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.

Adverse Life Experiences and Brain Function: A Meta-Analysis of Functional Magnetic Resonance Imaging Findings.

Importance: Adverse life experiences have been proposed to contribute to diverse mental health problems through an association with corticolimbic functioning. Despite compelling evidence from animal models, findings from studies in humans have been mixed; activation likelihood estimation (ALE) meta-analyses have failed to identify a consistent association of adverse events with brain function. Objective: To investigate the association of adversity exposure with altered brain reactivity using multilevel kernel density analyses (MKDA), a meta-analytic approach considered more robust than ALE to small sample sizes and methodological differences between studies. Data Sources: Searches were conducted using PsycInfo, Medline, EMBASE, and Web of Science from inception through May 4, 2022. The following search term combinations were used for each database: trauma, posttraumatic stress disorder (PTSD), abuse, maltreatment, poverty, adversity, or stress; and functional magnetic resonance imaging (fMRI) or neuroimaging; and emotion, emotion regulation, memory, memory processing, inhibitory control, executive functioning, reward, or reward processing. Study Selection: Task-based fMRI studies within 4 domains (emotion processing, memory processing, inhibitory control, and reward processing) that included a measure of adverse life experiences and whole-brain coordinate results reported in Talairach or Montreal Neurological Institute space were included. Conference abstracts, books, reviews, meta-analyses, opinions, animal studies, articles not in English, and studies with fewer than 5 participants were excluded. Data Extraction and Synthesis: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guideline, 2 independent reviewers assessed abstracts and full-text articles for entry criteria. A third reviewer resolved conflicts and errors in data extraction. Data were pooled using a random-effects model and data analysis occurred from August to November 2022. Main Outcomes and Measures: Peak activation x-axis (left-right), y-axis (posterior-anterior), and z-axis (inferior-superior) coordinates were extracted from all studies and submitted to MKDA meta-analyses. Results: A total of 83 fMRI studies were included in the meta-analysis, yielding a combined sample of 5242 participants and 801 coordinates. Adversity exposure was associated with higher amygdala reactivity (familywise error rate corrected at P < .001; x-axis = 22; y-axis = -4; z-axis = -17) and lower prefrontal cortical reactivity (familywise error rate corrected at P < .001; x-axis = 10; y-axis = 60; z-axis = 10) across a range of task domains. These altered responses were only observed in studies that used adult participants and were clearest among those who had been exposed to severe threat and trauma. Conclusions and Relevance: In this meta-analysis of fMRI studies of adversity exposure and brain function, prior adversity exposure was associated with altered adult brain reactivity to diverse challenges. These results might better identify how adversity diminishes the ability to cope with later stressors and produces enduring susceptibility to mental health problems.

Machine learning models predict PTSD severity and functional impairment: A personalized medicine approach for uncovering complex associations among heterogeneous symptom profiles.

OBJECTIVE: Posttraumatic stress disorder (PTSD) is a debilitating psychiatric illness, experienced by approximately 10% of the population. Heterogeneous presentations that include heightened dissociation, comorbid anxiety and depression, and emotion dysregulation contribute to the severity of PTSD, in turn, creating barriers to recovery. There is an urgent need to use data-driven approaches to better characterize complex psychiatric presentations with the aim of improving treatment outcomes. We sought to determine if machine learning models could predict PTSD-related illness in a real-world treatment-seeking population using self-report clinical data. METHOD: Secondary clinical data from 2017 to 2019 included pretreatment measures such as trauma-related symptoms, other mental health symptoms, functional impairment, and demographic information from adults admitted to an inpatient unit for PTSD in Canada (n = 393). We trained two nonlinear machine learning models (extremely randomized trees) to identify predictors of (a) PTSD symptom severity and (b) functional impairment. We assessed model performance based on predictions in novel subsets of patients. RESULTS: Approximately 43% of the variance in PTSD symptom severity (R²avg = .43, R²median = .44, p = .001) was predicted by symptoms of anxiety, dissociation, depression, negative trauma-related beliefs about others, and emotion dysregulation. In addition, 32% of the variance in functional impairment scores (R²avg = .32, R²median = .33, p = .001) was predicted by anxiety, PTSD symptom severity, cognitive dysfunction, dissociation, and depressive symptoms. CONCLUSIONS: Our results reinforce that dissociation, cooccurring anxiety and depressive symptoms, maladaptive trauma appraisals, cognitive dysfunction, and emotion dysregulation are critical targets for trauma-related interventions. Machine learning models can inform personalized medicine approaches to maximize trauma recovery in real-world inpatient populations. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Altered Resting-State functional connectivity in the anterior and posterior hippocampus in Post-traumatic stress disorder: The central role of the anterior hippocampus.

