Digital Interventions to Understand and Mitigate Stress Response: Protocol for Process and Content Evaluation of a Cohort Study.

BACKGROUND: Staffing and resource shortages, especially during the COVID-19 pandemic, have increased stress levels among health care workers. Many health care workers have reported feeling unable to maintain the quality of care expected within their profession, which, at times, may lead to moral distress and moral injury. Currently, interventions for moral distress and moral injury are limited. OBJECTIVE: This study has the following aims: (1) to characterize and reduce stress and moral distress related to decision-making in morally complex situations using a virtual reality (VR) scenario and a didactic intervention; (2) to identify features contributing to mental health outcomes using wearable, physiological, and self-reported questionnaire data; and (3) to create a personal digital phenotype profile that characterizes stress and moral distress at the individual level. METHODS: This will be a single cohort, pre- and posttest study of 100 nursing professionals in Ontario, Canada. Participants will undergo a VR simulation that requires them to make morally complex decisions related to patient care, which will be administered before and after an educational video on techniques to mitigate distress. During the VR session, participants will complete questionnaires measuring their distress and moral distress, and physiological data (electrocardiogram, electrodermal activity, plethysmography, and respiration) will be collected to assess their stress response. In a subsequent 12-week follow-up period, participants will complete regular assessments measuring clinical outcomes, including distress, moral distress, anxiety, depression, and loneliness. A wearable device will also be used to collect continuous data for 2 weeks before, throughout, and for 12 weeks after the VR session. A pre-post comparison will be conducted to analyze the effects of the VR intervention, and machine learning will be used to create a personal digital phenotype profile for each participant using the physiological, wearable, and self-reported data. Finally, thematic analysis of post-VR debriefing sessions and exit interviews will examine reoccurring codes and overarching themes expressed across participants' experiences. RESULTS: The study was funded in 2022 and received research ethics board approval in April 2023. The study is ongoing. CONCLUSIONS: It is expected that the VR scenario will elicit stress and moral distress. Additionally, the didactic intervention is anticipated to improve understanding of and decrease feelings of stress and moral distress. Models of digital phenotypes developed and integrated with wearables could allow for the prediction of risk and the assessment of treatment responses in individuals experiencing moral distress in real-time and naturalistic contexts. This paradigm could also be used in other populations prone to moral distress and injury, such as military and public safety personnel. TRIAL REGISTRATION: ClinicalTrials.gov NCT05923398; https://clinicaltrials.gov/study/NCT05923398. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/54180.

A tale of two targets: examining the differential effects of posterior cingulate cortex- and amygdala-targeted fMRI-neurofeedback in a PTSD pilot study.

Introduction: Real-time fMRI-based neurofeedback (rt-fMRI-NFB) is a non-invasive technology that enables individuals to self-regulate brain activity linked to neuropsychiatric symptoms, including those associated with post-traumatic stress disorder (PTSD). Selecting the target brain region for neurofeedback-mediated regulation is primarily informed by the neurobiological characteristics of the participant population. There is a strong link between PTSD symptoms and multiple functional disruptions in the brain, including hyperactivity within both the amygdala and posterior cingulate cortex (PCC) during trauma-related processing. As such, previous rt-fMRI-NFB studies have focused on these two target regions when training individuals with PTSD to regulate neural activity. However, the differential effects of neurofeedback target selection on PTSD-related neural activity and clinical outcomes have not previously been investigated. Methods: Here, we compared whole-brain activation and changes in PTSD symptoms between PTSD participants (n = 28) that trained to downregulate activity within either the amygdala (n = 14) or the PCC (n = 14) while viewing personalized trauma words. Results: For the PCC as compared to the amygdala group, we observed decreased neural activity in several regions implicated in PTSD psychopathology - namely, the bilateral cuneus/precuneus/primary visual cortex, the left superior parietal lobule, the left occipital pole, and the right superior temporal gyrus/temporoparietal junction (TPJ) - during target region downregulation using rt-fMRI-NFB. Conversely, for the amygdala as compared to the PCC group, there were no unique (i.e., over and above that of the PCC group) decreases in neural activity. Importantly, amygdala downregulation was not associated with significantly improved PTSD symptoms, whereas PCC downregulation was associated with reduced reliving and distress symptoms over the course of this single training session. In this pilot analysis, we did not detect significant between-group differences in state PTSD symptoms during neurofeedback. As a critical control, the PCC and amygdala groups did not differ in their ability to downregulate activity within their respective target brain regions. This indicates that subsequent whole-brain neural activation results can be attributed to the effects of the neurofeedback target region selection in terms of neurophysiological function, rather than as a result of group differences in regulatory success. Conclusion: In this study, neurofeedback-mediated downregulation of the PCC was differentially associated with reduced state PTSD symptoms and simultaneous decreases in PTSD-associated brain activity during a single training session. This novel analysis may guide researchers in choosing a neurofeedback target region in future rt-fMRI-NFB studies and help to establish the clinical efficacy of specific neurofeedback targets for PTSD. A future multi-session clinical trial of rt-fMRI-NFB that directly compares between PCC and amygdala target regions is warranted.

