Self-construal modulates default mode network connectivity in refugees with PTSD.

BACKGROUND: While self-construal and posttraumatic stress disorder (PTSD) are independently associated with altered self-referential processes and underlying default mode network (DMN) functioning, no study has examined how self-construal affects DMN connectivity in PTSD. METHODS: A final sample of 93 refugee participants (48 with DSM-5 PTSD or sub-syndromal PTSD and 45 matched trauma-exposed controls) completed a 5-minute resting state fMRI scan to enable the observation of connectivity in the DMN and other core networks. A self-construal index was calculated by substracting scores on the collectivistic and individualistic sub-scales of the Self Construal Scale. RESULTS: Independent components analysis identified 9 active networks-of-interest, and functional network connectivity was determined. A significant interaction effect between PTSD and self-construal index was observed in the anterior ventromedial DMN, with spatial maps localizing this to the left ventromedial prefrontal cortex (vmPFC), extending to the ventral anterior cingulate cortex. This effect revealed that connectivity in the vMPFC showed greater reductions in those with PTSD with higher levels of collectivistic self-construal. LIMITATIONS: This is an observational study and causality cannot be assumed. The specialized sample of refugees means that the findings may not generalize to other trauma-exposed populations. CONCLUSIONS: Such a finding indicates that self-construal may shape the core neural architecture of PTSD, given that functional disruptions to the vmPFC underpin the core mechanisms of extinction learning, emotion dysregulation and self-referential processing in PTSD. Results have important implications for understanding the universality of neural disturbances in PTSD, and suggest that self-construal could be an important consideration in the assessment and treatment of post-traumatic stress reactions.

Reduced pre-attentive threat versus nonthreat signal discrimination in clinically healthy military personnel with recurrent combat exposure history: A preliminary event-related potential (ERP) study.

Evidence now suggests that traumatic-stress impacts brain functions even in the absence of acute-onset post-traumatic stress disorder (PTSD) symptoms. These neurophysiological changes have also been suggested to account for increased risks of PTSD symptoms later developing in the aftermath of subsequent trauma. However, surprisingly few studies have explicitly examined brain function dynamics in high-risk populations, such as combat exposed military personnel without diagnosable PTSD. To extend available research, facial expression sensitive N170 event-related potential (ERP) amplitudes were examined in a clinically healthy sample of active service military personnel with recurrent combat exposure history. Consistent with several established theories of delayed-onset PTSD vulnerability, higher N170 amplitudes to backward-masked fearful and neutral facial expressions correlated with higher levels of past combat exposure. Significantly elevated amplitudes to nonthreatening neutral facial expressions also resulted in an absence of normal threat-versus-nonthreat signal processing specificity. While a modest sample size and cross-sectional design are key limitations here, ongoing prospective-longitudinal follow-ups may shed further light on the precise aetiology and prognostic utility of these preliminary findings in the near future.

Alexithymia and treatment response for prolonged exposure therapy: An evaluation of outcomes and mechanisms.

Alexithymia is the inability to identify and recognize emotions. The present study examined the impact of alexithymia on prolonged exposure (PE) therapy. Participants (n = 68) with PTSD underwent 10 PE sessions. Alexithymia was assessed via the Toronto Alexithymia Scale (TAS-20) and the emotional clarity and awareness subscales of the Difficulties in Emotion Regulation Scale. Treatment outcomes were assessed via the PTSD checklist and Clinician-Administered PTSD Scale for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition at posttreatment and 6-month follow-up. Those with high alexithymia were more likely to endorse experiencing a full PTSD diagnosis immediately posttreatment, χ²(1) = 12.53, p = .002, and at 6-month follow-up, χ²(1) = 11.21, p = .004. Alexithymia was associated with delayed treatment effects on avoidance, with a significant reduction in symptomology observed from pre- to follow-up, t(51) = 4.52, p < .001, and not from pre- to posttreatment. Although both the low and high alexithymia groups showed significant changes in negative changes in thinking and mood, F(2, 14) = 9.18, p = .001, d = 1.57 and F(2, 50) = 13.86, p = .001, d = 1.49, respectively, the high alexithymia group exhibited a marginally lesser magnitude of treatment effect. Although those with significantly greater difficulties with emotional clarity were more likely to drop out of PE treatment, emotional clarity and awareness did not moderate treatment response. Our results confirm the efficacy of PE but also highlight that those with alexithymia show a delayed treatment response and may be at greater risk of pathology after treatment. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

A brain model of altered self-appraisal in social anxiety disorder.

