Increased anger and stress and heightened connectivity between IFG and vmPFC in victims during social interaction.

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.

Acute stress selectively blunts reward anticipation but not consumption: An ERP study.

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.

Brain structure and function link to variation in biobehavioral dimensions across the psychopathological continuum.

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.

Cognitive Stress Regulation in Schizophrenia Patients and Healthy Individuals: Brain and Behavior.

Stress is an important factor in the development, triggering, and maintenance of psychotic symptoms. Still, little is known about the neural correlates of cognitively regulating stressful events in schizophrenia. The current study aimed at investigating the cognitive down-regulation of negative, stressful reactions during a neuroimaging psychosocial stress paradigm (non-regulated stress versus cognitively regulated stress). In a randomized, repeated-measures within-subject design, we assessed subjective reactions and neural activation in schizophrenia patients (SZP) and matched healthy controls in a neuroimaging psychosocial stress paradigm. In general, SZP exhibited an increased anticipation of stress compared to controls (p = 0.020). During non-regulated stress, SZP showed increased negative affect (p = 0.033) and stronger activation of the left parietal operculum/posterior insula (p < 0.001) and right inferior frontal gyrus/anterior insula (p = 0.005) than controls. Contrarily, stress regulation compared to non-regulated stress led to increased subjective reactions in controls (p = 0.003) but less deactivation in SZP in the ventral anterior cingulate cortex (p = 0.027). Our data demonstrate stronger reactions to and anticipation of stress in patients and difficulties with cognitive stress regulation in both groups. Considering the strong association between mental health and stress, the investigation of cognitive regulation in individuals vulnerable to stress, including SZP, has crucial implications for improving stress intervention trainings.

Integrating the pattern of negative emotion processing and acute stress response with childhood stress among healthy young adults.

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.

Brain network changes in adult victims of violence.

Introduction: Stressful 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 methods: The 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. Results: Our 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. Conclusion: The results showed that individuals who identify themselves as victim demonstrated significant differences in all considered networks, both within- and between-network.

Blunted reward responsiveness prospectively predicts emotional distress when exposed to a naturalistic stressor.

Both stress and blunted reward responsiveness have been identified as core risk factors of depression. Whether blunted reward responsiveness increases psychological vulnerability to real-life stress from a dynamic perspective (from stress reactivity to recovery) has not been investigated. By utilizing a real-world stressful event (i.e. the final examination), this study aimed to explore the role of reward responsiveness in the stress-emotional distress relationship during stress reactivity and recovery phases. We followed 57 undergraduates with three assessments, from six weeks before examination weeks (T1, baseline), one day before the examinations (T2) to two weeks after the examinations (T3), therefore, covering stress reactivity (T1 to T2) and recovery (T2 to T3) phases. At baseline, reward responsiveness was measured as the Reward Positivity (RewP) in the doors task. Stress and emotional distress (anxiety and depression) were reported at T1, T2 and T3 to capture their dynamic changes. Results showed that self-report stress levels significantly increased from T1 to T2 (stress reactivity phase) and decreased from T2 to T3 (stress recovery phase). Furthermore, blunted reward responsiveness at baseline prospectively predicted emotional distress during the stress reactivity phase but not the recovery phase. Specifically, during the stress reactivity phase, higher perceived stress was associated with greater anxiety and depression only in participants with relatively smaller residual RewP amplitudes but not in participants with relatively larger residual RewP amplitudes. Our study demonstrated that a blunted reward responsiveness is a vulnerable factor of depression, especially when exposed to stress. Our findings provide insights into prevention and intervention for stress-related disturbance.

Neural correlates of repetitive negative thinking: Dimensional evidence across the psychopathological continuum.

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.

Pre- and postnatal antibiotic exposure and risk of developing attention deficit hyperactivity disorder-A systematic review and meta-analysis combining evidence from human and animal studies.

This study investigated the effects of early antibiotic exposure on ADHD risk by (1) integrating meta-analytical evidence from human observational studies examining the association between prenatal or early postnatal antibiotic exposure on the risk of developing ADHD; and (2) reviewing evidence from experimental animal studies on the effects of early antibiotic exposure on behavior. Sixteen human studies and five rodent studies were reviewed. A quantitative meta-analysis with 10 human studies indicated an increased risk for ADHD after prenatal antibiotic exposure (summary effect estimate Hazard Ratio (HR) 1.23, 95% CI 1.09-1.38; N = 2,398,475 subjects) but not after postnatal exposure within the first two years of life (summary effect estimate HR 1.12, 95% CI 0.95-1.32; N = 1,863,867 subjects). The rodent literature suggested that peri-natal antibiotic exposure has effects on social behavior, anxiety and aggression, alongside changes in gut microbial composition. Human and rodent findings thus suggest prenatal antibiotic exposure as a possible risk factor for ADHD, and suggest that an early disruption of the gut microbiome by antibiotics may interfere with neurodevelopment.

Reappraisal and empathic perspective-taking - More alike than meets the eyes.

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.

Correction: Protocol of the Healthy Brain Study: An accessible resource for understanding the human brain and how it dynamically and individually operates in its bio-social context.

[This corrects the article DOI: 10.1371/journal.pone.0260952.].

Hippocampal-Medial Prefrontal Event Segmentation and Integration Contribute to Episodic Memory Formation.

