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Abstract Self-identification as a victim of violence may lead to increased negative emotions and stress and thus, may change both structure and function of the underlying neural network(s). In a trans-diagnostic sample of individuals who identified themselves as victims of violence and a matched control group with no prior exposure to violence, we employed a social exclusion paradigm, the Cyberball task, to stimulate the re-experience of stress. Participants were partially excluded in the ball-tossing game without prior knowledge. We analyzed group differences in brain activity and functional connectivity during exclusion versus inclusion in exclusion-related regions. The victim group showed increased anger and stress levels during all conditions. Activation patterns during the task did not differ between groups but an enhanced functional connectivity between the IFG and the right vmPFC distinguished victims from controls during exclusion. This effect was driven by aberrant connectivity in victims during inclusion rather than exclusion, indicating that victimization affects emotional responses and inclusion-related brain connectivity rather than exclusion-related brain activity or connectivity. Victims may respond differently to the social context itself. Enhanced negative emotions and connectivity deviations during social inclusion may depict altered social processing and may thus affect social interactions.

Stress-induced dysfunction of reward processing is documented to be a critical factor associated with mental illness. Although many studies have attempted to clarify the relationship between stress and reward, few studies have investigated the effect of acute stress on the temporal dynamics of reward processing. The present study applied event-related potentials (ERP) to examine how acute stress differently influences reward anticipation and consumption. In this study, seventy-eight undergraduates completed a two-door reward task following a Trier Social Stress Task (TSST) or a placebo task. The TSST group showed higher cortisol levels, perceived stress, anxiety, and negative affect than the control group. For the control group, a higher magnitude of reward elicited a reduced cue-N2 but increased stimulus-preceding negativity (SPN), suggesting that controls were sensitive to reward magnitude. In contrast, these effects were absent in the stress group, suggesting that acute stress reduces sensitivity to reward magnitude during the anticipatory phase. However, the reward positivity (RewP) and P3 of both groups showed similar patterns, which suggests that acute stress has no impact on reward responsiveness during the consummatory phase. These findings suggest that acute stress selectively blunts sensitivity to reward magnitude during the anticipatory rather than the consummatory phase.

In line with the Research Domain Criteria (RDoC) , we set out to investigate the brain basis of psychopathology within a transdiagnostic, dimensional framework. We performed an integrative structural-functional linked independent component analysis to study the relationship between brain measures and a broad set of biobehavioral measures in a sample (n = 295) with both mentally healthy participants and patients with diverse non-psychotic psychiatric disorders (i.e. mood, anxiety, addiction, and neurodevelopmental disorders). To get a more complete understanding of the underlying brain mechanisms, we used gray and white matter measures for brain structure and both resting-state and stress scans for brain function. The results emphasize the importance of the executive control network (ECN) during the functional scans for the understanding of transdiagnostic symptom dimensions. The connectivity between the ECN and the frontoparietal network in the aftermath of stress was correlated with symptom dimensions across both the cognitive and negative valence domains, and also with various other health-related biological and behavioral measures. Finally, we identified a multimodal component that was specifically associated with the diagnosis of autism spectrum disorder (ASD). The involvement of the default mode network, precentral gyrus, and thalamus across the different modalities of this component may reflect the broad functional domains that may be affected in ASD, like theory of mind, motor problems, and sensitivity to sensory stimuli, respectively. Taken together, the findings from our extensive, exploratory analyses emphasize the importance of a dimensional and more integrative approach for getting a better understanding of the brain basis of psychopathology.

IntroductionStressful experiences such as violence can affect mental health severely. The effects are associated with changes in structural and functional brain networks. The current study aimed to investigate brain network changes in four large-scale brain networks, the default mode network, the salience network, the fronto-parietal network, and the dorsal attention network in self-identified victims of violence and controls who did not identify themselves as victims.Materials and methodsThe control group (n = 32) was matched to the victim group (n = 32) by age, gender, and primary psychiatric disorder. Sparse inverse covariance maps were derived from functional resting-state measurements and from T1 weighted structural data for both groups.ResultsOur data underlined that mostly the salience network was affected in the sample of self-identified victims. In self-identified victims with a current psychiatric diagnosis, the dorsal attention network was mostly affected underlining the potential role of psychopathological alterations on attention-related processes.ConclusionThe results showed that individuals who identify themselves as victim demonstrated significant differences in all considered networks, both within- and between-network.