The brain's default mode network has a central role in the processing of information concerning oneself. Dysfunction in this self-referential processing represents a key component of multiple mental health conditions, particularly social anxiety disorder (SAD). This case-control study aimed to clarify alterations to network dynamics present during self-appraisal in SAD participants. A total of 38 adolescents and young adults with SAD and 72 healthy control participants underwent a self-referential processing fMRI task. The task involved two primary conditions of interest: direct self-appraisal (thinking about oneself) and reflected self-appraisal (thinking about how others might think about oneself). Dynamic causal modeling and parametric empirical Bayes were then used to explore differences in the effective connectivity of the default mode network between groups. We observed connectivity differences between SAD and healthy control participants in the reflected self-appraisal but not the direct self-appraisal condition. Specifically, SAD participants exhibited greater excitatory connectivity from the posterior cingulate cortex (PCC) to medial prefrontal cortex (MPFC) and greater inhibitory connectivity from the inferior parietal lobule (IPL) to MPFC. In contrast, SAD participants exhibited reduced intrinsic connectivity in the absence of task modulation. This was illustrated by reduced excitatory connectivity from the PCC to MPFC and reduced inhibitory connectivity from the IPL to MPFC. As such, participants with SAD showed changes to afferent connections to the MPFC which occurred during both reflected self-appraisal as well as intrinsically. The presence of connectivity differences in reflected and not direct self-appraisal is consistent with the characteristic fear of negative social evaluation that is experienced by people with SAD.

Opponent intrinsic brain network connectivity profiles associated with posttraumatic fear and dysphoria symptoms in trauma-exposed refugees.

OBJECTIVE: Resting-state functional magnetic resonance imaging (rsfMRI) studies report functional alterations in the connectivity between intrinsic brain networks in posttraumatic stress disorder (PTSD), but PTSD heterogeneity is rarely considered. Evidence points to fear (e.g., reexperiencing) and dysphoria (e.g., withdrawal) symptom factors as important in PTSD presentations, including relating to variable emotion dysregulation patterns. This study, therefore, tested how fear and dysphoria posttraumatic symptoms were differentially associated with core network connectivity and emotion dysregulation behaviors in a large group of trauma-exposed refugees. METHOD: A final sample of 77 trauma-exposed participants completed a rsfMRI scan. Independent component analysis identified active networks and functional network connectivity (FNC) between networks was assessed. Fear and dysphoria posttraumatic symptoms were partially correlated with FNCs, and linear regression models examined relationships with self-reported difficulties in emotion regulation. RESULTS: Twenty-three active networks were identified, eight being in the networks of interest (p < .05 false discovery rate-corrected). Fear and dysphoria symptoms were specifically related to connectivity patterns between two subnetworks of the default mode network (DMN). Fear symptoms were negatively associated with anterior dorsomedial DMN (admDMN) and temporoparietal DMN (tpDMN) connectivity; whereas dysphoria symptoms were positively associated with admDMN-tpDMN connectivity. Additionally, admDMN-tpDMN connectivity was positively predicted by goal-directed emotion dysregulation but negatively predicted by poor emotional clarity. CONCLUSIONS: Fear and dysphoria posttraumatic symptoms showed opponent associations with admDMN and tpDMN connectivity, potentially reflecting patterns of under- and overemotion dysregulation associated with these symptom profiles respectively. Findings highlight the importance of considering posttraumatic heterogeneity when constructing neural models of PTSD. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Challenges and considerations for treating PTSD with medicinal cannabis: the Australian clinician's perspective.

