The emotional states and associated behavioral responses (flexible-adaptive behaviors vs. inflexible-maladaptive behaviors) of cancer patients during the SARS-CoV-2 outbreak: A multi-center cross-sectional study in Italy.

OBJECTIVE: Distress during SARS-CoV-2 outbreak affected also cancer patients' well-being. Aim of this study was to investigate patient' reactions and behavior (flexible-adaptive vs. inflexible-maladaptive) during the SARS-CoV-2 outbreak. METHODS: A cross-sectional survey was designed with a self-report questionnaire, "the ImpACT questionnaire," developed for the study. Regression analysis was performed on data. RESULTS: Four hundred and forty five cancer patients from 17 Italian regions participated in the study. 79.8% of participants were female (mean age of 58 years). 92.6% of participants reported feeling vulnerable to COVID-19 contagion; 75.6% reported helpless, 62.7% sad, 60.4% anxious, and 52.0% anger. Avoidance of thinking about coronavirus is the principal maladaptive behavior that emerged. Participants who reported feeling anxious were more likely to have fear of staff being infected with COVID-19 (OR = 3.01; 95% CI = 1.49-6.30) and to have disrupted sleep due to worry (OR = 2.42; 95% CI = 1.23-4.83). Younger participants reported more anxiety (OR = 0.97; 95% CI = 0.94-1.00); men reported feeling calm more than women (OR = 2.60; 95% CI = 1.27-5.43). CONCLUSIONS: Majority of cancer patients reported serious concerns regarding SARS-CoV-2 infection; reliable information and psychological support must be offers to respond to these needs.

Graded Exposure Therapy for Fear Avoidance Behaviour After Concussion (GET FAB): protocol for a multisite Canadian randomised controlled trial.

INTRODUCTION: Persistent symptoms after mild traumatic brain injury (mTBI) negatively affect daily functioning and quality of life. Fear avoidance behaviour, a coping style in which people avoid or escape from activities or situations that they expect will exacerbate their symptoms, maybe a particularly potent and modifiable risk factor for chronic disability after mTBI. This study will evaluate the efficacy of graded exposure therapy (GET) for reducing persistent symptoms following mTBI, with two primary aims: (1) To determine whether GET is more effective than usual care; (2) to identify for whom GET is the most effective treatment option, by evaluating whether baseline fear avoidance moderates differences between GET and an active comparator (prescribed aerobic exercise). Our findings will guide evidence-based care after mTBI and enable better matching of mTBI patients to treatments. METHODS AND ANALYSIS: We will conduct a multisite randomised controlled trial with three arms. Participants (n=220) will be recruited from concussion clinics and emergency departments in three Canadian provinces and randomly assigned (1:2:2 ratio) to receive enhanced usual care, GET or prescribed aerobic exercise. The outcome assessment will occur remotely 14-18 weeks following baseline assessment, after completing the 12-week treatment phase. The primary outcome will be symptom severity (Rivermead Post-concussion Symptoms Questionnaire). ETHICS AND DISSEMINATION: Informed consent will be obtained from all participants. All study procedures were approved by the local research ethics boards (University of British Columbia Clinical Research Ethics Board, University of Calgary Conjoint Health Research Ethics Board, University Health Network Research Ethics Board-Panel D). Operational approvals were obtained for Vancouver Coastal Health Research Institute and Provincial Health Services Authority. If GET proves effective, we will disseminate the GET treatment manual and present instructional workshops for clinicians. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov #NCT05365776.

Zona incerta mediates early life isoflurane-induced fear memory deficits.

