Prospective Bidirectional Relationship Between Sleep Duration and Posttraumatic Stress Disorder Symptoms After Suspected Acute Coronary Syndrome.

OBJECTIVE: Sleep disturbance is a "hallmark" symptom of posttraumatic stress disorder (PTSD). Poor sleep (including short sleep) after combat-related trauma can also predict subsequent PTSD. Less is known about the association between sleep duration and PTSD symptoms when PTSD is induced by acute coronary syndrome (ACS). We examined the bidirectional relationship between sleep duration and PTSD symptoms over the year after hospital evaluation for ACS. METHODS: Participants were enrolled in this observational study after emergency department evaluation for ACS. Sleep duration ("During the past month, how many hours of actual sleep did you get at night?") and cardiac event or hospitalization-induced PTSD symptoms (PTSD Checklist) were assessed at 1, 6, and 12 months after hospital discharge. Cross-lagged path analysis was used to model the effects of sleep duration and PTSD symptoms on each other. Covariates included age, sex, race/ethnicity, cardiac severity, baseline depression symptoms, and early acute stress disorder symptoms. RESULTS: The sample included 1145 participants; 16% screened positive for probable PTSD (PTSD Checklist score ≥33). Mean sleep duration across time points was 6.1 hours. Higher PTSD symptoms predicted shorter sleep duration at the next time point (i.e., 1-6 and 6-12 months; B = -0.14 hours/10-point difference, SE = 0.03, p < .001). Shorter sleep duration was associated with higher PTSD symptoms at the next time point (B = -0.25 points/hour, SE = 0.12, p = .04). CONCLUSIONS: Short sleep duration and PTSD symptoms are mutually reinforcing across the first year after ACS evaluation. Findings suggest that sleep, PTSD symptoms, and their relationship should be considered in the post-ACS period.

The central executive network moderates the relationship between posttraumatic stress symptom severity and gastrointestinal related issues.

Although most adults experience at least one traumatic event in their lifetime, a smaller proportion will go on to be clinically diagnosed with post-traumatic stress disorder (PTSD). Persons diagnosed with PTSD have a greater likelihood of developing gastrointestinal (GI) disorders. However, the extent to which subclinical levels of post-traumatic stress (PTS) correspond with the incidence of GI issues in a normative sample is unclear. Resting state fMRI, medical history, psychological survey, and anthropometric data were acquired from the Enhanced Nathan Kline Institute-Rockland Sample (n = 378; age range 18-85.6 years). The primary aim of this study was to test the main effect of subclinical PTS symptom severity on the number of endorsed GI issues. The secondary aim was to test the moderating effect of high versus low resting state functional connectivity (rsFC) of the central executive network (CEN) on the relationship between PTS symptom severity and GI issues. Trauma Symptom Checklist-40 (TSC-40) scores were positively associated with the number of endorsed GI issues (b = -0.038, SE = .009, p < .001). The interaction between TSC-40 scores and rsFC within the CEN was significant on GI issues after controlling for sociodemographic and cardiometabolic variables (b = -0.031, SE = .016, p < .05), such that above average rsFC within the CEN buffered the effect of TSC-40 scores on GI issues. Our findings of higher rsFC within the CEN moderating the magnitude of coincidence in PTS and GI symptom severity may reflect the mitigating role of executive control processes in the putative stress signaling mechanisms that contribute to gut dysbiosis.

Spaced conditioned stimulus presentation facilitates the extinction of strong fear memory in mice.

Inducing fear memory extinction by re-presenting a conditioned stimulus (CS) is the foundation of exposure therapy for post-traumatic stress disorder (PTSD). Investigating differences in the ability of different CS presentation patterns to induce extinction learning is crucial for improving this type of therapy. Using a trace fear conditioning paradigm in mice, we demonstrate that spaced presentation of the CS facilitated the extinction of a strong fear memory to a greater extent than continuous CS presentation. These results lay the groundwork for developing more effective exposure therapy techniques for PTSD.

Cortico-limbic interactions and carotid atherosclerotic burden during chronic stress exposure.