'I am afraid you will see the stain on my soul': Direct gaze neural processing in individuals with PTSD after moral injury recall.

Direct eye contact is essential to understanding others' thoughts and feelings in social interactions. However, those with post-traumatic stress disorder (PTSD) and exposure to moral injury (MI) may exhibit altered theory-of-mind (ToM)/mentalizing processes and experience shame which precludes one's capacity for direct eye contact. We investigated blood oxygenation level-dependent (BOLD) responses associated with direct vs averted gaze using a virtual reality paradigm in individuals with PTSD (n = 28) relative to healthy controls (n = 18) following recall of a MI vs a neutral memory. Associations between BOLD responses and clinical symptomatology were also assessed. After MI recall, individuals with PTSD showed greater activation in the right temporoparietal junction as compared to controls (T = 4.83; pFDR < 0.001; k = 237) during direct gaze. No significant activation occurred during direct gaze after neutral memory recall. Further, a significant positive correlation was found between feelings of distress and right medial superior frontal gyrus activation in individuals with PTSD (T = 5.03; pFDR = 0.049; k = 123). These findings suggest that direct gaze after MI recall prompts compensatory ToM/mentalizing processing. Implications for future interventions aimed at mitigating the effects of PTSD on social functioning are discussed.

Moral Distress, Mental Health, and Risk and Resilience Factors Among Military Personnel Deployed to Long-Term Care Facilities During the COVID-19 Pandemic: Research Protocol and Participation Metrics.

BACKGROUND: The earliest days of the COVID-19 pandemic in Canada were marked by a significant surge in COVID-19 cases and COVID-19-related deaths among residents of long-term care facilities (LTCFs). As part of Canada's response to the COVID-19 pandemic, Canadian Armed Forces (CAF) personnel were mobilized for an initial emergency domestic deployment to the hardest-hit LTCFs (Operation LASER LTCF) to support the remaining civilian staff in ensuring the continued delivery of care to residents. Akin to what was observed following past CAF international humanitarian missions, there was an expected increased risk of exposure to multiple stressors that may be psychologically traumatic and potentially morally injurious in nature (ie, related to core values, eg, witnessing human suffering). Emerging data from health care workers exposed to the unprecedented medical challenges and dilemmas of the early pandemic stages also indicated that such experiences were associated with increased risk of adverse mental health outcomes. OBJECTIVE: This study aims to identify and quantify the individual-, group-, and organizational-level risk and resilience factors associated with moral distress, moral injury, and traditional mental health and well-being outcomes of Operation LASER LTCF CAF personnel. This paper aimed to document the methodology, implementation procedures, and participation metrics. METHODS: A multimethod research initiative was conducted consisting of 2 primary data collection studies (a quantitative survey and qualitative interviews). The quantitative arm was a complete enumeration survey with web-based, self-report questionnaires administered at 3 time points (3, 6, and 12 mo after deployment). The qualitative arm consisted of individual, web-based interviews with a focus on understanding the nuanced lived experiences of individuals participating in the Operation LASER LTCF deployment. RESULTS: CAF personnel deployed to Operation LASER LTCF (N=2595) were invited to participate in the study. Data collection is now complete. Overall, of the 2595 deployed personnel, 1088 (41.93%), 582 (22.43%), and 497 (19.15%) responded to the survey at time point 1 (3 mo), time point 2 (6 mo), and time point 3 (12 mo) after deployment, respectively. The target sample size for the qualitative interviews was set at approximately 50 considering resourcing and data saturation. Interest in participating in qualitative interviews surpassed expectations, with >200 individuals expressing interest; this allowed for purposive sampling across key characteristics, including gender, rank, Operation LASER LTCF role, and province. In total, 53 interviews were conducted. CONCLUSIONS: The data generated through this research have the potential to inform and promote better understanding of the well-being and mental health of Operation LASER LTCF personnel over time; identify general and Operation LASER LTCF-specific risk and protective factors; provide necessary support to the military personnel who served in this mission; and inform preparation and interventions for future missions, especially those more domestic and humanitarian in nature. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/44299.

A randomized controlled trial of Deep Brain Reorienting: a neuroscientifically guided treatment for post-traumatic stress disorder.

