM and math performance edges, and the contribution of each node to the network. First, 116 women completed a battery of tests and questionnaires. Second, we explored the generalizability of our model by applying it to a new data-set (Skagerlund et al., 2019; conceptual replication). The results revealed: (1) the links between MA and WM depend on specific task properties, specifically, WM tasks that require manipulation of numbers; (2) WM and MA are independently linked to math performance; and (3) each WM task is associated with different math abilities. The study provides a strong and reliable model showing the direct effects of math anxiety on math performance.

Math Anxiety Is Related to Math Difficulties and Composed of Emotion Regulation and Anxiety Predisposition: A Network Analysis Study.

Current evidence suggests emotion regulation is an important factor in both math anxiety and math performance, but the interplay between these constructs is unexamined. Given the multicomponent structure of math anxiety, emotion regulation, and math performance, here, we aimed to provide a comprehensive model of the underlying nature of the links between these latent variables. Using the innovative network analysis approach, the study visualized the underlying links between directly observable and measurable variables that might be masked by traditional statistical approaches. One hundred and seventeen adults completed a battery of tests and questionnaires on math anxiety, emotion regulation, and math performance. The results revealed: (1) state math anxiety (the emotional experience in math-related situations), rather than trait math anxiety, was linked to anxiety predisposition, subjective valence of math information, and difficulties in emotion regulation; (2) the link between state math anxiety and math performance partialed out the link between trait math anxiety and performance. The study innovatively demonstrates the need to differentiate between traits and tendencies to the actual emotional experience and emotion regulation used in math anxiety. The results have important implications for the theoretical understanding of math anxiety and future discussions and work in the field.

Cannabinoid Receptor 1 rs1049353 Variant, Childhood Abuse, and the Heterogeneity of PTSD Symptoms: Results From the National Health and Resilience in Veterans Study.

BACKGROUND: Accumulating evidence implicates the endocannabinoid system, including variants in the cannabinoid-1 receptor gene (CNR1), in the pathophysiology of posttraumatic stress disorder (PTSD). The synonymous G1359A variant (rs1049353) in the CNR1 gene has been linked to PTSD in individuals exposed to childhood abuse. In this study, the effects of the rs1049353 genotype and childhood abuse on overall PTSD symptoms, as well as PTSD symptom clusters were examined in order to examine how this interaction relates to the phenotypic expression of this disorder. METHOD: Data were analyzed from 1,372 Caucasian U.S. veterans who participated in the National Health and Resilience in Veterans Study. Multivariable analyses were conducted to evaluate the association between rs1049353 genotype, childhood abuse, and their interaction in relation to PTSD symptoms. RESULTS: A significant interaction between rs1049353 genotype and childhood abuse was observed, with A allele carriers with histories of childhood abuse reporting greater severity of PTSD symptoms, most notably anxious arousal, relative to G/G homozygotes. Significant main effects of childhood abuse on overall PTSD symptoms, and re-experiencing, emotional numbing, and dysphoric arousal symptom clusters, as well as of A allele carrier status on anxious arousal symptoms were observed. CONCLUSIONS: Results of this study replicate prior work and suggest that the rs1049353-by-childhood abuse interaction is particularly associated with the manifestation of anxious arousal symptoms of PTSD. Taken together, these findings underscore the importance of considering the phenotypic heterogeneity of PTSD in gene-environment studies of this multifaceted disorder.

Different neural activations for an approaching friend versus stranger: Linking personal space to numerical cognition.

INTRODUCTION: Typically, humans place themselves at a preferred distance from others. This distance is known to characterize human spatial behavior. Here, we focused on neurocognitive conditions that may affect interpersonal distances. The current study investigated whether neurocognitive deficiencies in numerical and spatial knowledge may affect social perception and modulate personal space. METHOD: In an event-related potential (ERP) study, university students with developmental dyscalculia (DD) and typically developing control participants were given a computerized version of the comfortable interpersonal distance task, in which participants were instructed to press the spacebar when they began to feel uncomfortable by the approach of a virtual protagonist. RESULTS: Results showed that students with deficiencies in numerical and spatial skills (i.e., DD) demonstrated reduced variability in their preferred distance from an approaching friend. Importantly, DD showed decreased amplitude of the N1 wave in the friend condition. CONCLUSION: These results suggest that people coping with deficiencies in spatial cognition have a less efficient allocation of spatial attention in the service of processing personal distances. Accordingly, the study highlights the fundamental role of spatial neurocognition in organizing social space.

Frequency-based Dissociation of Symbolic and Nonsymbolic Numerical Processing during Numerical Comparison.