INTRODUCTION: Preclinical and experimental research have provided promising evidence that medicinal cannabis may be efficacious in the treatment of posttraumatic stress disorder (PTSD). However, implementation of medicinal cannabis into routine clinical therapies may not be straightforward. AREAS COVERED: In this review, we describe some of the clinical, practical, and safety challenges that must be addressed for cannabis-based treatment of PTSD to be feasible in a real-world setting. These issues are especially prevalent if medicinal cannabis is to be combined with trauma-focused psychotherapy. EXPERT OPINION: Future consideration of the clinical and practical considerations of cannabis use in PTSD therapy will be essential to both the efficacy and safety of the treatment protocols that are being developed. These issues include dose timing and titration, potential for addiction, product formulation, windows of intervention, and route of administration. In particular, exposure therapy for PTSD involves recall of intense emotions, and the interaction between cannabis use and reliving of trauma memories must be explored in terms of patient safety and impact on therapeutic outcomes.

Posttraumatic Stress and Alexithymia: Symptom Associations.

ABSTRACT: There is a demonstrated association between alexithymia and posttraumatic stress disorder (PTSD). However, work has largely focused on male-dominant, high-risk occupation populations. We aimed to explore the relationship between posttraumatic stress (PTS) and alexithymia among 100 trauma-exposed female university students. Participants completed a Life Events Checklist, the PTSD Checklist for the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (PCL-5), and the Toronto Alexithymia Scale (TAS-20). Multiple regressions were run to examine whether alexithymia was associated with each of the PCL-5 subscales. The TAS-20 total scores were associated with total PTS scores, ß = 0.47, t(99) = 5.22, p < 0.001. On a subscale level, Difficulty in Identifying Feelings (DIF) was positively associated (ß = 0.50 to 0.41) with all PCL-5 subscales except for Avoidance. Our results align with research showing that for women, the DIF subscale is most strongly associated with PTS, in contrast with the literature on male samples, showing strongest associations with the Difficulties in Describing Feelings subscale, suggesting sex differences in associations between PTS and alexithymia. Our study supports the universality of the associations between alexithymia and PTS.

Frontoamygdalar Effective Connectivity in Youth Depression and Treatment Response.

BACKGROUND: Emotion regulation deficits are characteristic of youth depression and are underpinned by altered frontoamygdalar function. However, the causal dynamics of frontoamygdalar pathways in depression and how these dynamics relate to treatment prognosis remain unexplored. This study aimed to assess frontoamygdalar effective connectivity during cognitive reappraisal in youths with depression and to test whether pathway dynamics are predictive of individual response to combined cognitive behavioral therapy plus treatment with fluoxetine or placebo. METHODS: One hundred seven young people with moderate to severe depression and 94 healthy control participants completed a functional magnetic resonance imaging cognitive reappraisal task. After the task, 87 participants with depression were randomized and received 12 weeks of cognitive behavioral therapy plus either fluoxetine or placebo. Dynamic causal modeling was used to map frontoamygdalar effective connectivity during reappraisal and to assess the predictive capacity of baseline frontoamygdalar effective connectivity on depression diagnosis and posttreatment depression remission. RESULTS: Young people with depression showed weaker inhibitory modulation of ventrolateral prefrontal cortex to amygdala connectivity during reappraisal (0.29 Hz, posterior probability = 1.00). Leave-one-out cross-validation demonstrated that this effect was sufficiently large to predict individual diagnostic status (r = 0.20, p = .003). Posttreatment depression remission was associated with weaker excitatory ventromedial prefrontal cortex to amygdala connectivity (-0.56 Hz, posterior probability = 1.00) during reappraisal at baseline, though this effect did not predict individual remission status (r = -0.02, p = .561). CONCLUSIONS: Frontoamygdalar effective connectivity shows promise in identifying youth depression diagnosis, and circuits responsible for negative affect regulation are implicated in responsiveness to first-line depression treatments.