BACKGROUND: Advanced neuroscientific insights surrounding post-traumatic stress disorder (PTSD) and its associated symptomatology should beget psychotherapeutic treatments that integrate these insights into practice. Deep Brain Reorienting (DBR) is a neuroscientifically-guided psychotherapeutic intervention that targets the brainstem-level neurophysiological sequence that transpired during a traumatic event. Given that contemporary treatments have non-response rates of up to 50% and high drop-out rates of >18%, DBR is investigated as a putative candidate for effective treatment of some individuals with PTSD. OBJECTIVE: To conduct an interim evaluation of the effectiveness of an eight-session clinical trial of videoconference-based DBR versus waitlist (WL) control for individuals with PTSD. METHOD: Fifty-four individuals with PTSD were randomly assigned to DBR (N = 29) or WL (N = 25). At baseline, post-treatment, and three-month follow-up, participants' PTSD symptom severity was assessed using the Clinician Administered PTSD Scale (CAPS-5). This is an interim analysis of a clinical trial registered with the U. S. National Institute of Health (NCT04317820). RESULTS: Significant between-group differences in CAPS-total and all subscale scores (re-experiencing, avoidance, negative alterations in cognitions/mood, alterations in arousal/reactivity) were found at post-treatment (CAPS-total: Cohen's d = 1.17) and 3-month-follow-up (3MFU) (CAPS-total: Cohen's d = 1.18). Significant decreases in CAPS-total and all subscale scores were observed within the DBR group pre - to post-treatment (36.6% CAPS-total reduction) and pre-treatment to 3MFU (48.6% CAPS-total reduction), whereas no significant decreases occurred in the WL group. After DBR, 48.3% at post-treatment and 52.0% at 3MFU no longer met PTSD criteria. Attrition was minimal with one participant not completing treatment; eight participants were lost to 3MFU. CONCLUSIONS: These findings provide emerging evidence for the effectiveness of DBR as a well-tolerated treatment that is based on theoretical advances highlighting alterations to subcortical mechanisms in PTSD and associated symptomatology. Additional research utilizing larger sample sizes, neuroimaging data, and comparisons or adjacencies with other psychotherapeutic approaches is warranted.Trial registration: ClinicalTrials.gov identifier: NCT04317820..

First study to evaluate the effects of Deep Brain Reorienting (DBR) therapy on PTSD symptoms.Eight internet-based DBR sessions resulted in significant decreases in PTSD symptoms post-treatment and at 3-month follow-up in comparison to a waitlist group.Large effect sizes and a low drop-out rate suggest that DBR may be an effective, well-tolerated neuroscientifically guided treatment for PTSD.

How the body remembers: Examining the default mode and sensorimotor networks during moral injury autobiographical memory retrieval in PTSD.

Neural representations of sensory percepts and motor responses constitute key elements of autobiographical memory. However, these representations may remain as unintegrated sensory and motor fragments in traumatic memory, thus contributing toward re-experiencing and reliving symptoms in trauma-related conditions such as post-traumatic stress disorder (PTSD). Here, we investigated the sensorimotor network (SMN) and posterior default mode network (pDMN) using a group independent component analysis (ICA) by examining their functional connectivity during a script-driven memory retrieval paradigm of (potentially) morally injurious events in individuals with PTSD and healthy controls. Moral injury (MI), where an individual acts or fails to act in a morally aligned manner, is examined given its inherent ties to disrupted motor planning and thus sensorimotor mechanisms. Our findings revealed significant differences in functional network connectivity across the SMN and pDMN during MI retrieval in participants with PTSD (n = 65) as compared to healthy controls (n = 25). No such significant group-wise differences emerged during retrieval of a neutral memory. PTSD-related alterations included hyperconnectivity between the SMN and pDMN, enhanced within-network connectivity of the SMN with premotor areas, and increased recruitment of the supramarginal gyrus into both the SMN and the pDMN during MI retrieval. In parallel with these neuroimaging findings, a positive correlation was found between PTSD severity and subjective re-experiencing intensity ratings after MI retrieval. These results suggest a neural basis for traumatic re-experiencing, where reliving and/or re-enacting a past morally injurious event in the form of sensory and motor fragments occurs in place of retrieving a complete, past-contextualized narrative as put forth by Brewin and colleagues (1996) and Conway and Pleydell-Pearce (2000). These findings have implications for bottom-up treatments targeting directly the sensory and motoric elements of traumatic experiences.

Homeostatic normalization of alpha brain rhythms within the default-mode network and reduced symptoms in post-traumatic stress disorder following a randomized controlled trial of electroencephalogram neurofeedback.