Childhood adversity might impair corticolimbic brain regions, which play a crucial role in emotion processing and the acute stress response. The dimensional model of childhood adversity proposed that deprivation and threat dimensions might associated with individuals’ development through different mechanisms. However, few studies have explored the relationship between different dimensions of childhood stress, emotion processing, and acute stress reactivity despite the overlapping brain regions of the last two. With the aid of the event-related potentials technique, we explore whether negative emotion processing, which might be particularly relevant for adaptive stress responding among individuals with adverse childhood experience, mediates the relationship between dimensional childhood stress and acute stress response. Fifty-one young adults completed a free-viewing task to evaluate neural response to negative stimuli measured by late positive potential (LPP) of ERPs (Event-related potentials). On a separate day, heart rate and salivary cortisol were collected during a social-evaluative stress challenge (i.e. TSST, Trier Social Stress Test). After the TSST, the childhood trauma questionnaire was measured to indicate the level of abuse (as a proxy of threat) and neglect (as a proxy of deprivation) dimensions. Multiple linear regression and mediation analysis were used to explore the relationship among childhood stress, emotion processing, and acute stress response. Higher level of childhood abuse (but not neglect) was distinctly related to smaller LPP amplitudes to negative stimuli, as well as smaller heart rate reactivity to acute stress. For these participants, smaller LPP amplitudes were linked with smaller heart rate reactivity to acute stress. Furthermore, decreased LPP amplitudes to negative stimuli mediated the relationship between higher level of childhood abuse and blunted heart rate reactivity to stress. Consistent with the dimensional model of childhood stress, our study showed that childhood abuse is distinctly associated with neural as well as physiological response to threat. Furthermore, the blunted neural response to negative stimuli might be the underlying mechanism in which childhood abuse leads to the blunted acute stress response. Considering that all the participants are healthy in the present study, the blunted processing of negative stimuli might rather reflect adaptation instead of vulnerability, in order to prevent stress overshooting in the face of early-life threatening experiences.

Emotion regulation and empathy represent highly intertwined psychological processes sharing common conceptual ground. Despite the wealth of research in these fields, the joint and distinct functional nature and topological features of these constructs have not yet been investigated using the same experimental approach. This study investigated the common and distinct neural correlates of emotion regulation and empathy using a meta-analytic approach. The regions that were jointly activated were then characterized using meta-analytic connectivity modeling and functional decoding of metadata terms. The results revealed convergent activity within the ventrolateral and dorsomedial prefrontal cortex as well as temporal regions. The functional decoding analysis demonstrated that emotion regulation and empathy were related to highly similar executive and internally oriented processes. This synthesis underlining strong functional and neuronal correspondence between emotion regulation and empathy could (i) facilitate greater integration of these two separate lines of literature, (ii) accelerate progress toward elucidating the neural mechanisms that support social cognition, and (iii) push forward the development of a common theoretical framework for these psychological processes essential to human social interactions.

Repetitive negative thinking (RNT) captures an important transdiagnostic factor that predisposes to a maladaptive stress response and contributes to diverse psychiatric disorders. Although RNT can best be seen as a continuous symptom dimension that cuts across boundaries from health to various psychiatric disorders, the neural mechanisms underlying RNT have almost exclusively been studied in health and stress-related disorders, such as depression and anxiety disorders. We set out to study RNT from a large-scale brain network perspective in a diverse population consisting of healthy subjects and patients with a broader range of psychiatric disorders. We studied 46 healthy subjects along with 153 patients with a stress-related and/or neurodevelopmental disorder. We focused on three networks, that are associated with RNT and diverse psychiatric disorders: the salience network, default mode network (DMN) and frontoparietal network (FPN). We investigated the relationship of RNT with both network connectivity strength at rest and with the stress-induced changes in connectivity. Across our whole sample, the level of RNT was positively associated with the connectivity strength of the left FPN at rest, but negatively associated with stress-induced changes in DMN connectivity. These findings may reflect an upregulation of the FPN in an attempt to divert attention away from RNT, while the DMN result may reflect a less flexible adaptation to stress, related to RNT. Additionally, we discuss how our findings fit into the non-invasive neurostimulation literature. Taken together, our results provide initial insight in the neural mechanisms of RNT across the spectrum from health to diverse psychiatric disorders.