Refugee visa insecurity disrupts the brain's default mode network.

BACKGROUND: Research has largely focused on the psychological consequences of refugee trauma exposure, but refugees living with visa insecurity face an uncertain future that also adversely affects psychological functioning and self-determination. OBJECTIVE: This study aimed to examine how refugee visa insecurity affects the functional brain. METHOD: We measured resting state brain activity via fMRI in 47 refugees with insecure visas (i.e. temporary visa status) and 52 refugees with secure visas (i.e. permanent visa status) residing in Australia, matched on key demographic, trauma exposure and psychopathology. Data analysis comprised independent components analysis to identify active networks and dynamic functional causal modelling tested visa security group differences in network connectivity. RESULTS: We found that visa insecurity specifically affected sub-systems within the default mode network (DMN) - an intrinsic network subserving self-referential processes and mental simulations about the future. The insecure visa group showed less spectral power in the low frequency band in the anterior ventromedial DMN, and reduced activity in the posterior frontal DMN, compared to the secure visa group. Using functional dynamic causal modelling, we observed positive coupling between the anterior and posterior midline DMN hubs in the secure visa group, while the insecure visa group displayed negative coupling that correlated with self-reported fear of future deportation. CONCLUSIONS: Living with visa-related uncertainty appears to undermine synchrony between anterior-posterior midline components of the DMN responsible for governing the construction of the self and making mental representations of the future. This could represent a neural signature of refugee visa insecurity, which is marked by a perception of living in limbo and a truncated sense of the future.

Refugee visa insecurity disrupts default mode network (DMN) connectivity ­ a core network that supports the internal construction of the self.Refugees living with insecure visa status showed decreased connectivity in the DMN and more negative coupling between midline anterior­posterior hubs of the DMN, compared to refugees living with secure visas.Diminished DMN connectivity may represent a neural basis for the psychological effects of refugee visa insecurity, which is associated with prolonged uncertainty regarding the future self and increased risk for psychological distress.

Differential engagement of the posterior cingulate cortex during cognitive restructuring of negative self- and social beliefs.

Negative self-beliefs are a core feature of psychopathology, encompassing both negative appraisals about oneself directly (i.e. self-judgment) and negative inferences of how the self is appraised by others (i.e. social judgment). Challenging maladaptive self-beliefs via cognitive restructuring is a core treatment mechanism of gold-standard psychotherapies. However, the neural mechanisms underlying the restructuring of these two kinds of negative self-beliefs are poorly understood. Eighty-six healthy participants cognitively restructured self-judgment and social-judgment negative self-belief statements during 7 Tesla functional magnetic resonance imaging scanning. Cognitive restructuring broadly elicited activation in the core default mode network (DMN), salience and frontoparietal control regions. Restructuring self-judgment relative to social-judgment beliefs was associated with comparatively higher activation in the ventral posterior cingulate cortex (PCC)/retrosplenial cortex, while challenging social-judgment statements was associated with higher activation in the dorsal PCC/precuneus. While both regions showed increased functional connectivity with the supplementary and pre-supplementary motor areas during restructuring, the dorsal PCC displayed greater task-dependent connectivity with distributed regions involved in salience, attention and social cognition. Our findings indicate distinct patterns of PCC engagement contingent upon self- and social domains, highlighting a specialized role of the dorsal PCC in supporting neural interactions between the DMN and frontoparietal/salience networks during cognitive restructuring.

Sleep and day-to-day PTSD symptom variability: an ecological momentary assessment and actigraphy monitored study in trauma-exposed young adults.