BACKGROUND: Post-traumatic stress disorder can be viewed as a memory disorder, with trauma-related flashbacks being a core symptom. Given the central role of the hippocampus in autobiographical memory, surprisingly, there is mixed evidence concerning altered hippocampal functional connectivity in PTSD. We shed light on this discrepancy by considering the distinct roles of the anterior versus posterior hippocampus and examine how this distinction may map onto whole-brain resting-state functional connectivity patterns among those with and without PTSD. METHODS: We first assessed whole-brain between-group differences in the functional connectivity profiles of the anterior and posterior hippocampus within a publicly available data set of resting-state fMRI data from 31 male Vietnam war veterans diagnosed with PTSD (mean age = 67.6 years, sd = 2.3) and 29 age-matched combat-exposed male controls (age = 69.1 years, sd = 3.5). Next, the connectivity patterns of each subject within the PTSD group were correlated with their PTSD symptom scores. Finally, the between-group differences in whole-brain functional connectivity profiles discovered for the anterior and posterior hippocampal seeds were used to prescribe post-hoc ROIs, which were then used to perform ROI-to-ROI functional connectivity and graph-theoretic analyses. RESULTS: The PTSD group showed increased functional connectivity of the anterior hippocampus with affective brain regions (anterior/posterior insula, orbitofrontal cortex, temporal pole) and decreased functional connectivity of the anterior/posterior hippocampus with regions involved in processing bodily self-consciousness (supramarginal gyrus). Notably, decreased anterior hippocampus connectivity with the posterior cingulate cortex/precuneus was associated with increased PTSD symptom severity. The left anterior hippocampus also emerged as a central locus of abnormal functional connectivity, with graph-theoretic measures suggestive of a more central hub-like role for this region in those with PTSD compared to trauma-exposed controls. CONCLUSIONS: Our results highlight that the anterior hippocampus plays a critical role in the neurocircuitry underlying PTSD and underscore the importance of the differential roles of hippocampal sub-regions in serving as biomarkers of PTSD. Future studies should investigate whether the differential patterns of functional connectivity stemming from hippocampal sub-regions is observed in PTSD populations other than older war veterans.

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.

Associations between trauma and substance use among healthcare workers and public safety personnel during the SARS-CoV-2 (COVID-19) pandemic: the mediating roles of dissociation and emotion dysregulation.

BACKGROUND: Given the highly stressful environment surrounding the SARS-CoV-2 pandemic, healthcare workers (HCW) and public safety personnel (PSP) are at an elevated risk for adverse psychological outcomes, including posttraumatic stress disorder (PTSD) and alcohol/substance use problems. As such, the study aimed to identify associations between PTSD severity, related dissociation and emotion dysregulation symptoms, and alcohol/substance use problems among HCWs and PSP. METHODS: A subset of data (N = 498; HCWs = 299; PSP = 199) was extracted from a larger study examining psychological variables among Canadian HCWs and PSP during the pandemic. Structural equation modelling assessed associations between PTSD symptoms and alcohol/substance use-related problems with dissociation and emotion dysregulation as mediators. RESULTS: Among HCWs, dissociation fully mediated the relation between PTSD and alcohol-related problems (indirect effect ß = .133, p = .03) and emotion dysregulation partially mediated the relation between PTSD and substance-related problems (indirect effect ß = .151, p = .046). In PSP, emotion dysregulation fully mediated the relation between PTSD and alcohol-related problems (indirect effects ß = .184, p = .005). For substance-related problems among PSP, neither emotion dysregulation nor dissociation (ps >.05) had any effects. CONCLUSION: To our knowledge, this is the first study examining associations between PTSD severity and alcohol/substance use-related problems via mediating impacts of emotion dysregulation and dissociation among HCWs and PSP during the SARS-CoV-2 pandemic. These findings highlight dissociation and emotion dysregulation as important therapeutic targets for structured interventions aimed at reducing the burden of PTSD and/or SUD among Canadian HCWs or PSP suffering from the adverse mental health impacts of the SARS-CoV-2 pandemic.