Recent evidence suggests that during numerical calculation, symbolic and nonsymbolic processing are functionally distinct operations. Nevertheless, both roughly recruit the same brain areas (spatially overlapping networks in the parietal cortex) and happen at the same time (roughly 250 msec poststimulus onset). We tested the hypothesis that symbolic and nonsymbolic processing are segregated by means of functionally relevant networks in different frequency ranges: high gamma (above 50 Hz) for symbolic processing and lower beta (12-17 Hz) for nonsymbolic processing. EEG signals were quantified as participants compared either symbolic numbers or nonsymbolic quantities. Larger EEG gamma-band power was observed for more difficult symbolic comparisons (ratio of 0.8 between the two numbers) than for easier comparisons (ratio of 0.2) over frontocentral regions. Similarly, beta-band power was larger for more difficult nonsymbolic comparisons than for easier ones over parietal areas. These results confirm the existence of a functional dissociation in EEG oscillatory dynamics during numerical processing that is compatible with the notion of distinct linguistic processing of symbolic numbers and approximation of nonsymbolic numerical information.

Role of endocannabinoids in the hippocampus and amygdala in emotional memory and plasticity.

Posttraumatic stress disorder (PTSD) is characterized by the reexperiencing of a traumatic event and is associated with slower extinction of fear responses. Impaired extinction of fearful associations to trauma-related cues may interfere with treatment response, and extinction deficits may be premorbid risk factors for the development of PTSD. We examined the effects of exposure to a severe footshock followed by situational reminders (SRs) on extinction, plasticity, and endocannabinoid (eCB) content and activity in the hippocampal CA1 area and basolateral amygdala (BLA). We also examined whether enhancing eCB signaling before extinction, using the fatty acid amide hydrolase (FAAH) inhibitor URB597, could prevent the shock/SRs-induced effects on fear response and plasticity. URB597 administered systemically (0.3 mg/kg) or locally into the CA1 or BLA (0.1 µg/side) prior to extinction decreased fear retrieval and this effect persisted throughout extinction training and did not recuperate during spontaneous recovery. A low dose of the CB1 receptor antagonist AM251 (0.3 mg/kg i.p. or 0.01 µg/0.5 µl intra-CA1 or intra-BLA) blocked these effects suggesting that the effects of URB597 were CB1 receptor-dependent. Exposure to shock and reminders induced behavioral metaplasticity with opposite effects on long-term potentiation (LTP) in the hippocampus (impairment) and the BLA (enhancement). URB597 was found to prevent the opposite shock/SR-induced metaplasticity in hippocampal and BLA-LTP. Exposure to shock and reminders might cause variation in endogenous cannabinoid levels that could affect fear-circuit function. Indeed, exposure to shock and SRs affected eCB content: increased 2-arachidonoyl-glycerol (2-AG) and N-arachidonylethanolamine (AEA) levels in the CA1, decreased serum and BLA AEA levels while shock exposure increased FAAH activity in the CA1 and BLA. FAAH inhibition before extinction abolished fear and modulated LTP in the hippocampus and amygdala, brain regions pertinent to emotional memory. The findings suggest that targeting the eCB system before extinction may be beneficial in fear memory attenuation and these effects may involve metaplasticity in the CA1 and BLA.

Role of beta-catenin and endocannabinoids in the nucleus accumbens in extinction in rats exposed to shock and reminders.

The response to a traumatic experience may be rapid recovery or development of psychopathology such as post-traumatic stress disorder (PTSD). Impaired extinction of fear memories is thought to contribute to the development of the persistent trauma memories and avoidance. The Wnt/ß-catenin pathway and the endocannabinoid system appear to play significant roles in anxiety and depressive symptoms. Here we examined the involvement of ß-catenin in the nucleus accumbens (NAc) in extinction in rats exposed to the shock and reminders model of PTSD. We found that increased ß-catenin levels in the NAc were correlated with facilitated extinction kinetics in rats exposed to shock and reminders, suggesting that increased levels of NAc ß-catenin are associated with a resilient response to the stressor. Furthermore, downregulating ß-catenin expression in the NAc in shocked rats using sulindac (0.0178, 0.178mg/side) impaired extinction whereas upregulating the Wnt/ß-catenin pathway using LiCl (2µg/side) facilitated extinction. Exposure to shock and reminders resulted in attenuated levels of the endocannabinoid N-arachidonylethanolamine (AEA) in the NAc; the cannabinoid CB1/2 receptor agonist WIN55,212-2 (5µg/side) microinjected into the NAc facilitated extinction in shocked rats. Importantly, the facilitating effect of WIN55,212-2 on extinction was blocked by co-administration of sulindac in doses that downregulated ß-catenin levels. Taken together, the results suggest that ß-catenin in the NAc may serve as a protective buffer against the effects of severe stress, and that inhibiting this system in the NAc may prevent the therapeutic effects of cannabinoids against stress-related disorders.

Is susceptibility to cross-language interference domain specific?