BACKGROUND: Disrupted sleep and post-traumatic stress disorder (PTSD) are bi-directionally linked and have been found to mutually reinforce each other on a day-to-day basis. However, most of the previous research has focused on subjective measures of sleep only. OBJECTIVE: Here, we investigated the temporal relationship between sleep and PTSD symptoms using both subjective (sleep diary) and objective measures of sleep (actigraphy). METHODS: Forty-one non-treatment seeking, trauma exposed young adults (age M = 24.68, SD = 8.15) with a range of PTSD symptom severities (PTSS, 0-53 on PCL-5) were recruited. Participants completed two surveys per day over four weeks to measure day-time PTSD symptoms (i.e. PTSS and number of intrusions) and night-time sleep subjectively, while wearing an actigraphy watch to measure sleep objectively. RESULTS: Linear mixed models revealed that subjectively reported sleep disruptions were associated with elevated next-day PTSS and increasing number of intrusive memories both within and between participants. Similar results were found for daytime PTSD symptoms on night-time sleep. However, these associations were not found using objective sleep data. Exploratory moderator analyses including sex (male vs. female) found that these associations differed in strength between sexes but were generally in the same direction. DISCUSSION: These results were in line with our hypothesis with regards to the sleep diary (subjective sleep), but not actigraphy (objective sleep). Several factors which have implications on both PTSD and sleep, such as the COVID-19 pandemic and/ or sleep-state misperception, may be potential reasons behind those discrepancies. However, this study had limited power and needs to be replicated in larger samples. Nonetheless, these results add to the current literature about the bi-directional relationship between sleep and PTSD and have clinical implications for treatment strategies.

Elevated day-time PTSD symptom severity (PTSS) and more frequent intrusive memories were generally associated with subjectively reported disruptions in sleep and vice versa, but not with objective measures of sleep.While longer subjective sleep duration predicted reductions in PTSS and shorter sleep onset latency predicted reduced numbers of intrusions the next day, reduced daytime PTSS was only associated with reductions in distress associated with nightmares during the following night.Exploratory analyses showed that sex (men vs. women) moderated the bi-directional relationships between night-time sleep and day-time PTSD symptoms with longer sleep onset latency and lower sleep efficiency being related to worse PTSD symptoms the next day in women, but was not associated with men.

Changes in neural responses during affective and non-affective tasks and improvement of posttraumatic stress disorder symptoms following trauma-focused psychotherapy.

At least one-third posttraumatic stress disorder (PTSD) patients do not respond to trauma-focused psychotherapy (TF-psychotherapy), which is the treatment of choice for PTSD. To clarify the change mechanisms that may be associated with treatment response, this study examined changes in neural activations during affective and non-affective processing that occur with improvement of symptoms after TF-psychotherapy. This study assessed PTSD treatment-seeking patients (n = 27) prior to and after TF-psychotherapy using functional magnetic resonance imaging when they completed three tasks: (a) passive viewing of affective faces, (b) cognitive reappraisal of negative images, and (c) non-affective response inhibition. Patients then underwent 9 sessions of TF-psychotherapy, and were assessed on the Clinician-Administered PTSD Scale following treatment. Changes in neural responses in affect and cognitive processing regions-of-interest for each task were correlated with reduction of PTSD severity from pretreatment to posttreatment in the PTSD cohort. Data from 21 healthy controls was used for comparison. Improvement of symptoms in PTSD were associated with increased activation of left anterior insula, reductions in the left hippocampus and right posterior insula during viewing of supraliminally presented affective images, and reduced connectivity between the left hippocampus with the left amygdala and rostral anterior cingulate. Treatment response was also associated with reduced activation in the left dorsolateral prefrontal cortex during reappraisal of negative images. There were no associations between response and activation change during response inhibition. This pattern of findings indicates that improvement of PTSD symptoms following TF-psychotherapy is associated with changes in affective rather than non-affective processes. These findings accord with prevailing models that TF-psychotherapy promotes engagement and mastery of affective stimuli.Clinical Trials Registration: Trial Registration: Prospectively registered at Australian and New Zealand Clinical Trials Registry, ACTRN12612000185864 and ACTRN12609000324213. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=83857.