Collective research has identified a key electroencephalogram signature in patients with post-traumatic stress disorder, consisting of abnormally reduced alpha (8-12 Hz) rhythms. We conducted a 20-session, double-blind, randomized controlled trial of alpha desynchronizing neurofeedback in patients with post-traumatic stress disorder over 20 weeks. Our objective was to provide mechanistic evidence underlying potential clinical improvements by examining changes in aberrant post-traumatic stress disorder brain rhythms (namely, alpha oscillations) as a function of neurofeedback treatment. We randomly assigned participants with a primary diagnosis of post-traumatic stress disorder (n = 38) to either an experimental group (n = 20) or a sham-control group (n = 18). A multichannel electroencephalogram cap was used to record whole-scalp resting-state activity pre- and post-neurofeedback treatment, for both the experimental and sham-control post-traumatic stress disorder groups. We first observed significantly reduced relative alpha source power at baseline in patients with post-traumatic stress disorder as compared to an age/sex-matched group of neurotypical healthy controls (n = 32), primarily within regions of the anterior default mode network. Post-treatment, we found that only post-traumatic stress disorder patients in the experimental neurofeedback group demonstrated significant alpha resynchronization within areas that displayed abnormally low alpha power at baseline. In parallel, we observed significantly decreased post-traumatic stress disorder severity scores in the experimental neurofeedback group only, when comparing baseline to post-treatment (Cohen's d = 0.77) and three-month follow-up scores (Cohen's d = 0.75), with a remission rate of 60.0% at the three-month follow-up. Overall, our results indicate that neurofeedback training can rescue pathologically reduced alpha rhythmicity, a functional biomarker that has repeatedly been linked to symptoms of hyperarousal and cortical disinhibition in post-traumatic stress disorder. This randomized controlled trial provides long-term evidence suggesting that the 'alpha rebound effect' (i.e. homeostatic alpha resynchronization) occurs within key regions of the default mode network previously implicated in post-traumatic stress disorder.

Investigating TSPO levels in occupation-related posttraumatic stress disorder.

Microglia are immune brain cells implicated in stress-related mental illnesses including posttraumatic stress disorder (PTSD). Their role in the pathophysiology of PTSD, and on neurobiological systems that regulate stress, is not completely understood. We tested the hypothesis that microglia activation, in fronto-limbic brain regions involved in PTSD, would be elevated in participants with occupation-related PTSD. We also explored the relationship between cortisol and microglia activation. Twenty participants with PTSD and 23 healthy controls (HC) completed positron emission tomography (PET) scanning of the 18-kDa translocator protein (TSPO), a putative biomarker of microglia activation using the probe [18F]FEPPA, and blood samples for measurement of cortisol. [18F]FEPPA VT was non-significantly elevated (6.5-30%) in fronto-limbic regions in PTSD participants. [18F]FEPPA VT was significantly higher in PTSD participants reporting frequent cannabis use compared to PTSD non-users (44%, p = 0.047). Male participants with PTSD (21%, p = 0.094) and a history of early childhood trauma (33%, p = 0.116) had non-significantly higher [18F]FEPPA VT. Average fronto-limbic [18F]FEPPA VT was positively related to cortisol (r = 0.530, p = 0.028) in the PTSD group only. Although we did not find a significant abnormality in TSPO binding in PTSD, findings suggest microglial activation might have occurred in a subgroup who reported frequent cannabis use. The relationship between cortisol and TSPO binding suggests a potential link between hypothalamic-pituitary-adrenal-axis dysregulation and central immune response to trauma which warrants further study.

Posterior cingulate cortex targeted real-time fMRI neurofeedback recalibrates functional connectivity with the amygdala, posterior insula, and default-mode network in PTSD.

BACKGROUND: Alterations within large-scale brain networks-namely, the default mode (DMN) and salience networks (SN)-are present among individuals with posttraumatic stress disorder (PTSD). Previous real-time functional magnetic resonance imaging (fMRI) and electroencephalography neurofeedback studies suggest that regulating posterior cingulate cortex (PCC; the primary hub of the posterior DMN) activity may reduce PTSD symptoms and recalibrate altered network dynamics. However, PCC connectivity to the DMN and SN during PCC-targeted fMRI neurofeedback remains unexamined and may help to elucidate neurophysiological mechanisms through which these symptom improvements may occur. METHODS: Using a trauma/emotion provocation paradigm, we investigated psychophysiological interactions over a single session of neurofeedback among PTSD (n = 14) and healthy control (n = 15) participants. We compared PCC functional connectivity between regulate (in which participants downregulated PCC activity) and view (in which participants did not exert regulatory control) conditions across the whole-brain as well as in a priori specified regions-of-interest. RESULTS: During regulate as compared to view conditions, only the PTSD group showed significant PCC connectivity with anterior DMN (dmPFC, vmPFC) and SN (posterior insula) regions, whereas both groups displayed PCC connectivity with other posterior DMN areas (precuneus/cuneus). Additionally, as compared with controls, the PTSD group showed significantly greater PCC connectivity with the SN (amygdala) during regulate as compared to view conditions. Moreover, linear regression analyses revealed that during regulate as compared to view conditions, PCC connectivity to DMN and SN regions was positively correlated to psychiatric symptoms across all participants. CONCLUSION: In summary, observations of PCC connectivity to the DMN and SN provide emerging evidence of neural mechanisms underlying PCC-targeted fMRI neurofeedback among individuals with PTSD. This supports the use of PCC-targeted neurofeedback as a means by which to recalibrate PTSD-associated alterations in neural connectivity within the DMN and SN, which together, may help to facilitate improved emotion regulation abilities in PTSD.