Among healthcare workers, dissociation mediated relation between posttraumatic stress disorder (PTSD) severity and alcohol-related problems and emotion dysregulation mediated relation between PTSD severity and substance-related problems.Among public safety personnel, emotion dysregulation mediated relation between PTSD severity and alcohol-related problems. Neither dissociation nor emotion dysregulation mediated relation between PTSD severity and substance-related problems.Results underscore dissociation and emotion dysregulation as potential key therapeutic targets for intervention for healthcare workers and public safety personnel struggling with PTSD and comorbid alcohol/substance use-related problems.

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.

Increased top-down control of emotions during symptom provocation working memory tasks following a RCT of alpha-down neurofeedback in PTSD.

BACKGROUND: Posttraumatic stress disorder (PTSD) has been found to be associated with emotion under-modulation from the prefrontal cortex and a breakdown of the top-down control of cognition and emotion. Novel adjunct therapies such as neurofeedback (NFB) have been shown to normalize aberrant neural circuits that underlie PTSD psychopathology at rest. However, little evidence exists for NFB-linked neural improvements under emotionally relevant cognitive load. The current study sought to address this gap by examining the effects of alpha-down NFB in the context of an emotional n-back task. METHODS: We conducted a 20-week double-blind randomized, sham-controlled trial of alpha-down NFB and collected neuroimaging data before and after the NFB protocol. Participants performed an emotional 1-back and 2-back working memory task, with interleaved trauma-neutral and trauma-relevant cues in the fMRI scanner. Data from 35 participants with a primary diagnosis of PTSD were analyzed in this study (n = 18 in the experimental group undergoing alpha-down NFB, n = 17 in the sham-control group). RESULTS: Firstly, within-group analyses showed clinically significant reductions in PTSD symptom severity scores at the post-intervention timepoint and 3-month follow-up for the experimental group, and not for the sham-control group. The neuroimaging analyses revealed that alpha-down NFB enhanced engagement of top-down cognitive and emotional control centers, such as the dorsolateral prefrontal cortex (dlPFC), and improved integration of the anterior and posterior parts of the default mode network (DMN). Finally, our results also indicate that increased alpha-down NFB performance correlated with increased activity in brain regions involved in top-down control and bodily consciousness/embodied processing of self (TPJ and posterior insula). CONCLUSION: This is the first study to provide mechanistic insights into how NFB may normalize dysfunctional brain activity and connectivity in PTSD under cognitive load with simultaneous symptom provocation, adding to a growing body of evidence supporting the therapeutic neuromodulatory effects of NFB. This preliminary study highlights the benefits of alpha-down NFB training as an adjunctive therapy for PTSD and warrants further investigation into its therapeutic effects on cognitive and emotion control in those with PTSD.

A brief transdiagnostic psychological intervention for Afghan asylum seekers and refugees in Austria: a randomized controlled trial.

Background: Afghan refugees often face hardship and traumatic experiences before, during, and after migration and frequently suffer from mental health burdens. Evidence based psychological treatments for refugees mostly focus on symptoms of posttraumatic stress disorder (PTSD), however, refugees often suffer from a variety of general health problems as well as depression and anxiety. We thus aimed to evaluate the effectiveness of a transdiagnostic psychological intervention. Objective: To investigate the effectiveness of an adapted version of Problem Management Plus (aPM+) delivered by mental health professionals to adult Afghan refugees and asylum seekers. Methods: We randomly allocated 88 Afghan refugees either to aPM+ in addition to treatment as usual (aPM+/TAU) or TAU alone. APM+ comprises of six weekly 90-minute individual sessions including strategies of stress management, problem solving, behavioural activation, strengthening social support and either anger regulation or increasing self-efficacy. The primary outcome was general health (GHQ-28) post intervention. Secondary outcome measures included distress by PMLD, Complex PTSD symptoms, quality of life, self-identified problems, and integration. Results: Attrition was high: 42% of the randomized participants did not participate in the post-treatment assessment. A repeated measures per-protocol (completers only) ANCOVA evidenced a significant group × timepoint interaction for GHQ total scores [F(1, 47) = 14.80, p < .001, partial η2 = 0.24]. Post-hoc analyses showed significantly lower symptoms in the aPM+/TAU arm (n = 26) as compared to the TAU arm (n = 25) for the GHQ total scores (dz = 1.04). Most secondary outcomes significantly improved in the aPM+/TAU arm, but not in the TAU arm. Conclusion: APM+ was effective in reducing general health problems in Afghan refugees and might be considered as a first-line intervention. High drop-out rate limit the interpretations of our results, where future investigations should focus on possibilities to reduce these rates.Trial registration: Uniform Trial Number identifier: U1111-1226-3285. HIGHLIGHTS: Refugees' mental health can be strengthened with a brief psychological intervention that also focuses on skills in the context of post-migration stressors.High drop-out rates are a major challenge for future research and delivery of psychological interventions as part of health care systems to refugees and asylum seekers.

