Associations between cortisol stress responses and limbic volume and thickness in young adults: an exploratory study

The investigation of the relationship between neural measures of limbic structures and hypothalamic pituitary adrenal axis responses to acute stress exposure in healthy young adults has so far focused in particular on task-based and resting state functional connectivity studies. Thus, the present study examined the association between limbic volume and thickness measures and acute cortisol responses to the psychosocial stress paradigm ScanSTRESS. Using Permutation Analysis of Linear Models controlling for sex, age, and total brain volume, the associations between (sex-specific) cortisol increases and human connectome project style anatomical variables of limbic structures (i.e., volume and thickness) were investigated in 66 healthy and young (18-33 years) subjects (35 men, 31 women taking oral contraceptives). In addition, exploratory (sex-specific) bivariate correlations between cortisol increases and structural measures were conducted. The present data provide interesting new insights into the involvement of striato-limbic structures in psychosocial stress processing, suggesting that acute cortisol stress responses are also associated with mere structural measures of the human brain. Thus, our pre-liminary findings suggest that not only situation- and contextdependent reactions of the limbic system (i.e., blood oxygenation level dependent reactions) are related to acute (sex-specific) cortisol stress responses, but also basal and somewhat more constant structural measures. Our study hereby paves the way for further analyses in this context and highlights the relevance of the topic

Associations between cortisol stress responses and limbic volume and thickness in young adults: An exploratory study

The investigation of the relationship between neural measures of limbic structures and hypothalamic pituitary adrenal axis responses to acute stress exposure in healthy young adults has so far focused in particular on task-based and resting state functional connectivity studies. Thus, the present study examined the association between limbic volume and thickness measures and acute cortisol responses to the psychosocial stress paradigm ScanSTRESS. Using Permutation Analysis of Linear Models controlling for sex, age and total brain volume, the associations between (sex-specific) cortisol increases and human connectome project style anatomical variables of limbic structures (i.e. volume and thickness) were investigated in 66 healthy and young (18–33 years) subjects (35 men, 31 women taking oral contraceptives). In addition, exploratory (sex-specific) bivariate correlations between cortisol increases and structural measures were conducted. The present data provide interesting new insights into the involvement of striato-limbic structures in psychosocial stress processing, suggesting that acute cortisol stress responses are also associated with mere structural measures of the human brain. Thus, our preliminary findings suggest that not only situation- and context-dependent reactions of the limbic system (i.e. blood oxygenation level-dependent reactions) are related to acute (sex-specific) cortisol stress responses but also basal and somewhat more constant structural measures. Our study hereby paves the way for further analyses in this context and highlights the relevance of the topic

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

Sex-Specific Interaction Between Cortisol and Striato-Limbic Responses to Psychosocial Stress

Although women and men differ in psychological and endocrine stress responses as well as prevalence rates of stress-related disorders, knowledge on sex differences regarding stress regulation in the brain is scarce.Therefore, we performed an in-depth analysis of data from 67 healthy participants (31 women, taking oral contraceptives), who were exposed to the ScanSTRESS paradigm in an fMRI study. Changes in cortisol, affect, heart rate, and neural activation in response to psychosocial stress were examined in women and men as well as potential sex-specific interactions between stress response domains.Stress exposure led to significant cortisol increases with men exhibiting higher levels than women. Dependent on sex, cortisol elevations were differently associated with stress-related responses in striato-limbic structures: Higher increases were associated with activations in men but with deactivations in women. Regarding affect or heart rate responses, no sex differences emerged.Although women and men differ in their overall stress reactivity, our findings do not support the idea of distinct neural networks as base of this difference. Instead, we found differential stress reactions for women and men in identical structures. We propose considering quantitative predictors like sex-specific cortisol increases when exploring neural response differences of women and men

Neural responses to acute stress predict chronic stress perception in daily life over 13 months

The importance of amygdala, hippocampus, and medial prefrontal cortex (mPFC) for the integration of neural, endocrine, and affective stress processing was shown in healthy participants and patients with stress-related disorders. The present manuscript which reports on one study-arm of the LawSTRESS project, aimed at investigating the predictive value of acute stress responses in these regions for biopsychological consequences of chronic stress in daily life. The LawSTRESS project examined law students either in preparation for their first state examination (stress group [SG]) or in the mid-phase of their study program (control group [CG]) over 13 months. Ambulatory assessments comprising perceived stress measurements and the cortisol awakening response (CAR) were administered on six sampling points (t1 = − 1 year, t2 = − 3 months, t3 = − 1 week, t4 = exam, t5 =  + 1 week, t6 =  + 1 month). In a subsample of 124 participants (SG: 61; CG: 63), ScanSTRESS was applied at baseline. In the SG but not in the CG, amygdala, hippocampus, and (post-hoc analyzed) right mPFC activation changes during ScanSTRESS were significantly associated with the trajectory of perceived stress but not with the CAR. Consistent with our finding in the total LawSTRESS sample, a significant increase in perceived stress and a blunted CAR over time could be detected in the SG only. Our findings suggest that more pronounced activation decreases of amygdala, hippocampus, and mPFC in response to acute psychosocial stress at baseline were related to a more pronounced increase of stress in daily life over the following year

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

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

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