The potential long-term effects of anesthesia on cognitive development, especially in neonates and infants, have raised concerns. However, our understanding of its underlying mechanisms and effective treatments is still limited. In this study, we found that early exposure to isoflurane (ISO) impaired fear memory retrieval, which was reversed by dexmedetomidine (DEX) pre-treatment. Measurement of c-fos expression revealed that ISO exposure significantly increased neuronal activation in the zona incerta (ZI). Fiber photometry recording showed that ZI neurons from ISO mice displayed enhanced calcium activity during retrieval of fear memory compared to the control group, while DEX treatment reduced this enhanced calcium activity. Chemogenetic inhibition of ZI neurons effectively rescued the impairments caused by ISO exposure. These findings suggest that the ZI may play a pivotal role in mediating the cognitive effects of anesthetics, offering a potential therapeutic target for preventing anesthesia-related cognitive impairments.

Being able to think when caught in the maelstrom - how adolescents used mindfulness when facing exams.

PURPOSE: Research indicates that exam anxiety may decline with mindfulness-based interventions but there is a lack of research on adolescents' accounts of the processes involved. We explored high-school students' descriptions of how they perceived and applied mindfulness in managing anxiety-inducing thoughts related to academic performance following an 8-week Mindfulness-Based Stress Reduction (MBSR) course. METHOD: Post-course individual semi-structured interviews with 22 high school students (2 males, mean age 17.8 years) were transcribed verbatim and analysed using reflexive thematic analysis. RESULTS: The analyses identified six themes: (1) Noticing and attending to the attention-binding "maelstrom" of anxious thoughts and feelings (2) Attending to the breath to cope with the maelstrom, (3) "removing" and "getting rid of" anxious thoughts (4) Being able to "think" (5) awareness of more helpful thoughts, and (6) Agency and control. The findings are discussed in light of the Buddhist notion of "unwholesome thoughts" and the distinction between thought suppression and the use of breathing as a benign distraction. We propose that mindfulness encompasses both a receptive, nonjudgmental awareness and an active, intentional redirection of attention. CONCLUSION: Mindfulness training aided participants by enhancing their capacity to disengage from fear-engaging thoughts, thereby maintaining them within their window of tolerance and facilitating cognitive processing.

Sex differences in neural projections of fear memory processing in mice and humans.

It remains unexplored in the field of fear memory whether functional neuronal connectivity between two brain areas is necessary for one sex but not the other. Here, we show that chemogenetic silencing of centromedial (CeM)-Tac2 fibers in the lateral posterior BNST (BNSTpl) decreased fear memory consolidation in male mice but not females. Optogenetic excitation of CeM-Tac2 fibers in the BNSTpl exhibited enhanced inhibitory postsynaptic currents in males compared to females. In vivo calcium imaging analysis revealed a sex-dimorphic fear memory engram in the BNSTpl. Furthermore, in humans, the single-nucleotide polymorphism (SNP) in the Tac2 receptor (rs2765) (TAC3R) decreased CeM-BNST connectivity in a fear task, impaired fear memory consolidation, and increased the expression of the TAC3R mRNA in AA-carrier men but not in women. These sex differences in critical neuronal circuits underlying fear memory formation may be relevant to human neuropsychiatric disorders with fear memory alterations such as posttraumatic stress disorder.

Exploring the fear of clinical errors: associations with socio-demographic, professional, burnout, and mental health factors in healthcare workers - A nationwide cross-sectional study.

Background: The fear of clinical errors among healthcare workers (HCW) is an understudied aspect of patient safety. This study aims to describe this phenomenon among HCW and identify associated socio-demographic, professional, burnout and mental health factors. Methods: We conducted a nationwide, online, cross-sectional study targeting HCW in France from May to June 2021. Recruitment was through social networks, professional networks, and email invitations. To assess the fear of making clinical errors, HCW were asked: "During your daily activities, how often are you afraid of making a professional error that could jeopardize patient safety?" Responses were collected on a 7-point Likert-type scale. HCW were categorized into "High Fear" for those who reported experiencing fear frequently ("once a week," "a few times a week," or "every day"), vs. "Low Fear" for less often. We used multivariate logistic regression to analyze associations between fear of clinical errors and various factors, including sociodemographic, professional, burnout, and mental health. Structural equation modeling was used to explore how this fear fits into a comprehensive theoretical framework. Results: We recruited a total of 10,325 HCW, of whom 25.9% reported "High Fear" (95% CI: 25.0-26.7%). Multivariate analysis revealed higher odds of "High Fear" among males, younger individuals, and those with less professional experience. High fear was more notable among physicians and nurses, and those working in critical care and surgery, on night shifts or with irregular schedules. Significant associations were found between "High Fear" and burnout, low professional support, major depressive disorder, and sleep disorders. Conclusions: Fear of clinical errors is associated with factors that also influence patient safety, highlighting the importance of this experience. Incorporating this dimension into patient safety culture assessment could provide valuable insights and could inform ways to proactively enhance patient safety.