The influence of the BDNF Val66Met genotype on emotional recognition memory in post-traumatic stress disorder.

Dysregulated consolidation of emotional memories is a core feature of posttraumatic stress disorder (PTSD). Brain Derived Neurotrophic Factor (BDNF) influences synaptic plasticity and emotional memory consolidation. The BDNF Val66Met polymorphism has been associated with PTSD risk and memory deficits respectively, although findings have been inconsistent, potentially due to a failure to control for important confounds such as sex, ethnicity, and the timing/extent of previous trauma experiences. Furthermore, very little research has examined the impact of BDNF genotypes on emotional memory in PTSD populations. This study investigated the interaction effects of Val66Met and PTSD symptomatology in an emotional recognition memory task in 234 participants divided into healthy control (n = 85), trauma exposed (TE: n = 105) and PTSD (n = 44) groups. Key findings revealed impaired negative recognition memory in PTSD compared to control and TE groups and in participants with the Val/Met compared to the Val/Val genotype. There was a group × genotype interaction showing no Met effect in the TE group despite significant effects in PTSD and controls. Results suggest that people previously exposed to trauma who do not develop PTSD may be protected from the BDNF Met effect, however more research is needed to replicate findings and to explore the epigenetic and neural processes involved.

Subcortical contributions to salience network functioning during negative emotional processing.

Core regions of the salience network (SN), including the anterior insula (aINS) and dorsal anterior cingulate cortex (dACC), coordinate rapid adaptive changes in attentional and autonomic processes in response to negative emotional events. In doing so, the SN incorporates bottom-up signals from subcortical brain regions, such as the amygdala and periaqueductal gray (PAG). However, the precise influence of these subcortical regions is not well understood. Using ultra-high field 7-Tesla functional magnetic resonance imaging, this study investigated the bottom-up interactions of the amygdala and PAG with the SN during negative emotional salience processing. Thirty-seven healthy participants completed an emotional oddball paradigm designed to elicit a salient negative emotional response via the presentation of random, task-irrelevant negative emotional images. Negative emotional processing was associated with prominent activation in the SN, spanning the amygdala, PAG, aINS, and dACC. Consistent with previous research, analysis using dynamic causal modelling revealed an excitatory influence from the amygdala to the aINS, dACC, and PAG. In contrast, the PAG showed an inhibitory influence on amygdala, aINS and dACC activity. Our findings suggest that the amygdala may amplify the processing of negative emotional stimuli in the SN to enable upstream access to attentional resources. In comparison, the inhibitory influence of the PAG possibly reflects its involvement in modulating sympathetic-parasympathetic autonomic arousal mediated by the SN. This PAG-mediated effect may be driven by amygdala input and facilitate bottom-up processing of negative emotional stimuli. Overall, our results show that the amygdala and PAG modulate divergent functions of the SN during negative emotional processing.

Neural predictors of cognitive-behavior therapy outcome in anxiety-related disorders: a meta-analysis of task-based fMRI studies.

BACKGROUND: Cognitive-behavior therapy (CBT) is a well-established first-line intervention for anxiety-related disorders, including specific phobia, social anxiety disorder, panic disorder/agoraphobia, generalized anxiety disorder, obsessive-compulsive disorder, and posttraumatic stress disorder. Several neural predictors of CBT outcome for anxiety-related disorders have been proposed, but previous results are inconsistent. METHODS: We conducted a systematic review and meta-analysis of task-based functional magnetic resonance imaging (fMRI) studies investigating whole-brain predictors of CBT outcome in anxiety-related disorders (17 studies, n = 442). RESULTS: Across different tasks, we observed that brain response in a network of regions involved in salience and interoception processing, encompassing fronto-insular (the right inferior frontal gyrus-anterior insular cortex) and fronto-limbic (the dorsomedial prefrontal cortex-dorsal anterior cingulate cortex) cortices was strongly associated with a positive CBT outcome. CONCLUSIONS: Our results suggest that there are robust neural predictors of CBT outcome in anxiety-related disorders that may eventually lead (probably in combination with other data) to develop personalized approaches for the treatment of these mental disorders.

