Jens C. Pruessner

Hippocampus and amygdala volumes from magnetic resonance images in children: Assessing accuracy of FreeSurfer and FSL against manual segmentation.

The volumetric quantification of brain structures is of great interest in pediatric populations because it allows the investigation of different factors influencing neurodevelopment. FreeSurfer and FSL both provide frequently used packages for automatic segmentation of brain structures. In this study, we examined the accuracy and consistency of those two automated protocols relative to manual segmentation, commonly considered as the gold standard technique, for estimating hippocampus and amygdala volumes in a sample of preadolescent children aged between 6 to 11 years. The volumes obtained with FreeSurfer and FSL-FIRST were evaluated and compared with manual segmentations with respect to volume difference, spatial agreement and between- and within-method correlations. Results highlighted a tendency for both automated techniques to overestimate hippocampus and amygdala volumes, in comparison to manual segmentation. This was more pronounced when using FreeSurfer than FSL-FIRST and, for both techniques, the overestimation was more marked for the amygdala than the hippocampus. Pearson correlations support moderate associations between manual tracing and FreeSurfer for hippocampus (right r=0.69, p<0.001; left r=0.77, p<0.001) and amygdala (right r=0.61, p<0.001; left r=0.67, p<0.001) volumes. Correlation coefficients between manual segmentation and FSL-FIRST were statistically significant (right hippocampus r=0.59, p<0.001; left hippocampus r=0.51, p<0.001; right amygdala r=0.35, p<0.001; left amygdala r=0.31, p<0.001) but were significantly weaker, for all investigated structures. When computing intraclass correlation coefficients between manual tracing and automatic segmentation, all comparisons, except for left hippocampus volume estimated with FreeSurfer, failed to reach 0.70. When looking at each method separately, correlations between left and right hemispheric volumes showed strong associations between bilateral hippocampus and bilateral amygdala volumes when assessed using manual segmentation or FreeSurfer. These correlations were significantly weaker when volumes were assessed with FSL-FIRST. Finally, Bland-Altman plots suggest that the difference between manual and automatic segmentation might be influenced by the volume of the structure, because smaller volumes were associated with larger volume differences between techniques. These results demonstrate that, at least in a pediatric population, the agreement between amygdala and hippocampus volumes obtained with automated FSL-FIRST and FreeSurfer protocols and those obtained with manual segmentation is not strong. Visual inspection by an informed individual and, if necessary, manual correction of automated segmentation outputs are important to ensure validity of volumetric results and interpretation of related findings.

Conceptual endophentoypes: A strategy to advance the impact of psychoneuroendocrinology in precision medicine

Psychobiological research has generated a tremendous amount of findings on the psychological, neuroendocrine, molecular and environmental processes that are directly relevant for mental and physical health, but have overwhelmed our capacity to meaningfully absorb, integrate, and utilize this knowledge base. Here, we reflect about suitable strategies to improve the translational success of psychoneuroendocrinological research in the era of precision medicine. Following a strategy advocated by the National Research Council and the tradition of endophenotype-based research, we advance here a new approach, termed conceptual endophenotypes. We define the contextual and formal criteria of conceptual endophenotypes, outline criteria for filtering and selecting information, and describe how conceptual endophenotypes can be validated and implemented at the bedside. As proof-of-concept, we describe some of our findings from research that has adopted this approach in the context of stress-related disorders. We argue that conceptual endophenotypes engineer a bridge between the bench and the bedside. This approach readily lends itself to being continuously developed and implemented. Recent methodological advances, including digital phenotyping, machine learning, grassroots collaboration, and a learning healthcare system, may accelerate the development and implementation of this conceptual endophenotype approach.

Impact of self-esteem and sex on stress reactions

Positive self-evaluation is a major psychological resource modulating stress coping behavior. Sex differences have been reported in self-esteem as well as stress reactions, but so far their interactions have not been investigated. Therefore, we investigated sex-specific associations of self-esteem and stress reaction on behavioral, hormonal and neural levels. We applied a commonly used fMRI-stress task in 80 healthy participants. Men compared to women showed higher activation during stress in hippocampus, precuneus, superior temporal gyrus (STG) and insula. Furthermore, men outperformed women in the stress task and had higher cortisol and testosterone levels than women after stress. Self-esteem had an impact on precuneus, insula and STG activation during stress across the whole group. During stress, men recruit regions associated with emotion and stress regulation, self-referential processing and cognitive control more strongly than women. Self-esteem affects stress processing, however in a sex-independent fashion: participants with lower self-esteem show higher activation of regions involved in emotion and stress regulation, self-referential processing and cognitive control. Taken together, our data suggest that men are more engaged during the applied stress task. Across women and men, lower self-esteem increases the effort in emotion and stress processing and cognitive control, possibly leading to self-related thoughts in stressful situations.