Abstract People often experience high level of distress during invasive interventions, which may exceed their coping abilities. This may be in particular evident when confronted with the suspicion of cancer. Taking the example of prostate biopsy sampling, we aimed at investigating the impact of an MRI guided prostate biopsy on the acute stress response and its mechanistic basis. We recruited 20 men with a clinical suspicion of prostate cancer. Immediately before an MRI guided biopsy procedure, we conducted fMRI in the same scanner to assess resting-state brain connectivity. Physiological and hormonal stress measures were taken during the procedure and associated with questionnaires, hair cortisol levels and brain measures to elucidate mechanistic factors for elevated stress. As expected, patients reported a stress-related change in affect. Decreased positive affect was associated with higher hair but not saliva cortisol concentration. Stronger use of maladaptive emotion regulation techniques, elevated depression scores and higher within-salience-network connectivity was associated with stronger increase in negative affect and/or decrease of positive affect during the procedure. While being limited in its generalization due to age, sample size and gender, our proof of concept study demonstrates the utility of real-life stressors and large-scale brain network measures in stress regulation research with potential impact in clinical practice.

Given the importance of emotion regulation in affective disorders, emotion regulation is at the focus of attempts to identify brain biomarkers of disease risk, treatment response, and brain development. However, to be useful as an indicator for individual characteristics of brain functions – particularly as a biomarker in a clinical context – ensuring reliability is a key challenge. Here, we systematically evaluated test-retest reliability of task-based functional magnetic resonance imaging (fMRI) activity within neural networks associated with emotion generation and regulation across three sessions. Acquiring fMRI data at ultra-high field (7T), we examined region- and voxel-wise test-retest reliability of brain activity in response to a well-established emotion regulation task for predefined region-of-interests (ROIs) implicated in four neural networks. Test-retest reliability varied considerably across the emotion regulation networks and respective ROIs. However, core emotion regulation regions, including the ventrolateral and dorsolateral prefrontal cortex (vlPFC and dlPFC) as well as the middle temporal gyrus (MTG) showed high reliability. Our findings thus support the role of these prefrontal and temporal regions as promising candidates for the study of individual differences in emotion regulation as well as for neurobiological biomarkers in clinical neuroscience research.

Introduction Postoperative cognitive dysfunction occurs frequently after coronary artery bypass grafting (CABG). The underlying mechanisms remain poorly understood, but neuroinflammation might play a pivotal role. We hypothesise that systemic inflammation induced by the surgical trauma could activate the innate immune (glial) cells of the brain. This could lead to an exaggerated neuroinflammatory cascade, resulting in neuronal dysfunction and loss of neuronal cells. Therefore, the aims of this study are to assess neuroinflammation in vivo presurgery and postsurgery in patients undergoing major cardiac surgery and investigate whether there is a relationship of neuroinflammation to cognitive outcomes, changes to brain structure and function, and systemic inflammation.Methods and analysis The FOCUS study is a prospective, single-centre observational study, including 30 patients undergoing elective on-pump CABG. Translocator protein (TSPO) positron emission tomography neuroimaging will be performed preoperatively and postoperatively using the second generation tracer 18F-DPA-714 to assess the neuroinflammatory response. In addition, a comprehensive cerebral MRI will be performed presurgery and postsurgery, in order to discover newly developed brain and vascular wall lesions. Up to 6 months postoperatively, serial extensive neurocognitive assessments will be performed and blood will be obtained to quantify systemic inflammatory responses and peripheral immune cell activation.Ethics and dissemination Patients do not benefit directly from engaging in the study, but imaging neuroinflammation is considered safe and no side effects are expected. The study protocol obtained ethical approval by the Medical Research Ethics Committee region Arnhem-Nijmegen. This work will be published in peer-reviewed international medical journals and presented at medical conferences.Trial registration number NCT04520802.