How do we encode our continuous life experiences for later retrieval? Theories of event segmentation and integration suggest that the hippocampus binds separately represented events into an ordered narrative. Using a functional Magnetic Resonance Imaging (fMRI) movie watching-recall dataset, we quantified two types of neural similarities (i.e., "activation pattern" similarity and within-region voxel-based "connectivity pattern" similarity) between separate events during movie watching and related them to subsequent retrieval of events as well as retrieval of sequential order. We demonstrated that compared with forgotten events, successfully remembered events were associated with distinct "activation patterns" in the hippocampus and medial prefrontal cortex. In contrast, similar "connectivity pattern" between events were associated with memory formation and were also relevant for retaining events in the correct order. We applied the same approaches to an independent movie watching fMRI dataset as validation and highlighted again the role of hippocampal activation pattern and connectivity pattern in memory formation. We propose that distinct activation patterns represent neural segmentation of events, while similar connectivity patterns encode context information and, therefore, integrate events into a narrative. Our results provide novel evidence for the role of hippocampal-medial prefrontal event segmentation and integration in episodic memory formation of real-life experience.

Protocol of the Healthy Brain Study: An accessible resource for understanding the human brain and how it dynamically and individually operates in its bio-social context.

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.

Differences in executive abilities rather than associative processes contribute to memory development.

Children's learning capabilities change while growing up. One framework that describes the cognitive and neural development of children's growing learning abilities is the two-component model. It distinguishes processes that integrate separate features into a coherent memory representation (associative component) and executive abilities, such as elaboration, evaluation, and monitoring, that support memory processing (strategic component). In an fMRI study using an object-location association paradigm, we investigated how the two components influence memory performance across development. We tested children (10-12 years, n = 31), late adolescents (18 years, n = 29), and adults (25+ years, n = 30). For studying the associative component, we also probed how the utilisation of prior knowledge (schemas) facilitates memory across age groups. Children had overall lower retrieval performance, while adolescents and adults did not differ from each other. All groups benefitted from schemas, but this effect did not differ between groups. Performance differences between groups were associated with deactivation of the dorsal medial prefrontal cortex (dmPFC), which in turn was linked to executive functioning. These patterns were stronger in adolescents and adults and seemed absent in children. Thus, the children's executive system, the strategic component, is not as mature and thus cannot facilitate memory performance in the same way as in adolescents/adults. In contrast, we did not find age-related differences in the associative component; with activity in the angular gyrus predicting memory performance systematically across groups. Overall, our results suggest that differences of executive rather than associative abilities explain memory differences between children, adolescents, and adults.

Dynamic Transitions between Neural States Are Associated with Flexible Task Switching during a Memory Task.

Flexible behavior requires switching between different task conditions. It is known that such task switching is associated with costs in terms of slowed RT, reduced accuracy, or both. The neural correlates of task switching have usually been studied by requiring participants to switch between distinct task conditions that recruit different brain networks. Here, we investigated the transition of neural states underlying switching between two opposite memory-related processes (i.e., memory retrieval and memory suppression) in a memory task. We investigated 26 healthy participants who performed a think/no-think task while being in the fMRI scanner. Behaviorally, we show that it was more difficult for participants to suppress unwanted memories when a no-think was preceded by a think trial instead of another no-think trial. Neurally, we demonstrate that think-no-think switches were associated with an increase in control-related and a decrease in memory-related brain activity. Neural representations of task condition, assessed by decoding accuracy, were lower immediately after task switching compared with the nonswitch transitions, suggesting a switch-induced delay in the neural transition toward the required task condition. This suggestion is corroborated by an association between condition-specific representational strength and condition-specific performance in switch trials. Taken together, we provided neural evidence from the time-resolved decoding approach to support the notion that carryover of the previous task set activation is associated with the switching cost, leading to less successful memory suppression.

Neuroinflammation in cognitive decline post-cardiac surgery (the FOCUS study): an observational study protocol.

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.

The relationship between childhood stress and distinct stages of dynamic behavior monitoring in adults: neural and behavioral correlates.

Childhood adversity is a major risk factor for emotional and cognitive disorders later in adulthood. Behavior monitoring, one of the most important components of cognitive control, plays a crucial role in flexible interaction with the environment. Here, we test a novel conceptual model discriminating between two distinct dimensions of childhood adversity (i.e. deprivation and threat) and examine their relations to dynamic stages of behavior monitoring. Sixty young healthy adults participated in this study using event-related potentials and the dynamic stages of behavior monitoring including response inhibition, error detection and post-error adjustments were investigated in a classical Go/NoGo task. Multiple regression analyses revealed that participants with higher severity of childhood adversity recruited more controlled attention, as indicated by larger (more negative) conflict detection-related NoGo-N2 amplitudes and larger (more negative) error detection-related error-related negativity amplitudes. Higher severity of childhood abuse (an indicator of threat) was related to smaller (less positive) error appraisal-related error positivity amplitudes on the neural level and subsequently lower post-error accuracy on the behavioral level. These results suggested that prefrontal-supported controlled attention is influenced by universal adversity in childhood while the error-related behavioral adjustment is mainly affected by childhood abuse, indicating the dimensions of deprivation and threat are at least partially distinct.

Test-retest reliability of emotion regulation networks using fMRI at ultra-high magnetic field.

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.

Measuring inter-individual differences in stress sensitivity during MR-guided prostate biopsy.

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.