BACKGROUND AND AIMS: Chronic stress associates with cardiovascular disease, but mechanisms remain incompletely defined. Advanced imaging was used to identify stress-related neural imaging phenotypes associated with atherosclerosis. METHODS: Twenty-seven individuals with post-traumatic stress disorder (PTSD), 45 trauma-exposed controls without PTSD, and 22 healthy controls underwent 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI). Atherosclerotic inflammation and burden were assessed using 18F-FDG PET (as maximal target-to-background ratio, TBR max) and MRI, respectively. Inflammation was assessed using high-sensitivity C-reactive protein (hsCRP) and leucopoietic imaging (18F-FDG PET uptake in spleen and bone marrow). Stress-associated neural network activity (SNA) was assessed on 18F-FDG PET as amygdala relative to ventromedial prefrontal cortex (vmPFC) activity. MRI diffusion tensor imaging assessed the axonal integrity (AI) of the uncinate fasciculus (major white matter tract connecting vmPFC and amygdala). RESULTS: Median age was 37 years old and 54% of participants were female. There were no significant differences in atherosclerotic inflammation between participants with PTSD and controls; adjusted mean difference in TBR max (95% confidence interval) of the aorta 0.020 (-0.098, 0.138), and of the carotids 0.014 (-0.091, 0.119). Participants with PTSD had higher hsCRP, spleen activity, and aorta atherosclerotic burden (normalized wall index). Participants with PTSD also had higher SNA and lower AI. Across the cohort, carotid atherosclerotic burden (standard deviation of wall thickness) associated positively with SNA and negatively with AI independent of Framingham risk score. CONCLUSIONS: In this study of limited size, participants with PTSD did not have higher atherosclerotic inflammation than controls. Notably, impaired cortico-limbic interactions (higher amygdala relative to vmPFC activity or disruption of their intercommunication) associated with carotid atherosclerotic burden. Larger studies are needed to refine these findings.

Eye movement intervention facilitates concurrent perception and memory processing.

A widely used psychotherapeutic treatment for post-traumatic stress disorder (PTSD) involves performing bilateral eye movement (EM) during trauma memory retrieval. However, how this treatment-described as eye movement desensitization and reprocessing (EMDR)-alleviates trauma-related symptoms is unclear. While conventional theories suggest that bilateral EM interferes with concurrently retrieved trauma memories by taxing the limited working memory resources, here, we propose that bilateral EM actually facilitates information processing. In two EEG experiments, we replicated the bilateral EM procedure of EMDR, having participants engaging in continuous bilateral EM or receiving bilateral sensory stimulation (BS) as a control while retrieving short- or long-term memory. During EM or BS, we presented bystander images or memory cues to probe neural representations of perceptual and memory information. Multivariate pattern analysis of the EEG signals revealed that bilateral EM enhanced neural representations of simultaneously processed perceptual and memory information. This enhancement was accompanied by heightened visual responses and increased neural excitability in the occipital region. Furthermore, bilateral EM increased information transmission from the occipital to the frontoparietal region, indicating facilitated information transition from low-level perceptual representation to high-level memory representation. These findings argue for theories that emphasize information facilitation rather than disruption in the EMDR treatment.

A prospective study on EEG default mode network associated with subsequent posttraumatic stress disorder following sexual assault.

This study aimed to explore the predictors of posttraumatic stress disorder (PTSD) in women who have recently experienced sexual assault, by examining psychological and neurophysiological factors using a prospective design with resting-state electroencephalogram (EEG) functional connectivity. The study enrolled 33 women who had been recently traumatized by sexual assault and conducted assessments within a month of the trauma. These survivors were evaluated for PTSD three months later and were classified into two groups: PTSD positive (n = 12) and PTSD negative (n = 21). They were compared to two control groups comprising women who had not experienced any extremely traumatic events: 25 with depression and 25 healthy controls. The evaluation focused on resting-state EEG functional connectivity within default mode network (DMN) using small-worldness (SW), based on graph theory. We also assessed self-reported levels of depression, anxiety, anger, and executive functions. The findings indicated that survivors who developed PTSD three months post-trauma exhibited higher anxiety levels and reduced DMN SW in the beta 3 frequency, compared to those who did not develop PTSD. Contrary to expectations, survivors without PTSD showed decreased executive functioning and lower prefrontal centrality compared to those with PTSD. This study underscores the importance of early assessment and intervention for sexual assault survivors at risk of developing PTSD.