Mental health professionals' perspective on a brief transdiagnostic psychological intervention for Afghan asylum seekers and refugees.

Background: While many elaborated treatment protocols focus on post-traumatic stress symptoms, a large number of refugees suffer from a range of mental health problems. Thus, brief and transdiagnostic psychological interventions may be helpful first interventions for help-seeking refugees and asylum seekers in a stepped-care approach. Critically, there is limited research on how transdiagnostic interventions are received in general practice in non-specialized mental healthcare settings in high-income countries, where often only mental health professionals (MHPs) are legally allowed to treat people with mental disorders. MHPs may thus deliver such interventions, but their perspective towards them has not yet been investigated. Objective: We aimed to investigate MHPs' perception of the usability of adapted Problem Management Plus (aPM+), a brief transdiagnostic psychological intervention for refugees, which we adapted to address distress caused by post-migration living difficulties (PMLDs). Method: Employing an e-learning tool, we introduced the aPM+ intervention to 59 MHPs and assessed their perspective towards the intervention. We then used an inductive approach to analyse their perspective towards the intervention with open-ended questions. Results: Altogether, 59 MHPs enrolled in the webinar and 29 provided feedback on the intervention. MHPs had a positive view on the intervention but emphasized the importance of situation-specific adaptations to the structure of the manual. The most favoured specific strategies were 'managing stress/slow-breathing', the 'tree of capabilities', and the 'riding the anger' exercise. The last two were additionally developed to reduce distress caused by PMLDs by either enhancing self-efficacy or reducing anger regulation difficulties. Conclusions: An adaptation to aPM+ regarding more flexibility of the manual may enhance the likelihood of MHPs implementing the intervention in their daily practice. Strategies addressing coping with PMLDs could be particularly helpful.Trial registration: German Clinical Trials Register identifier: DRKS00016538. HIGHLIGHTS: Mental health professionals had a positive view on a brief transdiagnostic psychological intervention for refugees but emphasized the importance of situation-specific adaptations to the structure of the manual.Low -intensity interventions may be useful not only in low- and middle-income countries but also in high-income countries as part of a stepped-care approach, even if distributed by MHPs instead of trained laypersons.

Antecedentes: Mientras que muchos protocolos de tratamiento elaborados se enfocan en los síntomas de estrés postraumático, un gran número de refugiados sufren de un rango de problemas de salud mental. Por lo tanto, las intervenciones psicológicas breves y transdiagnósticas pueden ser primeras intervenciones útiles para refugiados en búsqueda de ayuda y solicitantes de asilo en un enfoque de cuidado escalonado. Críticamente, hay limitada investigación sobre el cómo son recibidas las intervenciones transdiagnósticas en la práctica general en entornos de atención de salud no especializados en países de altos ingresos, donde en general sólo se permite legalmente que profesionales de salud mental (PSM en su sigla en inglés) traten a personas con trastornos mentales. Los PSM pueden por tanto entregar tales intervenciones, pero su perspectiva hacia ellas no ha sido aún investigada.Objetivo: Buscamos investigar la percepción de los PSM de la utilidad de Manejo de Problemas Plus adaptada (aPM+, por su sigla en inglés), una intervención psicológica breve transdiagnóstica para refugiados, que adaptamos para abordar el sufrimiento por dificultades vitales post-migración (PMLD por su sigla en inglés).Método: Utilizando una herramienta de e-learning, presentamos la intervención aPM+ a 59 PSM y evaluamos su perspectiva hacia la intervención. Usamos entonces un abordaje inductivo para analizar la perspectiva hacia la intervención con preguntas abiertas.Resultados: En total, 59 PSM se inscribieron en el webinar y 29 proporcionaron retroalimentación sobre la intervención. Los PSM tuvieron una visión positiva de la intervención pero enfatizaron la importancia de las adaptaciones a la estructura del manual específicas a la situación. Las estrategias específicas más favorecidas fueron 'manejando el estrés/respiración pausada' y el 'árbol de capacidades' y el ejercicio 'montando la ira'. Los dos últimos fueron desarrollados adicionalmente para reducir el sufrimiento causado por PLMD a través de la potenciación de la autoeficacia o la reducción de las dificultades de la regulación de la ira.Conclusiones: Una adaptación a aPM+ en relación a una mayor flexibilidad del manual podría aumentar la probabilidad de que los PSM implementen la intervención en su práctica diaria. Las estrategias que aborden el afrontamiento de PMLD podrían ser particularmente útiles.