The ability to overcome interference from the first-language (L1) is a source of variability in second language (L2) achievement, which has to date been explored mainly in same-script bilinguals. Such interference management, and bilingual language control more generally, have recently been linked to domain general executive functions (EF). In the current study, we examined L2 proficiency and executive functions as possible predictors of susceptibility to L1 interference during L2 processing, in bilinguals whose languages do not share an orthographic system. Seventy Arabic-Hebrew bilingual university students performed two tasks indexing cross-language interference (from L1 to L2). Lexical interference was assessed using a cross-modal semantic similarity judgment task in Hebrew, with false-cognates as critical items. Syntactic interference was assessed using a self-paced reading paradigm and grammaticality judgments on Hebrew sentences whose syntactic structures differed from those of Arabic. EFs were examined using spatial and numerical Stroop tasks, to index inhibitory control, and a task switching paradigm, to index shifting abilities. We found significant L1 interference across the lexical and syntactic domains, even in proficient different-script bilinguals. However, these interference effects were not correlated, and neither type of interference was related to domain general EF abilities. Finally, offline susceptibility to syntactic interference, but not lexical interference, was reduced with greater L2 proficiency. These results suggest at least partially independent mechanisms for managing interference in the two language domains, and raise questions regarding the degree to which domain general control abilities are recruited for managing L1 interference.

Cannabinoids reverse the effects of early stress on neurocognitive performance in adulthood.

Early life stress (ES) significantly increases predisposition to psychopathologies. Cannabinoids may cause cognitive deficits and exacerbate the effects of ES. Nevertheless, the endocannabinoid system has been suggested as a therapeutic target for the treatment of stress- and anxiety-related disorders. Here we examined whether cannabinoids administered during "late adolescence" (extensive cannabis use in humans at the ages 18-25) could reverse the long-term adverse effects of ES on neurocognitive function in adulthood. Male and female rats were exposed to ES during post-natal days (P) 7-14, injected with the cannabinoid CB1/2 receptor agonist WIN55,212-2 (WIN; 1.2 mg/kg, i.p.) for 2 wk during late adolescence (P45-60) and tested in adulthood (P90) for working memory, anxiety, and alterations in CB1 receptors (CB1r), and glucocorticoid receptors (GRs) in the stress circuit [hippocampus, prefrontal cortex (PFC), and basolateral amygdala (BLA)]. ES males and females exhibited impaired performance in short-term memory in adulthood in the spatial location and social recognition tasks; males were also impaired in the novel object recognition task. WIN administered during late adolescence prevented these stress-induced impairments and reduced anxiety levels. WIN normalized the ES-induced up-regulation in PFC-GRs and CA1-CB1r in females. In males, WIN normalized the ES-induced up-regulation in PFC-GR and down-regulation in BLA-CB1r. There is a crucial role of the endocannabinoid system in the effects of early life stress on behavior at adulthood. Differences in recognition memory and in the expression of GRs and CB1r in the fear circuit suggest sex differences in the mechanism underlying coping with stress.

The role of empathy in the neural responses to observed human social touch.

One of the ways in which individuals convey feelings and thoughts to one another is through touch. Although the neural responses to felt and observed tactile stimuli between an inanimate object and a part of the human body have been vastly explored, the neural responses to observed human interaction involving touch are not well understood. Considering that the observation of social touch involves vicarious sharing of emotions, we hypothesized that levels of empathic traits modulate the neural responses to observed touch and focused on the attenuation in the mu\alpha rhythm (8-13Hz), a neural marker that has been related to sensorimotor resonance. Fifty-four participants observed photos depicting social touch, nonsocial touch, or no touch while their electroencephalography (EEG) activity was recorded. Results showed that interindividual differences in levels of empathic traits modulated both behavioral and electrophysiological responses to human social touch, such that highly empathic participants evaluated human social touch as inducing more pleasant emotions and exhibited greater mu suppression upon observation of human social touch compared to less empathic participants. Specifically, both the behavioral and the electrophysiological responses to observed social touch were predicted by levels of personal distress, a measure of emotional contagion. These findings indicate that the behavioral and electrophysiological responses to observed social touch are modulated by levels of empathy.

Targeting the endocannabinoid system to treat anxiety-related disorders.

The endocannabinoid system plays an important role in the control of emotions, and its dysregulation has been implicated in several psychiatric disorders. The most common self-reported reason for using cannabis is rooted in its ability to reduce feelings of stress, tension, and anxiety. Nevertheless, there are only few studies in controlled clinical settings that confirm that administration of cannabinoids can benefit patients with a post-traumatic stress disorder (PTSD). There are considerable encouraging preclinical data to suggest that endocannabinoid-targeted therapeutics for anxiety disorders should continue. In this review, we will describe data supporting a role for the endocannabinoid system in preventing and treating anxiety-like behavior in animal models and PTSD patients. Cannabinoids have shown beneficial outcomes in rat and mouse models of anxiety and PTSD, but they also may have untoward effects that discourage their chronic usage, including anxiogenic effects. Hence, clinical and preclinical research on the endocannabinoid system should further study the effects of cannabinoids on anxiety and help determine whether the benefits of using exogenous cannabinoids outweigh the risks. In general, this review suggests that targeting the endocannabinoid system represents an attractive and novel approach to the treatment of anxiety-related disorders and, in particular, PTSD.