Background: The Covid-19 pandemic has led to drastic public health measures with a substantial impact on the individual. Previous studies reported elevated levels of stress, anxiety, and depression in the general population as a consequence of pandemic-related public health measures. In vulnerable individuals, exposure to an uncontrolled global stressor like the Covid-19 pandemic might be felt as particularly threatening. Methods: A population of 127 healthy individuals that expressed increased trait anxiety (HADS ≥ 8) already before the outbreak of the pandemic were tested on state and trait anxiety, stress and depression before and four weeks after the outbreak of the pandemic in the Netherlands. Online questionnaires were administered between April 16 and April 23, 2020. Results: We observed an increase in state anxiety (STAI) during the pandemic but no change in depression. Yet, trait anxiety (STAI) before the pandemic did not predict the increase in state anxiety during the pandemic. Further, state anxiety during the pandemic was not associated with being in contact with an infected person, having symptoms of Covid-19, protective behavior, or degree of social isolation when controlling for state anxiety before the outbreak of the pandemic. However, maladaptive emotion regulation strategies measured before the pandemic predicted state anxiety and perceived stress during the pandemic, while adaptive strategies had no association with anxiety during the pandemic. Conclusion: Reducing learned helplessness and self-blaming to prevent maladaptive emotion regulation strategies like giving up and self-devaluation might be more beneficial than training adaptive strategies. Limitations: Time variation in baseline measurements.

The endeavor to understand the human brain has seen more progress in the last few decades than in the previous two millennia. Still, our understanding of how the human brain relates to behavior in the real world and how this link is modulated by biological, social, and environmental factors is limited. To address this, we designed the Healthy Brain Study (HBS), an interdisciplinary, longitudinal, cohort study based on multidimensional, dynamic assessments in both the laboratory and the real world. Here, we describe the rationale and design of the currently ongoing HBS. The HBS is examining a population-based sample of 1,000 healthy participants (age 30-39) who are thoroughly studied across an entire year. Data are collected through cognitive, affective, behavioral, and physiological testing, neuroimaging, bio-sampling, questionnaires, ecological momentary assessment, and real-world assessments using wearable devices. These data will become an accessible resource for the scientific community enabling the next step in understanding the human brain and how it dynamically and individually operates in its bio-social context. An access procedure to the collected data and bio-samples is in place and published on https://www.healthybrainstudy.nl/en/data-and-methods/access. Trail registration: https://www.trialregister.nl/trial/7955.

Memories are not stored as static engrams, but as dynamic representations affected by processes occurring after initial encoding. Previous studies revealed changes in activity and mnemonic representations in visual processing areas, parietal lobe, and hippocampus underlying repeated retrieval and suppression. However, these neural changes are usually induced by memory modulation immediately after memory formation. Here, we investigated 27 healthy participants with a two-day functional Magnetic Resonance Imaging study design to probe how established memories are dynamically modulated by retrieval and suppression 24 h after learning. Behaviorally, we demonstrated that established memories can still be strengthened by repeated retrieval. By contrast, repeated suppression had a modest negative effect, and suppression-induced forgetting was associated with individual suppression efficacy. Neurally, we demonstrated item-specific pattern reinstatements in visual processing areas, parietal lobe, and hippocampus. Then, we showed that repeated retrieval reduced activity amplitude in the ventral visual cortex and hippocampus, but enhanced the distinctiveness of activity patterns in the ventral visual cortex and parietal lobe. Critically, reduced activity was associated with enhanced representation of idiosyncratic memory traces in the ventral visual cortex and precuneus. In contrast, repeated memory suppression was associated with reduced lateral prefrontal activity, but relative intact mnemonic representations. Our results replicated most of the neural changes induced by memory retrieval and suppression immediately after learning and extended those findings to established memories after initial consolidation. Active retrieval seems to promote episode-unique mnemonic representations in the neocortex after initial encoding but also consolidation.