Testing an Imagery Rescripting Exercise Targeting Fear of Self.

A feared possible self refers to the unwanted characteristics that a person may possess or develop. We tested an experimental paradigm to target fear of possible self using imagery rescripting. A student sample (n = 91), with moderate obsessive-compulsive disorder symptoms, engaged in written and audio-guided exercises to evoke episodic future mental imagery that represented their feared possible self. Participants were then randomized between imagery rescripting or neutral imagery control tasks. The results revealed no difference between conditions in fear of self or general obsessional beliefs following the manipulation. State anxiety and the urge to neutralize the imagery reduced more in the control condition than in the rescripting condition. These findings suggest that the current paradigm is emotionally engaging but not effective at addressing fear of self as measured. Methodological improvements such as removing a written component of the rescripting task and idiosyncratic measuring of fear of self are proposed.

Dominant activities of fear engram cells in the dorsal dentate gyrus underlie fear generalization in mice.

Over-generalized fear is a maladaptive response to harmless stimuli or situations characteristic of posttraumatic stress disorder (PTSD) and other anxiety disorders. The dorsal dentate gyrus (dDG) contains engram cells that play a crucial role in accurate memory retrieval. However, the coordination mechanism of neuronal subpopulations within the dDG network during fear generalization is not well understood. Here, with the Tet-off system combined with immunostaining and two-photon calcium imaging, we report that dDG fear engram cells labeled in the conditioned context constitutes a significantly higher proportion of dDG neurons activated in a similar context where mice show generalized fear. The activation of these dDG fear engram cells encoding the conditioned context is both sufficient and necessary for inducing fear generalization in the similar context. Activities of mossy cells in the ventral dentate gyrus (vMCs) are significantly suppressed in mice showing fear generalization in a similar context, and activating the vMCs-dDG pathway suppresses generalized but not conditioned fear. Finally, modifying fear memory engrams in the dDG with "safety" signals effectively rescues fear generalization. These findings reveal that the competitive advantage of dDG engram cells underlies fear generalization, which can be rescued by activating the vMCs-dDG pathway or modifying fear memory engrams, and provide novel insights into the dDG network as the neuronal basis of fear generalization.

Interaction between the prefrontal and visual cortices supports subjective fear.

It has been reported that threatening and non-threatening visual stimuli can be distinguished based on the multi-voxel patterns of haemodynamic activity in the human ventral visual stream. Do these findings mean that there may be evolutionarily hardwired mechanisms within early perception, for the fast and automatic detection of threat, and maybe even for the generation of the subjective experience of fear? In this human neuroimaging study, we presented participants ('fear' group: N = 30; 'no fear' group: N = 30) with 2700 images of animals that could trigger subjective fear or not as a function of the individual's idiosyncratic 'fear profiles' (i.e. fear ratings of animals reported by a given participant). We provide evidence that the ventral visual stream may represent affectively neutral visual features that are statistically associated with fear ratings of participants, without representing the subjective experience of fear itself. More specifically, we show that patterns of haemodynamic activity predictive of a specific 'fear profile' can be observed in the ventral visual stream whether a participant reports being afraid of the stimuli or not. Further, we found that the multivariate information synchronization between ventral visual areas and prefrontal regions distinguished participants who reported being subjectively afraid of the stimuli from those who did not. Together, these findings support the view that the subjective experience of fear may depend on the relevant visual information triggering implicit metacognitive mechanisms in the prefrontal cortex. This article is part of the theme issue 'Sensing and feeling: an integrative approach to sensory processing and emotional experience'.