Contemporaneous and temporal network analysis of complex Posttraumatic stress disorder among Chinese college students with Childhood adversity: A longitudinal study.

OBJECTIVE: To enhance understanding of the longitudinal progression of complex posttraumatic stress disorder (CPTSD) symptoms, this longitudinal study examined how CPTSD symptoms interact over time in Chinese college students with childhood trauma. METHODS: From 18,933 college students who took part in two surveys 12 months apart, 4,006 participants who reported adverse childhood experiences were screened. Cross-sectional network comparisons and cross-lagged panel network (CLPN) analysis characterized interactions among CPTSD symptoms. RESULTS: In the cross-sectional networks, feeling like a failure and avoid activities reminiscent of the trauma were the central symptoms. Takes long time to calm down and exaggerated startle are important bridge symptoms in the two networks respectively. The comparison of cross-sectional networks indicates that the global network strength was stable. The findings of the CLPN model reveal that feel worthless and feel like a failure had the highest "out" expected influence; exaggerated startle and avoid thoughts and feelings about the trauma had the highest "in" expected influence. CONCLUSIONS: By conducting cross-sectional network analyses, the study illuminated the attributes of CPTSD networks across various time points. Additionally, the CLPN analysis uncovered the longitudinal patterns of CPTSD symptoms.

Hippocampus, amygdala, and insula activation in response to romantic relationship dissolution stimuli: A case-case-control fMRI study on emerging adult students.

BACKGROUND: Romantic relationship dissolutions (RRDs) are associated with posttraumatic stress symptoms (PTSS). Functional magnetic resonance imaging in RRD studies indicate overlapping neural activation similar to posttraumatic stress disorder. These studies combine real and hypothetical rejection, and lack contextual information and control and/or comparison groups exposed to non-RRD or DSM-5 defined traumatic events. AIM: We investigated blood oxygen level dependent (BOLD) activation in the hippocampus, amygdala, and insula of participants with RRDs compared with other traumatic or non-trauma stressors. METHODS: Emerging adults (mean age = 21.54 years; female = 74.7 %) who experienced an RRD (n = 36), DSM-5 defined trauma (physical and/or sexual assault: n = 15), or a non-RRD or DSM-5 stressor (n = 28) completed PTSS, depression, childhood trauma, lifetime trauma exposure, and attachment measures. We used a general and customised version of the International Affective Picture System to investigate responses to index-trauma-related stimuli. We used mixed linear models to assess between-group differences, and ANOVAs and Spearman's correlations to analyse factors associated with BOLD activation. RESULTS: BOLD activity increased between index-trauma stimuli as compared to neutral stimuli in the hippocampus and amygdala, with no significant difference between the DSM-5 Trauma and RRD groups. Childhood adversity, sexual orientation, and attachment style were associated with BOLD activation changes. Breakup characteristics (e.g., initiator status) were associated with increased BOLD activation in the hippocampus and amygdala, in the RRD group. CONCLUSION: RRDs should be considered as potentially traumatic events. Breakup characteristics are risk factors for experiencing RRDs as traumatic. LIMITATION: Future studies should consider more diverse representation across sex, ethnicity, and sexual orientation.

Effects of mindfulness-based interventions on symptoms and interoception in trauma-related disorders and exposure to traumatic events: Systematic review and meta-analysis.

