Dissociation of behavioral and neural responses to provocation during reactive aggression in healthy adults with high versus low externalization

The externalizing spectrum describes a range of heterogeneous personality traits and behavioral patterns, primarily characterized by antisocial behavior, disinhibition, and substance (mis)use. In psychopathology, abnormalities in neural threat, reward responses and the impulse-control system may be responsible for these externalizing symptoms. Within the non-clinical range, mechanisms remain still unclear. In this fMRI-study, 61 healthy participants (31 men) from the higher versus lower range of the non-clinical variation in externalization (31 participants with high externalization) as assessed by the subscales disinhibition and meanness of the Triarchic-Psychopathy-Measure (TriPM) performed a monetary modified Taylor-Aggression-Paradigm (mTAP). This paradigm consisted of a mock competitive-reaction-time-task played against a fictional opponent with preprogrammed win- and lose-trials. In lose-trials, participants were provoked by subtraction of an amount of money between 0 and 90 cents. As a manipulation check, provocation induced a significant rise in behavioral aggression levels linked with an increased activation in the anterior cingulate cortex (ACC). High externalization predicted reduced ACC responses to provocation. However, high externalizing participants did not behave more aggressively than the low externalization group. Additionally, the high externalizing group showed a significantly lower positive affect while no group differences emerged for negative affect. In conclusion, high externalization in the non-clinical range was related to neural alterations in regions involved in affective decision-making as well as to changes in affect but did not lead to higher behavioral aggression levels in response to the mTAP. This is in line with previous findings suggesting that aberrations at multiple levels are essential for developing externalizing disorders

Stress Regulation in the Brain: Association with Cortisol Release, Modulation by Exposure Time, and Gender Differences

This thesis corroborates to a better understanding of the interplay between the brain and the hypothalamic-pituitary-adrenal (HPA) axis in response to acute psychosocial stress. Moreover, the impact of stress exposure time as well as gender differences were investigated. In a first step, a psychosocial stress paradigm suited for scanner environments – called ScanSTRESS – was evaluated and a hierarchical analysis strategy was developed. In the study proper, changes in brain activation, cortisol levels, affect, and heart rate responses to the improved ScanSTRESS protocol were assessed in 67 young, healthy participants (36 men, 31 women, all taking oral contraceptives; mean age 23.06 ± 3.14 years). Stress exposure led to significant increases in cortisol levels, heart rate, and negative affect ratings as well as activations and deactivations in (pre)limbic regions. When individual cortisol increases were used as covariate, stronger responses in the hippocampus, amygdala, medial prefrontal cortex, and cingulate gyrus were observed. Responses within the same regions predicted negative affect ratings throughout the protocol. Remarkably, an increasing deactivation over the two runs of ScanSTRESS was found, again, in the same structures. Regarding gender differences, responses of the hippocampus, amygdala, cingulate cortex, thalamus, and striatal structures were differentially associated with cortisol increases in women and men. For men, higher cortisol increases resulted in more activation of these striato-limbic structures whereas in women higher cortisol increases were associated with more deactivation

Testing the ecological validity of the Trier Social Stress Test: Association with real-life exam stress

The Trier Social Stress Test (TSST) is the most widely used laboratory stress protocol in psychoneuroendocrinology. Despite its popularity, surprisingly few attempts have been made to explore the ecological validity of the TSST. In the present study, 31 young healthy subjects (24 females) were exposed to the TSST about 4 weeks before completing an oral exam on a separate day. Salivary cortisol levels increased significantly in response to both stimuli (TSST: F(2.21, 66.33) =5.73, p =0.004; oral exam: F(1.98, 59.28)=4.38, p =0.017) with similar mean response curves and significant correlations between cortisol increases and areas under the response curves (increase: r=0.67; AUC: r =0.56; both p <= 0.01). Correspondingly, changes in positive and negative affect did also show significant correlations between conditions (increase: positive affect: r =0.36; negative affect: r=0.50; both: p <= 0.05; AUC: positive affect: r =0.81; negative affect: r =0.70; both p <= 0.01) while mean time course dynamics were significantly different (positive affect: F(2.55, 76.60)=10.15, p =0.001; negative affect: F(1.56, 46.82) =23.32, p =0.001), indicating that the oral exam had a more pronounced impact on affect than the TSST. Our findings provide new evidence for the view that cortisol as well as subjective stress responses to the TSST are indeed significantly associated with acute stress responses in real life. (C) 2016 Elsevier Ltd. All rights reserved