Predicting psychological distress in advanced ovarian cancer patients during the COVID-19 pandemic.

PURPOSE: This longitudinal study investigated distress rates in patients with advanced ovarian cancer during the COVID-19 pandemic and examined whether time, illness representations, and coping strategies predicted distress levels. METHODS: UK patients with stage 3 or 4 ovarian cancer were recruited between September 2020 and March 2021. Data were collected at baseline (T0), 2 months (T1), and 4 months (T2) post-enrolment. Validated questionnaires assessed distress (anxiety, depression, PTSD, fear of progression) and predictors (coping strategies and illness perceptions), analysed via multilevel modelling. RESULTS: Seventy-two participants returned a questionnaire at T0, decreasing to 49 by T2. High distress was observed, with over 50% of participants experiencing anxiety and depression consistently. Nearly 60% reported clinical levels of fear of progression at some point. PTSD rates resembled the general population. Although distress levels remained stable over time, some individual variability was observed. Time had minimal effect on distress. Coping strategies and illness perceptions remained stable. Threatening illness perceptions consistently predicted distress, while specific coping strategies such as active coping, acceptance, self-blame, and humour predicted various aspects of distress. Together, these factors explained up to half of the distress variance. CONCLUSION: The findings have implications for routine screening for distress and the inclusion of psychological treatment pathways in advanced ovarian cancer care. Addressing illness representations is crucial, with attention to informational support. Future research should explore the long-term effects of heightened distress and the effectiveness of interventions targeting illness perceptions. This study informs current clinical practice and future pandemic preparedness in cancer care.

Neuroethology: Fear outside the box.

Behavioral neuroscience has successfully and in great detail deconstructed circuit mechanisms underlying fear behaviors using reductionist approaches. Recent research in more naturalistic settings now reveals additional higher-level organization, where hypothalamic circuits multiplex threat detection and fear memory updating to safely navigate complex environments.

Neck Kinematics in Patients With Chronic Mechanical Neck Pain: An Observational Study to Explore the Integration of Multiple Influencing Factors Through a Bayesian Model-Based Approach.

The aim of this observational, cross-sectional study is to evaluate potential differences in kinematics, specifically range of motion (ROM) and velocity, during planar cervical movements between patients with non-traumatic chronic neck pain and disability and asymptomatic controls, while accounting for potential influencing variables of age, sex and fear of movement. The influence of pain intensity, neck disability, age, sex or fear of motion on kinematics was analyzed through robust multivariate Bayesian regression models fitted using the brms library in R. Forty-three patients with neck pain (aged 36.70 ± 13.75 years; 10 men and 33 women) and 42 asymptomatic participants (aged 32.74 ± 13.24 years; 25 men and 17 women) completed the study protocol. The presence of neck pain/disability was associated with lower ROM and peak velocity during all planar movements when considering the influence of age, sex or fear of motion, with standardized regression coefficients that had a small effect size (ranged from 0.11 to 0.28) and estimated differences of less than 2.21° in ROM and 25.61°/s in peak velocity. Although patients with chronic mechanical neck pain showed reduced ROM and peak velocity, the small effect sizes and the low estimated differences between groups question the relevance and clinical usefulness of kinematic analysis of planar movements in samples of patients similar to those included in our study. It is probable that there are differences between the groups, but it is insufficient to rely solely on kinematic variables for patient discrimination. This limitation likely arises from the substantial variability in patient kinematics.

Natural clues to danger: attachment behavior in threatening situations.