A systematic review of the neural correlates of sexual minority stress: towards an intersectional minority mosaic framework with implications for a future research agenda.

BACKGROUND: Systemic oppression, particularly towards sexual minorities, continues to be deeply rooted in the bedrock of many societies globally. Experiences with minority stressors (e.g. discrimination, hate-crimes, internalized homonegativity, rejection sensitivity, and microaggressions or everyday indignities) have been consistently linked to adverse mental health outcomes. Elucidating the neural adaptations associated with minority stress exposure will be critical for furthering our understanding of how sexual minorities become disproportionately affected by mental health burdens.Following PRISMA-guidelines, we systematically reviewed published neuroimaging studies that compared neural dynamics among sexual minority and heterosexual populations, aggregating information pertaining to any measurement of minority stress and relevant clinical phenomena. RESULTS: Only 1 of 13 studies eligible for inclusion examined minority stress directly, where all other studies focused on investigating the neurobiological basis of sexual orientation. In our narrative synthesis, we highlight important themes that suggest minority stress exposure may be associated with decreased activation and functional connectivity within the default-mode network (related to the sense-of-self and social cognition), and summarize preliminary evidence related to aberrant neural dynamics within the salience network (involved in threat detection and fear processing) and the central executive network (involved in executive functioning and emotion regulation). Importantly, this parallels neural adaptations commonly observed among individuals with posttraumatic stress disorder (PTSD) in the aftermath of trauma and supports the inclusion of insidious forms of trauma related to minority stress within models of PTSD. CONCLUSIONS: Taken together, minority stress may have several shared neuropsychological pathways with PTSD and stress-related disorders. Here, we outline a detailed research agenda that provides an overview of literature linking sexual minority stress to PTSD and insidious trauma, moral affect (including shame and guilt), and mental health risk/resiliency, in addition to racial, ethnic, and gender related minority stress. Finally, we propose a novel minority mosaic framework designed to inform future directions of minority stress neuroimaging research from an intersectional lens.