A graph neural network framework for causal inference in brain networks

A central question in neuroscience is how self-organizing dynamic interactions in the brain emerge on their relatively static structural backbone. Due to the complexity of spatial and temporal dependencies between different brain areas, fully comprehending the interplay between structure and function is still challenging and an area of intense research. In this paper we present a graph neural network (GNN) framework, to describe functional interactions based on the structural anatomical layout. A GNN allows us to process graph-structured spatio-temporal signals, providing a possibility to combine structural information derived from diffusion tensor imaging (DTI) with temporal neural activity profiles, like that observed in functional magnetic resonance imaging (fMRI). Moreover, dynamic interactions between different brain regions discovered by this data-driven approach can provide a multi-modal measure of causal connectivity strength. We assess the proposed model’s accuracy by evaluating its capabilities to replicate empirically observed neural activation profiles, and compare the performance to those of a vector auto regression (VAR), like that typically used in Granger causality. We show that GNNs are able to capture long-term dependencies in data and also computationally scale up to the analysis of large-scale networks. Finally we confirm that features learned by a GNN can generalize across MRI scanner types and acquisition protocols, by demonstrating that the performance on small datasets can be improved by pre-training the GNN on data from an earlier study. We conclude that the proposed multi-modal GNN framework can provide a novel perspective on the structure-function relationship in the brain. Accordingly this approach appears to be promising for the characterization of the information flow in brain networks

Higher allostatic load in work-related burnout: The Regensburg Burnout Project

Background Burnout and chronic work stress have been linked to various negative health outcomes. While the mechanisms underlying this interplay are still unclear, the allostatic load (AL) model was suggested to demonstrate a possible biological pathway. However, previous studies provided divergent results regarding the association between burnout and AL, probably also due to the heterogeneity of selected samples. Therefore, the aim of the present study was to examine differences in AL between a conceptually strictly specified group of individuals suffering from burnout (BO group) and a healthy comparison group (HC group). Methods After a multi-stage recruitment procedure with strict inclusion criteria based on burnout symptomatology and pathogenesis, the BO group (n = 56) was compared to the HC group (n = 65) regarding an index of AL. The AL-index included 14 parameters: high-sensitivity c-reactive protein (hsCRP), tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), fibrinogen, d-dimer, plasminogen activator inhibitor 1 (PAI-1), glycosylated hemoglobin (HbA1c), high-density lipoprotein (HDL) cholesterol, total cholesterol to HDL cholesterol ratio (TC/HDL), dehydroepiandrosterone-sulphate (DHEA-S), systolic blood pressure (SBP), diastolic blood pressure (DBP), waist-hip ratio (WHR), and body fat percentage. Results The BO group showed significantly higher AL-scores in comparison to the HC group. This effect remained significant after adjusting for sex, age, and smoking status. Additionally, burnout symptoms (assessed with the Maslach Burnout Inventory; MBI), MBI-subscales emotional exhaustion and depersonalization as well as chronic work stress (assessed with the effort-reward imbalance questionnaire) were significantly associated with higher AL-scores. Conclusions Consistent with our hypothesis, we detected higher AL-scores in the BO compared to the HC group, indicating a greater cumulative physiological burden in individuals suffering from burnout. Given the high heterogeneity in individuals experiencing burnout symptoms, future studies may focus on well-specified subgroups, when examining the association between burnout and psychophysiological dysregulations

Increasing Deactivation of Limbic Structures Over Psychosocial Stress Exposure Time