Interoception is defined as the sense of the internal state of the body. Dysfunctions in interoception are found in several mental disorders, including trauma-related conditions. Mindfulness-Based Interventions (MBIs) have been shown to influence interoceptive processes. Randomised controlled trials (RCTs) have investigated whether MBIs impact symptoms and interoception in patients with trauma-related disorders. We undertook a systematic review and meta-analysis to synthesize these data. We included RCTs with an MBI arm which enrolled adult patients with trauma related-disorders or exposure to a traumatic experience, and addressed changes in interoception and trauma-related symptoms. A random-effects multivariate meta-analytic model was performed to quantify group differences in score change from baseline to follow-up. Twelve studies were included in the systematic review, and eleven in the meta-analysis. Overall, MBIs showed small to moderate positive effects on both interoception and symptoms. Despite a high heterogeneity in results, sensitivity analyses confirmed the robustness of the findings. We conclude that the efficacy of MBIs on trauma-related symptoms and interoception is supported by randomised evidence. However, further research is needed to understand whether changes in interoception might underpin the effectiveness of MBIs in trauma-related disorders.

Brain morphological changes and functional neuroanatomy related to cognitive and emotional distractors during working memory maintenance in post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is associated with abnormalities in the processing and regulation of emotion as well as cognitive deficits. This study evaluated the differential brain activation patterns associated with cognitive and emotional distractors during working memory (WM) maintenance for human faces between patients with PTSD and healthy controls (HCs) and assessed the relationship between changes in the activation patterns by the opposing effects of distraction types and gray matter volume (GMV). Twenty-two patients with PTSD and twenty-two HCs underwent T1-weighted magnetic resonance imaging (MRI) and event-related functional MRI (fMRI), respectively. Event-related fMRI data were recorded while subjects performed a delayed-response WM task with human face and trauma-related distractors. Compared to the HCs, the patients with PTSD showed significantly reduced GMV of the inferior frontal gyrus (IFG) (p < 0.05, FWE-corrected). For the human face distractor trial, the patients showed significantly decreased activities in the superior frontal gyrus and IFG compared with HCs (p < 0.05, FWE-corrected). The patients showed lower accuracy scores and slower reaction times for the face recognition task with trauma-related distractors compared with HCs as well as significantly increased brain activity in the STG during the trauma-related distractor trial was observed (p < 0.05, FWE-corrected). Such differential brain activation patterns associated with the effects of distraction in PTSD patients may be linked to neural mechanisms associated with impairments in both cognitive control for confusable distractors and the ability to control emotional distraction.

The memory trace of an intrusive trauma-analog episode.

Intrusive memories are a core symptom of posttraumatic stress disorder. Compared with memories of everyday events, they are characterized by several seemingly contradictory features: intrusive memories contain distinct sensory and emotional details of the traumatic event and can be triggered by various perceptually similar cues, but they are poorly integrated into conceptual memory. Here, we conduct exploratory whole-brain analyses to investigate the neural representations of trauma-analog experiences and how they are reactivated during memory intrusions. We show that trauma-analog movies induce excessive processing and generalized representations in sensory areas but decreased blood-oxygen-level-dependent (BOLD) responses and highly distinct representations in conceptual/semantic areas. Intrusive memories activate generalized representations in sensory areas and reactivate memory traces specific to trauma-analog events in the anterior cingulate cortex. These findings provide the first evidence of how traumatic events could distort memory representations in the human brain, which may form the basis for future confirmatory research on the neural representations of traumatic experiences.

Non-fear emotions in changes in posttraumatic stress disorder symptoms during treatment.

BACKGROUND AND OBJECTIVES: Posttraumatic stress disorder (PTSD) is not only associated with fear but also with other emotions. The present study aimed to examine if changes in shame, guilt, anger, and disgust predicted changes in PTSD symptoms during treatment, while also testing if PTSD symptoms, in turn, predicted changes in these emotions. METHODS: Participants (N = 155) with childhood-related PTSD received a maximum of 12 sessions of eye movement desensitization and reprocessing or imagery rescripting. The data was analyzed using Granger causality models across 12 treatment sessions and 6 assessment sessions (up until one year after the start of treatment). Differences between the two treatments were explored. RESULTS: Across treatment sessions, shame, and disgust showed a reciprocal relationship with PTSD symptoms, while changes in guilt preceded PTSD symptoms. Across assessments, anger was reciprocally related to PTSD, suggesting that anger might play a more important role in the longer term. LIMITATIONS: The individual emotion items were not yet validated, and the CAPS was not administered at all assessments. CONCLUSIONS: These findings partly differ from earlier studies that suggested a unidirectional relationship in which changes in emotions preceded changes in PTSD symptoms during treatment. This is in line with the idea that non-fear emotions do play an important role in the treatment of PTSD and constitute an important focus of treatment and further research.