Cortical Gyrification Morphology in Adult Males with Mild Traumatic Brain Injury.

Cortical gyrification, as a specific measure derived from magnetic resonance imaging, remains understudied in mild traumatic brain injury (mTBI). Local gyrification index (lGI) and mean curvature are related measures indexing the patterned folding of the cortex,ml which reflect distinct properties of cortical morphology and geometry. Using both metrics, we examined cortical gyrification morphology in 59 adult males with mTBI (n = 29) versus those without (n = 30) mTBI in the subacute phase of injury (between 2 weeks and 3 months). The effect of IQ on lGI and brain-symptom relations were also examined. General linear models revealed greater lGI in mTBI versus controls in the frontal lobes bilaterally, but reduced lGI in mTBI of the left temporal lobe. An age-related decrease in lGI was found in numerous areas, with no significant group-by-age interaction effects observed. Including other factors (i.e., mTBI severity, symptoms, and IQ) in the lGI model yielded similar results with few exceptions. Mean curvature analyses depicted a significant group-by-age interaction with the absence of significant main effects of group or age. Our results suggest that cortical gyrification morphology is adversely affected by mTBI in both frontal and temporal lobes, which are thought of as highly susceptible regions to mTBI. These findings contribute to understanding the effects of mTBI on neuromorphological properties, such as alterations in cortical gyrification, which reflect underlying microstructural changes (i.e., apoptosis, neuronal number, or white matter alterations). Future studies are needed to infer causal relationships between micro- and macrostructural changes after an mTBI and investigate potential sex differences.

A Distinct Metabolite Signature in Military Personnel Exposed to Repetitive Low-Level Blasts.

Military Breachers and Range Staff (MBRS) are subjected to repeated sub-concussive blasts, and they often report symptoms that are consistent with a mild traumatic brain injury (mTBI). Biomarkers of blast injury would potentially aid blast injury diagnosis, surveillance and avoidance. Our objective was to identify plasma metabolite biomarkers in military personnel that were exposed to repeated low-level or sub-concussive blast overpressure. A total of 37 military members were enrolled (18 MBRS and 19 controls), with MBRS having participated in 8-20 breaching courses per year, with a maximum exposure of 6 blasts per day. The two cohorts were similar except that the number of blast exposures were significantly higher in the MBRS, and the MBRS cohort suffered significantly more post-concussive symptoms and poorer health on assessment. Metabolomics profiling demonstrated significant differences between groups with 74% MBRS classification accuracy (CA). Feature reduction identified 6 metabolites that resulted in a MBRS CA of 98%, and included acetic acid (23.7%), formate (22.6%), creatine (14.8%), acetone (14.2%), methanol (12,7%), and glutamic acid (12.0%). All 6 metabolites were examined with individual receiver operating characteristic (ROC) curve analyses and demonstrated areas-under-the-curve (AUCs) of 0.82-0.91 (P ≤ 0.001) for MBRS status. Several parsimonious combinations of three metabolites increased accuracy of ROC curve analyses to AUCs of 1.00 (P < 0.001), while a combination of volatile organic compounds (VOCs; acetic acid, acetone and methanol) yielded an AUC of 0.98 (P < 0.001). Candidate biomarkers for chronic blast exposure were identified, and if validated in a larger cohort, may aid surveillance and care of military personnel. Future point-of-care screening could be developed that measures VOCs from breath, with definitive diagnoses confirmed with plasma metabolomics profiling.

Conducting research during the COVID-19 pandemic: the Op LASER study. / Mener des recherches au cours de la pandémie de COVID-19 : l'étude sur l'Opération LASER.

The Canadian Armed Forces (CAF) deployed 2595 regular and reserve force personnel on Operation (Op) LASER, the CAF's mission to provide support to civilian staff at longterm care facilities in Ontario and in the Centres d'hébergement de soins de longue durée in Quebec. An online longitudinal survey and in-depth virtual discussions were conducted by a multidisciplinary team of researchers with complementary expertise. This paper highlights the challenges encountered in conducting this research and their impact on the design and implementation of the study, and provides lessons learned that may be useful to researchers responding to similar public health crises in the future.