A fundamental principle of attachment theory is that threatening situations give rise to individual differences in the extent to which people seek proximity to close others. The current research examines the way in which attachment styles predict individual differences in attachment-relevant behavior during threatening events. We tested alternative theoretical perspectives concerning the association between adult attachment (specifically, attachment avoidance) and attachment behavior in the presence of natural clues to danger by observing couples (N = 204) when they were watching horror vs. control film excerpts. Results suggest that highly avoidant people engaged in less attachment behavior across both threatening and non-threatening situations. These findings have implications for the understanding of attachment-related processes and how working models of the self and others facilitate (or inhibit) the expression of attachment behavior.

Evaluation of the effects of pandemic-related fears on anxiety and depression: the mediating roles of traumatic stress and loneliness.

BACKGROUND: The detrimental mental health effects which emerged from COVID-19 have profoundly affected healthcare workers (HCWs) worldwide. The aim of this study was to investigate the mediating effects of traumatic stress and loneliness on the fears of contracting and dying from COVID-19, and anxiety and depression of HCWs during the pandemic. METHODS: A cross-sectional online survey was completed by HCWs in a province of Turkey. The Hospital Anxiety Depression Scale, Impact of Events Scale-Revised and numerical rating scales (for fears of COVID-19 and loneliness) were used and a bootstrap approach was used in the analyses with SPSS PROCESS macro software. RESULTS: Of the HCWs evaluated, 150 (34.4%) were doctors, with a mean duration of work experience of 10.6 ± 7.5 years. The results indicated that fear of contracting COVID-19 was directly related to anxiety (ß = 0.244, p < 0.001) and depression (ß = 0.135, p < 0.01) and that traumatic stress and loneliness mediated the relationships between the fear of contracting COVID-19 and anxiety (ß = 0.435, p < 0.001; ß = 0.235, p < 0.001, respectively) and depression (ß = 0.365, p < 0.001; ß = 0.294, p < 0.001, respectively). The fear of dying from COVID-19 was determined to be directly associated with anxiety (ß = 0.190, p < 0.001) but not with depression (ß = 0.066, p = 0.116), and traumatic stress and loneliness mediated the relationships between the fear of dying from COVID-19 and anxiety (ß = 0.476, p < 0.001; ß = 0.259, p < 0.001, respectively) and depression (ß = 0.400, p < 0.001; ß = 0.311, p < 0.001, respectively). CONCLUSIONS: The study results demonstrated the important roles of traumatic stress and loneliness in exacerbating the negative consequences of fears of COVID-19 on anxiety and depression, and provide insights for identifying HCWs at greater risk.

Predictive Model of the Relationship between Appearance, Eating Attitudes, and Physical Activity Behavior in Young People amid COVID-19.

This cross-sectional study conducted in Poland explored the relationship between the fear of negative appearance evaluations, eating disorders, and physical activity objectives, particularly during the COVID-19 pandemic. The Fear of Negative Appearance Evaluation Scale (FNAES), the Eating Attitude Test (EAT-26), and the Physical Activity Goals Inventory (IPAO) were administered to 644 participants (455 males with a mean age of 35.2 ± 6.2 years and 189 females with a mean age of 30.18 ± 5.7 years). This study explored the effects of gender, age, and body mass index (BMI) on FNAES, EAT-26, and IPAO scores. The results of this study demonstrated that females scored higher on fear of negative appearance, peaking at 41-50 years of age. Distinct BMI categories were associated with different negative appearance fear scores, eating attitudes, and physical activity objectives. Significant correlations were also found between the fear of negative appearance, dietary attitudes, and physical activity goals. Eating attitudes completely moderated the relationship between the fear of negative appearance and physical activity objectives. A significant interaction effect of age and body mass index on physical activity objectives was also revealed. These results highlight the relevance of considering gender, age, and body mass index when examining the associations between the fear of negative appearance, eating attitudes, and physical activity objectives.

Prejudice and Fear as Influences in Relation to a Successful Organ Donation - Experiences of Immigrants Living in Sweden.