Maladaptation of dentate gyrus mossy cells mediates contextual discrimination deficit after traumatic stress.

Fear overgeneralization is a maladaptive response to traumatic stress that is associated with the inability to discriminate between threat and safety contexts, a hallmark feature of post-traumatic stress disorder (PTSD). However, the neural mechanisms underlying this deficit remain unclear. Here, we show that traumatic stress exposure impairs contextual discrimination between threat and safety contexts in the learned helplessness (LH) model. Mossy cells (MCs) in the dorsal hippocampus are suppressed in response to traumatic stress. Bidirectional manipulation of MC activity in the LH model reveals that MC inhibition is causally linked to impaired contextual discrimination. Mechanistically, MC inhibition increases the number of active granule cells in a given context, significantly overlapping context-specific ensembles. Our study demonstrates that maladaptive inhibition of MCs after traumatic stress is a substantial mechanism underlying fear overgeneralization with contextual discrimination deficit, suggesting a potential therapeutic target for cognitive symptoms of PTSD.

Dyadic Investigation of Posttraumatic Stress Symptoms and Daily Sleep Health in Patients With Cancer and Their Caregivers.

OBJECTIVE: Cancer can be a traumatic experience affecting multidimensional aspects of sleep among patients and caregivers. This study examined the differential associations of cancer-related posttraumatic stress symptoms (PTSS) with various sleep markers in this population. METHODS: Patients newly diagnosed with colorectal cancer ( n = 138, mean age = 56.93 years, 31.88% female, 60.14% Hispanic, 6.53 months after diagnosis) and their sleep-partner caregivers ( n = 138, mean age = 55.32 years, 68.12% female, 57.97% Hispanic) completed questionnaires assessing the four PTSS clusters (intrusion, avoidance, alterations in arousal and reactivity, negative alterations in cognitions and mood). Participants also completed daily sleep diaries for 14 consecutive days, from which sleep onset latency (SOL), wake after sleep onset (WASO), and sleep duration were derived. RESULTS: Actor-partner interdependence model revealed that caregivers' greater alterations in arousal and reactivity were associated with their own longer SOL ( b = 15.59, p < .001) and their patients' longer sleep duration ( b = 0.61, p = .014), whereas patients' arousal and reactivity were associated with their caregivers' shorter SOL ( b = -8.47, p = .050). Patients' and caregivers' greater negative alterations in cognitions and mood were associated with patients' longer SOL ( b = 9.15, p = .014) and shorter sleep duration ( b = -0.41, p = .050), respectively. Caregivers' greater intrusion was related to their own shorter SOL ( b = -10.14, p = .004). CONCLUSIONS: The four PTSS clusters, particularly arousal and reactivity and negative cognitions and mood, have distinct associations with sleep markers individually and dyadically in patients and caregivers affected by cancer. Investigations of psychosocial and biobehavioral pathways underlying these relations are warranted. Tailored trauma treatments and sleep interventions may improve the well-being of this population.

Psilocybe cubensis extract potently prevents fear memory recall and freezing behavior in short- but not long-term in a rat model of posttraumatic stress disorder.