Antecedentes: La opresión sistémica, en particular hacia las minorías sexuales, sigue estando profundamente arraigada en los cimientos de muchas sociedades a nivel mundial. Las experiencias con los factores de estrés de las minorías (por ejemplo, la discriminación, los delitos de odio, la homonegatividad interiorizada, la sensibilidad al rechazo y las microagresiones o humillaciones cotidianas) se han relacionado sistemáticamente con resultados adversos para la salud mental. La elucidación de las adaptaciones neuronales asociadas con la exposición al estrés de las minorías será fundamental para avanzar en nuestra comprensión de cómo las minorías sexuales se ven afectadas de manera desproporcionada por las cargas de salud mental.Métodos: Siguiendo las directrices PRISMA, revisamos sistemáticamente los estudios de neuroimagen publicados que comparaban la dinámica neural entre las poblaciones de minorías sexuales y heterosexuales, agregando la información relativa a cualquier medición del estrés de minorías y los fenómenos clínicos relevantes.Resultados: Sólo 1 de los 13 estudios elegibles para su inclusión examinó directamente el estrés de las minorías, mientras que todos los demás estudios se centraron en investigar las bases neurobiológicas de la orientación sexual. En nuestra síntesis narrativa, destacamos temas importantes que sugieren que la exposición al estrés de las minorías puede estar asociada con la disminución de la activación y la conectividad funcional dentro de la red del modo por defecto (relacionada con el sentido del yo y la cognición social), y resumimos la evidencia preliminar relacionada con la dinámica neuronal aberrante dentro de la red de saliencia (involucrada en la detección de amenazas y el procesamiento del miedo) y la red ejecutiva central (involucrada en el funcionamiento ejecutivo y la regulación de las emociones). Es importante destacar que esto es paralelo a las adaptaciones neuronales comúnmente observadas entre los individuos con trastorno de estrés postraumático (TEPT) después del trauma y apoya la inclusión de formas insidiosas de trauma relacionadas con el estrés de las minorías dentro de los modelos de TEPT.Conclusiones: En conjunto, el estrés de las minorías puede tener varias vías neuropsicológicas compartidas con el TEPT y los trastornos relacionados con el estrés. Aquí, esbozamos una agenda de investigación detallada que proporciona una visión general de la literatura que vincula el estrés de las minorías sexuales con el TEPT y el trauma insidioso, el afecto moral (incluyendo la vergüenza y la culpa), y el riesgo/resiliencia de la salud mental, además del estrés de las minorías relacionadas con la raza, la etnia y el género. Por último, proponemos un marco de mosaico de minorías novedoso diseñado para informar sobre las futuras direcciones de la investigación de neuroimagen del estrés de las minorías desde una perspectiva interseccional.

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.

Progressive modulation of resting-state brain activity during neurofeedback of positive-social emotion regulation networks.

Neurofeedback allows for the self-regulation of brain circuits implicated in specific maladaptive behaviors, leading to persistent changes in brain activity and connectivity. Positive-social emotion regulation neurofeedback enhances emotion regulation capabilities, which is critical for reducing the severity of various psychiatric disorders. Training dorsomedial prefrontal cortex (dmPFC) to exert a top-down influence on bilateral amygdala during positive-social emotion regulation progressively (linearly) modulates connectivity within the trained network and induces positive mood. However, the processes during rest that interleave the neurofeedback training remain poorly understood. We hypothesized that short resting periods at the end of training sessions of positive-social emotion regulation neurofeedback would show alterations within emotion regulation and neurofeedback learning networks. We used complementary model-based and data-driven approaches to assess how resting-state connectivity relates to neurofeedback changes at the end of training sessions. In the experimental group, we found lower progressive dmPFC self-inhibition and an increase of connectivity in networks engaged in emotion regulation, neurofeedback learning, visuospatial processing, and memory. Our findings highlight a large-scale synergy between neurofeedback and resting-state brain activity and connectivity changes within the target network and beyond. This work contributes to our understanding of concomitant learning mechanisms post training and facilitates development of efficient neurofeedback training.

Securing Your Relationship: Quality of Intimate Relationships During the COVID-19 Pandemic Can Be Predicted by Attachment Style.

The COVID-19 pandemic along with the restrictions that were introduced within Europe starting in spring 2020 allows for the identification of predictors for relationship quality during unstable and stressful times. The present study began as strict measures were enforced in response to the rising spread of the COVID-19 virus within Austria, Poland, Spain and Czech Republic. Here, we investigated quality of romantic relationships among 313 participants as movement restrictions were implemented and subsequently phased out cross-nationally. Participants completed self-report questionnaires over a period of 7 weeks, where we predicted relationship quality and change in relationship quality using machine learning models that included a variety of potential predictors related to psychological, demographic and environmental variables. On average, our machine learning models predicted 29% (linear models) and 22% (non-linear models) of the variance with regard to relationship quality. Here, the most important predictors consisted of attachment style (anxious attachment being more influential than avoidant), age, and number of conflicts within the relationship. Interestingly, environmental factors such as the local severity of the pandemic did not exert a measurable influence with respect to predicting relationship quality. As opposed to overall relationship quality, the change in relationship quality during lockdown restrictions could not be predicted accurately by our machine learning models when utilizing our selected features. In conclusion, we demonstrate cross-culturally that attachment security is a major predictor of relationship quality during COVID-19 lockdown restrictions, whereas fear, pathogenic threat, sexual behavior, and the severity of governmental regulations did not significantly influence the accuracy of prediction.