Emotion response disconcordance among trauma-exposed adults: the impact of alexithymia.

BACKGROUND: Emotion processing deficits have been identified as a critical transdiagnostic factor that facilitates distress after trauma exposure. Limited skills in identifying and labelling emotional states (i.e. alexithymia) may present on the more automated (less conscious) end of the spectrum of emotional awareness and clarity. Individuals with alexithymia tend to exhibit a disconcordance between subjective experience and autonomic activity (e.g. where high levels of subjective emotional intensity are associated with low physiological arousal), which may exacerbate distress. Although there is a robust link between alexithymia and trauma exposure, no work to date has explored whether alexithymia is associated with emotional response disconcordance among trauma-exposed adults. METHOD: Using a validated trauma script paradigm, the present study explored the impact of alexithymia on emotion response concordance [skin conductance (Galvanic Skin Response, GSR) and Total Mood Disturbance (TMD)] among 74 trauma-exposed adults recruited via a posttraumatic stress disorder (PTSD) treatment clinic and student research programme. RESULTS: Unlike posttraumatic symptom severity, age, sex, participant type and mood (which showed no effect on emotion response concordance), alexithymia was associated with heightened emotion response disconcordance between GSR and TMD [F(1, 37) = 8.93, p = 0.006], with low GSR being associated with high TMD. Observed effects of the trauma script were entirely accounted for by the interaction with alexithymia, such that those with alexithymia showed a negligible association between subjective and physiological states. CONCLUSION: This finding is paramount as it shows that a large proportion of trauma-exposed adults have a divergent emotion engagement profile.

Sex differences in the effect of subjective sleep on fear conditioning, extinction learning, and extinction recall in individuals with a range of PTSD symptom severity.

Sleep has been found to play a key role in fear conditioning, extinction learning and extinction recall, and sleep disturbances are linked to many mental disorders including post-traumatic stress disorder (PTSD). Previous studies examining associations between sleep and fear or extinction processes primarily focused on objectively measured sleep architecture. Little research has so far focused on subjective sleep measures and particularly in clinical populations, which often experience subjectively poor sleep, including PTSD. Here we investigated whether subjective sleep disturbance, sleep onset latency, wake after sleep onset or sleep efficiency were related to fear conditioning, extinction learning or extinction recall in a large sample of individuals with a range of PTSD symptom severity (n = 248). Overall, we did not find that subjective sleep was associated with fear conditioning or extinction processes. However, exploratory analyses examining the moderating effect of sex found that shorter sleep onset latency and greater sleep efficiency were associated with improved extinction recall in women with higher PTSD symptom severity. This suggests that less time falling asleep and longer time asleep while in bed may be protective in highly symptomatic women against the commonly observed impaired extinction recall in PTSD. More studies are needed to explore sex-specific effects further.

The neurobiology of Pavlovian safety learning: Towards an acquisition-expression framework.

Safety learning creates associations between conditional stimuli and the absence of threat. Studies of human fear conditioning have accumulated evidence for the neural signatures of safety over various paradigms, aligning on several common brain systems. While these systems are often interpreted as underlying safety learning in a generic sense, they may instead reflect the expression of learned safety, pertaining to processes of fear inhibition, positive affect, and memory. Animal models strongly suggest these can be separable from neural circuits implicated in the conditioning process itself (or safety acquisition). While acquisition-expression distinctions are ubiquitous in behavioural science, this lens has not been applied to safety learning, which remains a novel area in the field. In this mini-review, we overview findings from prevalent safety paradigms in humans, and synthesise these with insights from animal models to propose that the neurobiology of safety learning be conceptualised along an acquisition-expression model, with the aim of stimulating richer brain-based characterisations of this important process.

Cortico-Striatal Activity Characterizes Human Safety Learning via Pavlovian Conditioned Inhibition.