Psilocybe cubensis is a species of psilocybin mushroom (magic mushroom) of moderate potency whose principal active compounds are psilocybin and psilocin. Recent studies have shown the significant procognitive and mood-enhancer effects of Psilocybe cubensis. However, evidence is so limited, especially in preclinical studies. We aimed to investigate the effect of Psilocybe cubensis extract on posttraumatic stress disorder (PTSD)-like behavior, pain perception, locomotor activity, and anxiety in a rat model of PTSD. Male rats were exposed to three consecutive shocks (0.8 mA, 3 s interval) paired with three sounds broadcasted 3 s before delivering shocks (75 dB, 3 s). After 1, 3, or 21 days, freezing rate was measured in the fear-conditioning apparatus. Open filed test and hot plate were used to assess locomotor activity and anxiety, and pain subthreshold, respectively. Psilocybe cubensis was injected intraperitoneal at the dose of 25 mg/kg (single administration) before (pretrain) or after (posttrain) shocks, or before the test (pretest). Results showed psilocybin potently alleviated PTSD symptom is short- but not long-term after the induction of PTSD. Psilocybe cubensis decreased locomotor activity only in a short period after administration. Psilocybe cubensis also increased pain subthreshold and decreased anxiety. In conclusion, Psilocybe cubensis effects on PTSD-like behavior and locomotor activity seem to be remained in short-term, while Psilocybe cubensis effects on pain subthreshold and anxiety remained long-term. This is the first study evaluating the effect of Psilocybe cubensis on PTSD-like behavior in rats in three different time protocols (1, 3, and 21 days after fear conditioning). (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Altered functional connectivity between cortical networks associated with inhibitory control in trauma-exposed females.

Post-traumatic stress disorder (PTSD) is associated with impaired inhibitory control and alterations in large-scale brain network connectivity. However, few studies to date have examined the construct of inhibitory control as it relates to resting-state functional connectivity (rsFC) in a population with PTSD or trauma-exposure. The present study investigated the relationship between impaired inhibitory control and rsFC within the default mode network (DMN), central executive network (CEN), and salience network (SN) in a sample of females exposed to interpersonal trauma with and without PTSD (n = 67). Participants completed a classic Color-Word Stroop task as a measure of inhibitory control and two resting-state fMRI scans. We conducted voxelwise rsFC analyses with seed regions in the DMN, CEN, and SN and voxelwise linear regression analyses to examine the relationship between inhibitory control and rsFC of these networks across the sample. Better Stroop performance was negatively associated with total self-reported PTSD symptoms. An analysis of PTSD symptom clusters indicated that better Stroop performance was also associated with re-experiencing and hyperarousal symptoms, but not avoidance PTSD symptoms. Decreased coupling between the CEN and the DMN was associated with better inhibitory control in this sample of trauma-exposed females. These findings lend support to the hypothesis that efficient switching between these networks may contribute to better performance on cognitive and attentional tasks in trauma-exposed individuals.

Impact of depression and post-traumatic stress on manual and oculomotor performance in service members with a history of mild TBI.

OBJECTIVE: To determine the impact of depression and post-traumatic stress on an automated oculomotor and manual measure of visual attention, compared to conventional neuropsychological assessment. Setting: Military traumatic brain injury (TBI) rehabilitation program. PARTICIPANTS: 188 Active Duty Service Members (ADSM) with a history of mild TBI. DESIGN: A cross-sectional and correlational study with data obtained through an IRB-approved data registry study. Main measures: Bethesda Eye & Attention Measure (BEAM); brief neuropsychological battery; self-reported symptom surveys including Neurobehavioral Symptom Inventory (NSI), Patient Health Questionnaire-8 (PHQ-8), and PTSD Checklist-5 (PCL-5). RESULTS: Small effect sizes were found for partial correlations between both depression and post-traumatic stress and key BEAM metrics. In contrast, small-to-medium effects sizes were found across all traditional neuropsychological test measures. CONCLUSION: This study illustrates the profile of impairments associated with depression and post-traumatic stress on saccadic eye movements and manual responses to BEAM relative to conventional neuropsychological tests. Results demonstrated that among ADSM seen for mTBI, depression and PTS exert a significant negative impact on measures of processing speed, attention, executive function, and memory across saccadic, manual, and conventional neuropsychological tests. However, the unique psychometric features of each of these assessment approaches may assist in distinguishing the effects of psychiatric comorbidities within this population.

Bilateral eye movements disrupt the involuntary perceptual representation of trauma-related memories.