Predictors of real-time fMRI neurofeedback performance and improvement - A machine learning mega-analysis.

Real-time fMRI neurofeedback is an increasingly popular neuroimaging technique that allows an individual to gain control over his/her own brain signals, which can lead to improvements in behavior in healthy participants as well as to improvements of clinical symptoms in patient populations. However, a considerably large ratio of participants undergoing neurofeedback training do not learn to control their own brain signals and, consequently, do not benefit from neurofeedback interventions, which limits clinical efficacy of neurofeedback interventions. As neurofeedback success varies between studies and participants, it is important to identify factors that might influence neurofeedback success. Here, for the first time, we employed a big data machine learning approach to investigate the influence of 20 different design-specific (e.g. activity vs. connectivity feedback), region of interest-specific (e.g. cortical vs. subcortical) and subject-specific factors (e.g. age) on neurofeedback performance and improvement in 608 participants from 28 independent experiments. With a classification accuracy of 60% (considerably different from chance level), we identified two factors that significantly influenced neurofeedback performance: Both the inclusion of a pre-training no-feedback run before neurofeedback training and neurofeedback training of patients as compared to healthy participants were associated with better neurofeedback performance. The positive effect of pre-training no-feedback runs on neurofeedback performance might be due to the familiarization of participants with the neurofeedback setup and the mental imagery task before neurofeedback training runs. Better performance of patients as compared to healthy participants might be driven by higher motivation of patients, higher ranges for the regulation of dysfunctional brain signals, or a more extensive piloting of clinical experimental paradigms. Due to the large heterogeneity of our dataset, these findings likely generalize across neurofeedback studies, thus providing guidance for designing more efficient neurofeedback studies specifically for improving clinical neurofeedback-based interventions. To facilitate the development of data-driven recommendations for specific design details and subpopulations the field would benefit from stronger engagement in open science research practices and data sharing.

Predicting fear and perceived health during the COVID-19 pandemic using machine learning: A cross-national longitudinal study.

During medical pandemics, protective behaviors need to be motivated by effective communication, where finding predictors of fear and perceived health is of critical importance. The varying trajectories of the COVID-19 pandemic in different countries afford the opportunity to assess the unique influence of 'macro-level' environmental factors and 'micro-level' psychological variables on both fear and perceived health. Here, we investigate predictors of fear and perceived health using machine learning as lockdown restrictions in response to the COVID-19 pandemic were introduced in Austria, Spain, Poland and Czech Republic. Over a seven-week period, 533 participants completed weekly self-report surveys which measured the target variables subjective fear of the virus and perceived health, in addition to potential predictive variables related to psychological factors, social factors, perceived vulnerability to disease (PVD), and economic circumstances. Viral spread, mortality and governmental responses were further included in the analysis as potential environmental predictors. Results revealed that our models could accurately predict fear of the virus (accounting for approximately 23% of the variance) using predictive factors such as worrying about shortages in food supplies and perceived vulnerability to disease (PVD), where interestingly, environmental factors such as spread of the virus and governmental restrictions did not contribute to this prediction. Furthermore, our results revealed that perceived health could be predicted using PVD, physical exercise, attachment anxiety and age as input features, albeit with smaller effect sizes. Taken together, our results emphasize the importance of 'micro-level' psychological factors, as opposed to 'macro-level' environmental factors, when predicting fear and perceived health, and offer a starting point for more extensive research on the influences of pathogen threat and governmental restrictions on the psychology of fear and health.

Shame on the brain: Neural correlates of moral injury event recall in posttraumatic stress disorder.