OBJECTIVES: The purpose of this study was to determine whether fear and prejudice in relation to organ donation and the transplantation of organs may influence the decision to become an organ donor. MATERIALS AND METHODS: Data were collected through four group interviews using open-ended questions and qualitative content analysis. Forty participants, 16 males and 24 females from seven countries, participated in the focus group interviews. RESULTS: The analysis resulted in three main categories, and nine subcategories. Fears and prejudice caused by tradition and customs, approval of organ donation by family members, perception of the body as a gift from parents, the influence of religious leaders, knowledge about the religious understanding of organ donation, influence of social ambience on respondents, knowledge of the donation process in the healthcare system, including knowing about life after eventual organ donation, were some of predictors in the decision to agree to organ donation. CONCLUSION: More education on the factors that influence organ donation, more information in schools, health institutions and through the media, as well as more research with the aim of "dispelling" fears and prejudice about organ donation would significantly improve the current situation and result in a larger number of potential organ donors.

Histamine H1 receptors in dentate gyrus-projecting cholinergic neurons of the medial septum suppress contextual fear retrieval in mice.

Fear memory is essential for survival and adaptation, yet excessive fear memories can lead to emotional disabilities and mental disorders. Despite previous researches have indicated that histamine H1 receptor (H1R) exerts critical and intricate effects on fear memory, the role of H1R is still not clarified. Here, we show that deletion of H1R gene in medial septum (MS) but not other cholinergic neurons selectively enhances contextual fear memory without affecting cued memory by differentially activating the dentate gyrus (DG) neurons in mice. H1R in cholinergic neurons mediates the contextual fear retrieval rather than consolidation by decreasing acetylcholine release pattern in DG. Furthermore, selective knockdown of H1R in the MS is sufficient to enhance contextual fear memory by manipulating the retrieval-induced neurons in DG. Our results suggest that H1R in MS cholinergic neurons is critical for contextual fear retrieval, and could be a potential therapeutic target for individuals with fear-related disorders.

Memory Storage in Distributed Engram Cell Ensembles.

One of the most fascinating aspects of the brain is its ability to acquire new information from experience and retain it over time as memory. The search for physical correlates of memory, the memory engram, has been a longstanding priority in modern neurobiology. Advanced genetic approaches have led to the localization of engram cells in a few brain regions, including the hippocampus and cortex. Additionally, engram cells exhibit learning-induced, persistent modifications and have at least two states, active and silent. However, it has been hypothesized that engrams for a specific memory are distributed among multiple brain regions that are functionally connected, referred to as a unified engram complex. Recent tissue-clearing techniques have permitted high-throughput analyses of intact brain samples, which have been used to obtain a map of the engram complex for a contextual fear memory. Careful examination of these engram complex maps has revealed a potentially underappreciated contribution of subcortical regions, specifically thalamic nuclei, to memory function. These more holistic studies support the unified engram complex hypothesis for memory storage and have important implications for understanding dysfunctional engrams in the context of human disease.

Climbing Fiber Activation Induced by Footshock in the Cerebellar Vermis Lobule IV/V of Freely Moving Mice.

Parallel fibers (PFs) in the cerebellar cortex are involved in a series of coordinated responses in the fear conditioning paradigm induced by footshock. However, whether footshock can activate cerebellar climbing fibers (CFs) remains unclear. In this study, we recorded calcium (Ca2+) activity in CFs by optical fiber photometry in the cerebellar vermis lobule IV/V of freely moving mice with footshock stimulation. We found that the activation of CFs in the lobule IV/V was highly correlated with footshock stimulation but not with the sound stimulation used as a control. This result suggests that afferent information from CFs might be associated with the motor initiation of fear-related behaviors or fear emotion itself. Thus, our results suggest that a characteristic CF signal in the cerebellar cortex might be related to fear processing or footshock-related behaviors (such as startle responses or pain sensation).