Bilateral eye movement (EM) is a critical component in eye movement desensitization and reprocessing (EMDR), an effective treatment for post-traumatic stress disorder. However, the role of bilateral EM in alleviating trauma-related symptoms is unclear. Here we hypothesize that bilateral EM selectively disrupts the perceptual representation of traumatic memories. We used the trauma film paradigm as an analog for trauma experience. Nonclinical participants viewed trauma films followed by a bilateral EM intervention or a static Fixation period as a control. Perceptual and semantic memories for the film were assessed with different measures. Results showed a significant decrease in perceptual memory recognition shortly after the EM intervention and subsequently in the frequency and vividness of film-related memory intrusions across one week, relative to the Fixation condition. The EM intervention did not affect the explicit recognition of semantic memories, suggesting a dissociation between perceptual and semantic memory disruption. Furthermore, the EM intervention effectively reduced psychophysiological affective responses, including the skin conductance response and pupil size, to film scenes and subjective affective ratings of film-related intrusions. Together, bilateral EMs effectively reduce the perceptual representation and affective response of trauma-related memories. Further theoretical developments are needed to elucidate the mechanism of bilateral EMs in trauma treatment.

A Ventromedial Prefrontal-to-Lateral Entorhinal Cortex Pathway Modulates the Gain of Behavioral Responding During Threat.

BACKGROUND: The ability to correctly associate cues and contexts with threat is critical for survival, and the inability to do so can result in threat-related disorders such as posttraumatic stress disorder. The prefrontal cortex (PFC) and hippocampus are well known to play critical roles in cued and contextual threat memory processing. However, the circuits that mediate prefrontal-hippocampal modulation of context discrimination during cued threat processing are less understood. Here, we demonstrate the role of a previously unexplored projection from the ventromedial region of PFC (vmPFC) to the lateral entorhinal cortex (LEC) in modulating the gain of behavior in response to contextual information during threat retrieval and encoding. METHODS: We used optogenetics followed by in vivo calcium imaging in male C57/B6J mice to manipulate and monitor vmPFC-LEC activity in response to threat-associated cues in different contexts. We then investigated the inputs to, and outputs from, vmPFC-LEC cells using Rabies tracing and channelrhodopsin-assisted electrophysiology. RESULTS: vmPFC-LEC cells flexibly and bidirectionally shaped behavior during threat expression, shaping sensitivity to contextual information to increase or decrease the gain of behavioral output in response to a threatening or neutral context, respectively. CONCLUSIONS: Glutamatergic vmPFC-LEC cells are key players in behavioral gain control in response to contextual information during threat processing and may provide a future target for intervention in threat-based disorders.

The Neurophysiology Behind Trauma-Focused Therapy Modalities Used to Treat Post-Traumatic Stress Disorder Across the Life Course: A Systematic Review.

This review presents the current state of understanding of trauma-informed modalities in light of current research in neuroscience, analyzing which brain structures and processes are impacted by these modalities. Studies included in the present review met the inclusion criteria of 1) addressing post-traumatic stress disorder (PTSD) in a specific population, 2) treatment of PTSD using any of the evidence-based trauma-informed modalities considered in this review, and 3) presenting functional magnetic resonance imagery (fMRI) data, derived from BOLD signals and voxel-compression maps, of brain structures impacted by these trauma-informed modalities. Articles for this review were collated through PubMed and MEDLINE, using key terms in descending order, such as 'childhood trauma', 'adolescent trauma', and 'adulthood trauma', to 'PTSD', 'fMRI', and so on, depending on the modality in question. Based on these criteria and research methods, 37 studies remained for inclusion in the present review. Among a number of critical findings, this review demonstrates that eye movement desensitization and reprocessing (EMDR) and mindfulness therapy effectively deactivate hindbrain regions implicated in the downregulation of autonomic nervous system (ANS) hyperarousal. This review also shows that trauma-focused cognitive behavioral therapy (TF-CBT) and EMDR activate the hippocampus, anterior cingulate cortex (ACC), medial prefrontal cortex (mPFC), and orbitofrontal cortex (OFC)-areas that are implicated in crucial cognitive, affective, and behavioral processes that aid trauma survivors in navigating their challenges.