There are a number of challenges involved in conducting longitudinal research in an applied military setting during a global public health crisis such as the COVID-19 pandemic. These challenges include but are not limited to a sudden transition to a distributed remote work environment, tight timelines, the need to obtain approvals from different agencies and departments, having to prioritize multiple study objectives, and survey fatigue. To overcome these challenges in future public health crises, it is important to (1) develop and maintain collaborative networks across government, academia and industry; (2) develop a standard set of pre-deployment demographic and health indicators to establish a baseline; and (3) use mixed methods approaches for a richer understanding of mental health trajectories following stressful events.

La réalisation d'une enquête longitudinale dans un contexte militaire concret pendant une crise mondiale de santé publique, comme la pandémie de COVID-19, vient avec son lot de défis. Parmi ces défis, on peut relever une transition subite vers un environnement de travail à distance, des délais serrés, la nécessité d'obtenir des approbations de différents organismes et ministères, la nécessité de prioriser plusieurs objectifs d'étude et la lassitude à l'égard des enquêtes. Pour relever ces défis au cours des futures crises de santé publique, il sera essentiel : 1) de créer et d'entretenir des réseaux de collaboration qui relieront le gouvernement, le milieu universitaire et les divers secteurs d'activité, 2) de créer un ensemble normalisé d'indicateurs démographiques et sanitaires avant le déploiement, en vue de l'obtention de données de référence et 3) de recourir à des méthodes mixtes pour mieux comprendre les trajectoires en matière de santé mentale à la suite d'événements stressants.

Moral wounds run deep: exaggerated midbrain functional network connectivity across the default mode network in posttraumatic stress disorder.

BACKGROUND: A moral injury occurs when a deeply held moral code has been violated, and it can lead to the development of symptoms of posttraumatic stress disorder (PTSD). However, the neural correlates that differentiate moral injury and PTSD remain largely unknown. Intrinsic connectivity networks such as the default mode network (DMN) appear to be altered in people with PTSD who have experienced moral injury. However, brainstem, midbrain and cerebellar systems are rarely integrated into the intrinsic connectivity networks; this is a critical oversight, because these systems display marked differences in people with PTSD and are thought to underlie strong moral emotions such as shame, guilt and betrayal. METHODS: We conducted an independent component analysis on data generated during script-driven memory recall of moral injury in participants with military- or law enforcement-related PTSD (n = 28), participants with civilian-related PTSD (n = 28) and healthy controls exposed to a potentially morally injurious event (n = 18). We conducted group-wise comparisons of functional network connectivity differences across a DMN-correlated independent component, with a particular focus on brainstem, midbrain and cerebellar systems. RESULTS: We found stronger functional network connectivity in the midbrain periaqueductal grey (t 71 = 4.95, p FDR = 0.028, k = 39) and cerebellar lobule IX (t 71 = 4.44, p FDR = 0.046, k = 49) in participants with civilian-related PTSD as compared to healthy controls. We also found a trend toward stronger functional network connectivity in the midbrain periaqueductal grey (t 71 = 4.22, p FDR = 0.076, k = 60) in participants with military- or law enforcement-related PTSD as compared to healthy controls. LIMITATIONS: The significant clusters were large, but resolution is generally lower for subcortical structures. CONCLUSION: In PTSD, the DMN appears to be biased toward lower-level, midbrain systems, which may drive toxic shame and related moral emotions that are common in PTSD, highlighting the depth at which moral injuries are represented neurobiologically.

Well-being of Canadian Veterans during the COVID-19 pandemic: cross-sectional results from the COVID-19 Veteran well-being study.

Background: The impacts of the COVID-19 pandemic have disproportionally affected different population groups. Veterans are more likely to have pre-existing mental health conditions compared to the general Canadian population, experience compounded stressors resulting from disruptions to familial, social, and occupational domains, and were faced with changes in health-care delivery (e.g. telehealth). The objectives of this study are to assess (a) the mental health impact of COVID-19 and related life changes on the well-being of Veterans and (b) perceptions of and satisfaction with changes in health-care treatments and delivery during the pandemic. Methods: A total of 1136 Canadian Veterans participated in an online survey. Participants completed questions pertaining to their mental health and well-being, lifestyle changes, and concerns relating to the COVID-19 pandemic, as well as experiences and satisfaction with health-care treatments during the pandemic. Results: Results showed that 55.9% of respondents reported worse mental health functioning compared to before the pandemic. The frequency of probable posttraumatic stress disorder, major depressive disorder, generalized anxiety disorder, alcohol use disorder, and suicidal ideation were 34.2%, 35.3%, 26.8%, 13.0%, and 22.0%, respectively. Between 38.6% and 53.1% of respondents attributed their symptoms as either directly related to or exacerbated by the pandemic. Approximately 18% of respondents reported using telehealth for mental health services during the pandemic, and among those, 72.8% indicated a choice to use telehealth even after the pandemic. Conclusions: This study found that Veterans experienced worsening mental health as a result of the COVID-19 pandemic. The use of telehealth services was widely endorsed by mental health treatment-seeking Veterans who transitioned to virtual care during the pandemic. Our findings have important clinical and programmeadministrator implications, emphasizing the need to reach out to support veterans, especially those with pre-existing mental health conditions and to enhance and maintain virtual care even post-pandemic.