Safety learning generates associative links between neutral stimuli and the absence of threat, promoting the inhibition of fear and security-seeking behaviors. Precisely how safety learning is mediated at the level of underlying brain systems, particularly in humans, remains unclear. Here, we integrated a novel Pavlovian conditioned inhibition task with ultra-high field (7 Tesla) fMRI to examine the neural basis of safety learning in 49 healthy participants. In our task, participants were conditioned to two safety signals: a conditioned inhibitor that predicted threat omission when paired with a known threat signal (A+/AX-), and a standard safety signal that generally predicted threat omission (BC-). Both safety signals evoked equivalent autonomic and subjective learning responses but diverged strongly in terms of underlying brain activation (PFDR whole-brain corrected). The conditioned inhibitor was characterized by more prominent activation of the dorsal striatum, anterior insular, and dorsolateral PFC compared with the standard safety signal, whereas the latter evoked greater activation of the ventromedial PFC, posterior cingulate, and hippocampus, among other regions. Further analyses of the conditioned inhibitor indicated that its initial learning was characterized by consistent engagement of dorsal striatal, midbrain, thalamic, premotor, and prefrontal subregions. These findings suggest that safety learning via conditioned inhibition involves a distributed cortico-striatal circuitry, separable from broader cortical regions involved with processing standard safety signals (e.g., CS-). This cortico-striatal system could represent a novel neural substrate of safety learning, underlying the initial generation of "stimulus-safety" associations, distinct from wider cortical correlates of safety processing, which facilitate the behavioral outcomes of learning.SIGNIFICANCE STATEMENT Identifying safety is critical for maintaining adaptive levels of anxiety, but the neural mechanisms of human safety learning remain unclear. Using 7 Tesla fMRI, we compared learning-related brain activity for a conditioned inhibitor, which actively predicted threat omission, and a standard safety signal (CS-), which was passively unpaired with threat. The inhibitor engaged an extended circuitry primarily featuring the dorsal striatum, along with thalamic, midbrain, and premotor/PFC regions. The CS- exclusively involved cortical safety-related regions observed in basic safety conditioning, such as the vmPFC. These findings extend current models to include learning-specific mechanisms for encoding stimulus-safety associations, which might be distinguished from expression-related cortical mechanisms. These insights may suggest novel avenues for targeting dysfunctional safety learning in psychopathology.

Methodological implications of sample size and extinction gradient on the robustness of fear conditioning across different analytic strategies.

Fear conditioning paradigms are critical to understanding anxiety-related disorders, but studies use an inconsistent array of methods to quantify the same underlying learning process. We previously demonstrated that selection of trials from different stages of experimental phases and inconsistent use of average compared to trial-by-trial analysis can deliver significantly divergent outcomes, regardless of whether the data is analysed with extinction as a single effect, as a learning process over the course of the experiment, or in relation to acquisition learning. Since small sample sizes are attributed as sources of poor replicability in psychological science, in this study we aimed to investigate if changes in sample size influences the divergences that occur when different kinds of fear conditioning analyses are used. We analysed a large data set of fear acquisition and extinction learning (N = 379), measured via skin conductance responses (SCRs), which was resampled with replacement to create a wide range of bootstrapped databases (N = 30, N = 60, N = 120, N = 180, N = 240, N = 360, N = 480, N = 600, N = 720, N = 840, N = 960, N = 1080, N = 1200, N = 1500, N = 1750, N = 2000) and tested whether use of different analyses continued to produce deviating outcomes. We found that sample size did not significantly influence the effects of inconsistent analytic strategy when no group-level effect was included but found strategy-dependent effects when group-level effects were simulated. These findings suggest that confounds incurred by inconsistent analyses remain stable in the face of sample size variation, but only under specific circumstances with overall robustness strongly hinging on the relationship between experimental design and choice of analyses. This supports the view that such variations reflect a more fundamental confound in psychological science-the measurement of a single process by multiple methods.