BACKGROUND: Understanding the interplay between central nervous system and hypothalamic-pituitary-adrenal axis responses to stress in humans is assumed to be essential to contribute to the central question of stress research, namely how stress can increase disease risk. Therefore, the present study used a neuroimaging stress paradigm to investigate the interplay of 3 stress response domains. Furthermore, we asked if the brain's stress response changes over exposure time. METHODS: In a functional magnetic resonance imaging study, changes in brain activation, cortisol levels, affect, and heart rate in response to an improved ScanSTRESS protocol were assessed in 67 young, healthy participants (31 females). RESULTS: Stress exposure led to significant increases in cortisol levels, heart rate, and negative affect ratings as well as to activations and deactivations in (pre)limbic regions. When cortisol increase was used as a covariate, stronger responses in the hippocampus, amygdala, medial prefrontal cortex, and cingulate gyrus were observed. Responses within the same regions predicted negative affect ratings. Remarkably, an increasing deactivation over the two ScanSTRESS runs was found, again, in the same structures. A reanalysis of an independent sample confirmed this finding. CONCLUSIONS: For the first time, reactions in a cluster of (pre)limbic structures was consistently found to be associated with changes in cortisol and negative affect. The same neural structures showed increasing deactivations over stress exposure time. We speculate that investigating possible associations between exposure-time effects in neural stress responses and stress-related interindividual differences (e.g., chronic stress) might be a promising new avenue in stress research

Comparing two psychosocial stress paradigms for imaging environments – ScanSTRESS and fNIRS-TSST: Correlation structures between stress responses

The present post-hoc analysis of two independent studies conducted in different laboratories aimed at comparing reactions of stress activation systems in response to two different psychosocial stress induction paradigms. Both paradigms are based on the Trier Social Stress Test (TSST) and suited for neuroimaging environments. In an in-depth analysis, data from 67 participants (36 men, 31 women) from a functional magnetic resonance imaging study implementing ScanSTRESS were compared with data from a functional near-infrared spectroscopy (fNIRS) study implementing the so-called ’fNIRS-TSST’ including 45 participants (8 men, 37 women). We tested the equivalence of correlation patterns between the stress response measures cortisol, heart rate, affect, and neural responses in the two samples. Moreover, direct comparisons of affective and neural responses were made. Similar correlation structures were identified for all stress activation systems, except for neural contrasts of paradigm conditions (stress vs. control) showing significant differences in association with cortisol, heart rate, and affective variables between the two samples. Furthermore, both stress paradigms elicited comparable affective and cortical stress responses. Apart from methodological differences (e.g., procedure, timing of the paradigms) the present analysis suggests that both paradigms are capable of inducing moderate acute psychosocial stress to a comparable extent with regard to affective and cortical stress responses. Moreover, similar association structures between different stress response systems were found in both studies. Thus, depending on the study objective and the respective advantages of each imaging approach, both paradigms have demonstrated their usefulness for future studies

Externalizing behavior in healthy young adults is associated with lower cortisol responses to acute stress and altered neural activation in the dorsal striatum

The externalizing spectrum is characterized by disinhibition, impulsivity, antisocial-aggressive behavior as well as substance (mis)use. Studies in forensic samples and mentally impaired children suggested that higher rates of externalization are linked to lower cortisol stress responses and altered affect-related neural activation. In this fMRI-study, we investigated whether externalizing behavior in healthy participants is likewise associated with altered cortisol responses and neural activity to stress. Following a quasi-experimental approach, we tested healthy participants (N = 61, 31 males) from the higher versus lower range of the non-clinical variation in externalization (31 participants with high externalization) as assessed by the subscales disinhibition and meanness of the Triarchic-Psychopathy-Measure. All participants were exposed to ScanSTRESS, a standardized psychosocial stress paradigm for scanner environments. In both groups, ScanSTRESS induced a significant rise in cortisol levels with the high externalization group showing significantly lower cortisol responses to stress than the low externalization group. This was mainly driven by males. Further, individual increases in cortisol predicted neural response differences between externalization groups, indicating more activation in the dorsal striatum in low externalization. This was primarily driven by females. In contrast, post-hoc analysis showed that hypothalamic-pituitary-adrenal axis hyporeactivity in males was associated with prefrontal and hippocampal activation. Our data substantiate that individuals from the general population high on externalization, show reduced cortisol stress responses. Furthermore, dorsal striatum activity as part of the mesolimbic system, known to be sensitive to environmental adversity, seems to play a role in externalization-specific cortisol stress responses. Beyond that, a modulating influence of gender was disclosed