Antecedentes: Los impactos de la pandemia del COVID-19 han afectado de manera desproporcionada a diferentes grupos de la población. Los veteranos tienen más probabilidades de tener afecciones de salud mental preexistentes en comparación con la población canadiense en general, experimentar factores estresantes agravados como resultado de las interrupciones en los dominios familiares, sociales, y ocupacionales, y se enfrentan a cambios en la prestación de la atención médica (por ejemplo, telesalud). Los objetivos de este estudio son evaluar (a) el impacto en la salud mental del COVID-19 y los cambios de vida relacionados en el bienestar de los Veteranos y (b) las percepciones y la satisfacción con los cambios en los tratamientos y la entrega de la atención médica durante la pandemia.Métodos: Un total de 1136 veteranos canadienses participaron en una encuesta en línea. Los participantes completaron preguntas relacionadas con su salud mental y bienestar, cambios en el estilo de vida, e inquietudes relacionadas con la pandemia del COVID-19, así como experiencias y satisfacción con los tratamientos de atención médica durante la pandemia.Resultados: Los resultados mostraron que el 55,9% de los encuestados informaron un peor funcionamiento de la salud mental en comparación con antes de la pandemia. La frecuencia de probable trastorno de estrés postraumático, trastorno depresivo mayor, trastorno de ansiedad generalizada, trastorno por consumo de alcohol, e ideación suicida fue del 34,2%, 35,3%, 26,8%, 13,0% y 22,0%, respectivamente. Entre el 38,6% y el 53,1% de los encuestados atribuyeron sus síntomas como directamente relacionados con la pandemia o agravados por ella. Aproximadamente el 18% de los encuestados informó haber utilizado la telesalud para los servicios de salud mental durante la pandemia, y entre ellos, el 72,8% indicó que había optado por utilizar la telesalud incluso después de la pandemia.Conclusiones: Este estudio encontró que los Veteranos experimentaron un empeoramiento de la salud mental como resultado de la pandemia del COVID-19. El uso de los servicios de telesalud fue ampliamente respaldado por los Veteranos en busca de tratamiento de salud mental que hicieron la transición a la atención virtual durante la pandemia. Nuestros hallazgos tienen importantes implicaciones clínicas y para los administradores de programas, enfatizando la necesidad de ayudar a los veteranos, especialmente a aquellos con condiciones de salud mental preexistentes, y de mejorar y mantener la atención virtual incluso después de una pandemia.

Pathways to mental health care in active military populations across the Five-Eyes nations: An integrated perspective.

Military service is associated with increased risk of mental health problems. Previous reviews have pointed to under-utilization of mental health services in military populations. Building on the most recent systematic review, our narrative, critical review takes a complementary approach and considers research across the Five-Eyes nations from the past six years to update and broaden the discussion on pathways to mental healthcare in military populations. We find that at a broad population level, there is improvement in several indicators of mental health care access, with greater gains in initial engagement, time to first treatment contact, and subjective satisfaction with care, and smaller gains in objective indicators of adequacy of care. Among individual-level barriers to care-seeking, there is progress in improving recognition of need for care and reducing stigma concerns. Among organizational-level barriers, there are advances in availability of services and cultural acceptance of care-seeking. Other barriers, such as concerns around confidentiality, career impact, and deployability persist, however, and may account for some remaining unmet need. To address these barriers, new initiatives that are more evidence-based, theoretically-driven, and culturally-sensitive, are therefore needed, and must be rigorously evaluated to ensure they bring about additional improvements in pathways to care.

Imaging of astrocytes in posttraumatic stress disorder: A PET study with the monoamine oxidase B radioligand [11C]SL25.1188.