Abstract Background In-vivo observations of neural processes during human aggressive behavior are difficult to obtain, limiting the number of studies in this area. To address this gap, the present study implemented a social reactive aggression paradigm in 29 healthy men, employing non-violent provocation in a two-player game to elicit aggressive behavior in fMRI settings. Results Participants responded more aggressively after high provocation reflected in taking more money from their opponents. Comparing aggression trials after high provocation to those after low provocation revealed activations in neural circuits involved in aggression: the medial prefrontal cortex (mPFC), the orbitofrontal cortex (OFC), the dorsolateral prefrontal cortex (dlPFC), the anterior cingulate cortex (ACC), and the insula. In general, our findings indicate that aggressive behavior activates a complex, widespread brain network, reflecting a cortico-limbic interaction and overlapping with circuits underlying negative emotions and conflicting decision-making. Brain activation during provocation in the OFC was associated with the degree of aggressive behavior in this task. Conclusion Therefore, data suggest there is greater susceptibility for provocation, rather than less inhibition of aggressive tendencies, in individuals with higher aggressive responses. This further supports the hypothesis that reactive aggression can be seen as a consequence of provocation of aggressive emotional responses and parallel evaluative regulatory processes mediated mainly by the insula and prefrontal areas (OFC, mPFC, dlPFC, and ACC) respectively.

Aversive odors are highly salient stimuli that serve a protective function. Thus, emotional reactions elicited by negative odors may be hardly influenceable. We aim to elucidate if negative mood induced by negative odors can be modulated automatically by positively valenced stimuli. We included 32 healthy participants (16 men) in an fMRI design combining aversive and neutral olfactory stimuli with positive and neutral auditory stimuli to test the influence of aversive olfactory stimuli on subjective emotional state and brain activation when combined with positive and neutral auditory stimuli. The behavioral results show an interaction of negative olfactory stimuli on ratings of disgust, perceived valence of music, and subjective affective state, while positive auditory stimulation did not show this interaction. On a neuronal level, we observed main effects for auditory and olfactory stimulation, which are largely congruent with previous literature. However, the pairing of both stimuli was associated with attenuated brain activity in a set of brain areas (supplementary motor area, temporal pole, superior frontal gyrus) which overlaps with multisensory processing areas and pave the way for automatic emotion regulation. Our behavioral results and the integrated neural patterns provide evidence of predominance of olfaction in processing of affective rivalry from multiple sensory modalities.

Anhedonia, reduced positive affect and enhanced negative affect are integral characteristics of major depressive disorder (MDD). Emotion dysregulation, e.g. in terms of different emotion processing deficits, has consistently been reported. The aim of the present study was to investigate mood changes in depressive patients using a multidimensional approach for the measurement of emotional reactivity to mood induction procedures. Experimentally, mood states can be altered using various mood induction procedures. The present study aimed at validating two different positive mood induction procedures in patients with MDD and investigating which procedure is more effective and applicable in detecting dysfunctions in MDD. The first procedure relied on the presentation of happy vs. neutral faces, while the second used funny vs. neutral cartoons. Emotional reactivity was assessed in 16 depressed and 16 healthy subjects using self-report measures, measurements of electrodermal activity and standardized analyses of facial responses. Positive mood induction was successful in both procedures according to subjective ratings in patients and controls. In the cartoon condition, however, a discrepancy between reduced facial activity and concurrently enhanced autonomous reactivity was found in patients. Relying on a multidimensional assessment technique, a more comprehensive estimate of dysfunctions in emotional reactivity in MDD was available than by self-report measures alone and this was unsheathed especially by the mood induction procedure relying on cartoons. The divergent facial and autonomic responses in the presence of unaffected subjective reactivity suggest an underlying deficit in the patients' ability to express the felt arousal to funny cartoons. Our results encourage the application of both procedures in functional imaging studies for investigating the neural substrates of emotion dysregulation in MDD patients. Mood induction via cartoons appears to be superior to mood induction via faces and autobiographical material in uncovering specific emotional dysfunctions in MDD.