BACKGROUND: Moral injury (MI) is consistently associated with adverse mental health outcomes, including the development of posttraumatic stress disorder (PTSD) and suicidality. METHODS: We investigated neural activation patterns associated with MI event recall using functional magnetic resonance imaging in participants with military and public safety-related PTSD, relative to civilian MI-exposed controls. RESULTS: MI recall in the PTSD as compared to control group was associated with increased neural activation among salience network nodes involved in viscerosensory processing and hyperarousal (right posterior insula, dorsal anterior cingulate cortex; dACC), regions involved in defensive responding (left postcentral gyrus), and areas responsible for top-down cognitive control of emotions (left dorsolateral prefrontal cortex; dlPFC). Within the PTSD group, measures of state and trait shame correlated negatively with activity among default mode network regions associated with self-related processing and moral cognition (dorsomedial prefrontal cortex; dmPFC) and salience network regions associated with viscerosensory processing (left posterior insula), respectively. CONCLUSIONS: These findings suggest that MI event processing is altered in military and public safety-related PTSD, relative to MI-exposed controls. Here, it appears probable that as individuals with PTSD recall their MI event, they experience a surge of blame-related processing of bodily sensations within salience network regions, including the right posterior insula and the dACC, which in turn, prompt regulatory strategies at the level of the left dlPFC aimed at increasing cognitive control and inhibiting emotional affect. These results are consistent with previous findings showing enhanced sensory processing and altered top-down control in PTSD samples during autobiographical memory recall.

The hijacked self: Disrupted functional connectivity between the periaqueductal gray and the default mode network in posttraumatic stress disorder using dynamic causal modeling.

Self-related processes define assorted self-relevant or social-cognitive functions that allow us to gather insight and to draw inferences related to our own mental conditions. Self-related processes are mediated by the default mode network (DMN), which, critically, shows altered functionality in individuals with posttraumatic stress disorder (PTSD). In PTSD, the midbrain periaqueductal gray (PAG) demonstrates stronger functional connectivity with the DMN [i.e., precuneus (PCN), medial prefrontal cortex (mPFC)] as compared to healthy individuals during subliminal, trauma-related stimulus processing. Here, we analyzed the directed functional connectivity between the PAG and the PCN, as well as between the PAG and the mPFC to more explicitly characterize the functional connectivity we have observed previously on the corresponding sample and paradigm. We evaluated three models varying with regard to context-dependent modulatory directions (i.e., bi-directional, bottom-up, top-down) among individuals with PTSD (n = 26) and healthy participants (n = 20), where Bayesian model selection was used to identify the most optimal model for each group. We then compared the effective connectivity strength for each parameter across the models and between our groups using Bayesian model averaging. Bi-directional models were found to be favoured across both groups. In PTSD, we revealed the PAG to show stronger excitatory effective connectivity to the PCN, as well as to the mPFC as compared to controls. In PTSD, we further demonstrated that PAG-mediated effective connectivity to the PCN, as well as to the mPFC were modulated more strongly during subliminal, trauma-related stimulus conditions as compared to controls. Clinical disturbances towards self-related processes are reported widely by participants with PTSD during trauma-related stimulus processing, where altered functional connectivity directed by the PAG to the DMN may elucidate experiential links between self- and trauma-related processing in traumatized individuals.

Classifying heterogeneous presentations of PTSD via the default mode, central executive, and salience networks with machine learning.

Intrinsic connectivity networks (ICNs), including the default mode network (DMN), the central executive network (CEN), and the salience network (SN) have been shown to be aberrant in patients with posttraumatic stress disorder (PTSD). The purpose of the current study was to a) compare ICN functional connectivity between PTSD, dissociative subtype PTSD (PTSD+DS) and healthy individuals; and b) to examine the use of multivariate machine learning algorithms in classifying PTSD, PTSD+DS, and healthy individuals based on ICN functional activation. Our neuroimaging dataset consisted of resting-state fMRI scans from 186 participants [PTSD (n = 81); PTSD + DS (n = 49); and healthy controls (n = 56)]. We performed group-level independent component analyses to evaluate functional connectivity differences within each ICN. Multiclass Gaussian Process Classification algorithms within PRoNTo software were then used to predict the diagnosis of PTSD, PTSD+DS, and healthy individuals based on ICN functional activation. When comparing the functional connectivity of ICNs between PTSD, PTSD+DS and healthy controls, we found differential patterns of connectivity to brain regions involved in emotion regulation, in addition to limbic structures and areas involved in self-referential processing, interoception, bodily self-consciousness, and depersonalization/derealization. Machine learning algorithms were able to predict with high accuracy the classification of PTSD, PTSD+DS, and healthy individuals based on ICN functional activation. Our results suggest that alterations within intrinsic connectivity networks may underlie unique psychopathology and symptom presentation among PTSD subtypes. Furthermore, the current findings substantiate the use of machine learning algorithms for classifying subtypes of PTSD illness based on ICNs.