Posttraumatic stress disorder (PTSD) is a debilitating mental health condition that results from exposure to traumatic event(s). Decreased astrocyte-related proteins (e.g., glial fibrillary acidic protein, GFAP) and atrophic astrocytes in corticolimbic brain areas implicated in PTSD have been reported in experimental models suggesting that astrocyte pathology may be a feature of this disorder. We used positron emission tomography (PET) of the monoamine oxidase (MAO)-B probe [11C]SL25.1188 to test the hypothesis that levels of MAO-B, an index of astrocyte levels is decreased in PTSD. MAO-B availability ([11C]SL25.1188 distribution volume) was measured in 13 participants with PTSD (∼39 years, 6F) and 17 healthy controls (HC) (∼31 years, 9F). A magnetic resonance image was acquired to delineate 6 cortiolimbic brain regions. PTSD was associated with a trending reduction in [11C]SL25.1188 availability across regions (8-17%; p = 0.067) implicating the ventral striatum (p uncorrected = 0.015) and medial prefrontal cortex (p uncorrected = 0.060). [11C]SL25.1188 availability was ∼30% lower in corticolimbic regions in PTSD with co-morbid major depressive disorder (MDD) (n = 4) vs HC (p = 0.001) and vs PTSD without MDD (p = 0.005). Our preliminary results do not suggest astrogliosis (inferred from elevated availability) in PTSD, but rather point to a loss of astrocytes or an independent downregulation of MAO-B in PTSD with more severe negative affect. These exploratory findings, which are partly in line with preclinical literature and recent PET observations of decreased microglia marker, Translocator Protein, in PTSD, warrant replication in a larger PTSD cohort.

Differential mechanisms of posterior cingulate cortex downregulation and symptom decreases in posttraumatic stress disorder and healthy individuals using real-time fMRI neurofeedback.

BACKGROUND: Intrinsic connectivity networks, including the default mode network (DMN), are frequently disrupted in individuals with posttraumatic stress disorder (PTSD). The posterior cingulate cortex (PCC) is the main hub of the posterior DMN, where the therapeutic regulation of this region with real-time fMRI neurofeedback (NFB) has yet to be explored. METHODS: We investigated PCC downregulation while processing trauma/stressful words over 3 NFB training runs and a transfer run without NFB (total n = 29, PTSD n = 14, healthy controls n = 15). We also examined the predictive accuracy of machine learning models in classifying PTSD versus healthy controls during NFB training. RESULTS: Both the PTSD and healthy control groups demonstrated reduced reliving symptoms in response to trauma/stressful stimuli, where the PTSD group additionally showed reduced symptoms of distress. We found that both groups were able to downregulate the PCC with similar success over NFB training and in the transfer run, although downregulation was associated with unique within-group decreases in activation within the bilateral dmPFC, bilateral postcentral gyrus, right amygdala/hippocampus, cingulate cortex, and bilateral temporal pole/gyri. By contrast, downregulation was associated with increased activation in the right dlPFC among healthy controls as compared to PTSD. During PCC downregulation, right dlPFC activation was negatively correlated to PTSD symptom severity scores and difficulties in emotion regulation. Finally, machine learning algorithms were able to classify PTSD versus healthy participants based on brain activation during NFB training with 80% accuracy. CONCLUSIONS: This is the first study to investigate PCC downregulation with real-time fMRI NFB in both PTSD and healthy controls. Our results reveal acute decreases in symptoms over training and provide converging evidence for EEG-NFB targeting brain networks linked to the PCC.

Well-being of Canadian Armed Forces Veterans and Spouses of Veterans During the COVID-19 Pandemic: Protocol for a Prospective Longitudinal Survey.

BACKGROUND: The COVID-19 pandemic has resulted in significant changes to everyday life, including social distancing mandates, changes to health care, and a heightened risk of infection. Previous research has shown that Canadian Armed Forces (CAF) veterans are at higher risk of developing mental and physical health conditions. Veterans and their families may face unique social challenges that can compound with pandemic-related disruptions to negatively impact well-being. OBJECTIVE: This study aims to longitudinally characterize the mental health of CAF veterans and spouses of CAF veterans throughout the pandemic and to understand the dynamic influences of pandemic-related stressors on psychological health over time. METHODS: We employed a prospective longitudinal panel design using an online data collection platform. Study participation was open to all CAF veterans and spouses of CAF veterans residing in Canada. Participants were asked to complete a comprehensive battery of assessments representing psychological well-being, chronic pain, health care access patterns, physical environment, employment, social integration, and adjustment to pandemic-related lifestyle changes. Follow-up assessments were conducted every 3 months over an 18-month period. This study was approved by the Western University Health Sciences and Lawson Health Research Institute Research Ethics Boards. RESULTS: Baseline data were collected between July 2020 and February 2021. There were 3 population segments that participated in the study: 1047 veterans, 366 spouses of veterans, and 125 veterans who are also spouses of veterans completed baseline data collection. As of November 2021, data collection is ongoing, with participants completing the 9- or 12-month follow-up surveys depending on their date of self-enrollment. Data collection across all time points will be complete in September 2022. CONCLUSIONS: This longitudinal survey is unique in its comprehensive assessment of domains relevant to veterans and spouses of veterans during the COVID-19 pandemic, ranging from occupational, demographic, social, mental, and physical domains, to perceptions and experiences with health care treatments and access. The results of this study will be used to inform policy for veteran and veteran family support, and to best prepare for similar emergencies should they occur in the future. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/34984.