Mindfulness-based resilience training to reduce health risk, stress reactivity, and aggression among law enforcement officers : a feasibility and preliminary efficacy trial

The primary objective of this study was to assess feasibility and gather preliminary outcome data on Mindfulness-Based Resilience Training (MBRT) for law enforcement officers. Participants (nu202f=u202f61) were randomized to either an 8-week MBRT course or a no intervention control group. Self-report and physiological data were collected at baseline, post-training, and three months following intervention completion. Attendance, adherence, post-training participant feedback, and interventionist fidelity to protocol all demonstrated feasibility of MBRT for law enforcement officers. Compared to no intervention controls, MBRT participants experienced greater reductions in salivary cortisol, self-reported aggression, organizational stress, burnout, sleep disturbance, and reported increases in psychological flexibility and non-reactivity at post-training; however, group differences were not maintained at three-month follow-up. This initial randomized trial suggests MBRT is a feasible intervention. Outcome data suggest MBRT targets key physiological, psychological, and health risk factors in law enforcement officers, consistent with the potential to improve officer health and public safety. However, follow-up training or booster sessions may be needed to maintain training gains. A fully powered longitudinal randomized trial is warranted.

The dynamic interplay between acute psychosocial stress, emotion and autobiographical memory

Although acute psychosocial stress can impact autobiographical memory retrieval, the nature of this effect is not entirely clear. One reason for this ambiguity is because stress can have opposing effects on the different stages of autobiographical memory retrieval. We addressed this issue by testing how acute stress affects three stages of the autobiographical memory retrieval – accessing, recollecting and reconsolidating a memory. We also investigate the influence of emotion valence on this effect. In a between-subjects design, participants were first exposed to an acute psychosocial stressor or a control task. Next, the participants were shown positive, negative or neutral retrieval cues and asked to access and describe autobiographical memories. After a three to four day delay, participants returned for a second session in which they described these autobiographical memories. During initial retrieval, stressed participants were slower to access memories than were control participants; moreover, cortisol levels were positively associated with response times to access positively-cued memories. There were no effects of stress on the amount of details used to describe memories during initial retrieval, but stress did influence memory detail during session two. During session two, stressed participants recovered significantly more details, particularly emotional ones, from the remembered events than control participants. Our results indicate that the presence of stress impairs the ability to access consolidated autobiographical memories; moreover, although stress has no effect on memory recollection, stress alters how recollected experiences are reconsolidated back into memory traces.

Sexual orientation moderates the association between parental overprotection and stress biomarker profiles

ABSTRACT Early experiences with parents may be particularly difficult for lesbian, gay and bisexual (LGB) individuals who face stigma that is linked to potentially distinct stress-related biobehavioural profiles. This study examined the association between parental bonding in relation to acute stress (cortisol reactivity) and chronic stress (allostatic load) in LGB and heterosexual individuals. The sample consisted of 87 healthy adults (mean [SD] age = 24.6 [0.6] years; LGB: n = 46, 43% women; and heterosexual n = 41, 49% women). Regressions tested the main effects of retrospectively assessed parental overprotection and care before the age of 16 on stress reactive cortisol (area under the curve) and allostatic load (indexed using 21 neuroendocrine, immune, metabolic and cardiovascular biomarkers), and whether sexual orientation status moderated this association. Results revealed that parental overprotection was associated with increased cortisol reactivity only for LGB participants, but not for heterosexual participants. By contrast, parental overprotection was associated with higher allostatic load only for heterosexual participants, but not for LGB participants. While the functional significance of this requires further study, these preliminary findings suggest that adaptive processes among LGB individuals may mitigate the negative effects of parental overprotection on markers of chronic stress.

Corrigendum to “Hippocampus and amygdala volumes from magnetic resonance images in children: Assessing accuracy of FreeSurfer and FSL against manual segmentation”[NeuroImage 129 (2016) 1–14]

Author(s): Schoemaker, Dorothee; Buss, Claudia; Head, Kevin; Sandman, Curt A; Davis, Elysia P; Chakravarty, M Mallar; Gauthier, Serge; Pruessner, Jens C

The EADC-ADNI harmonized protocol for hippocampal segmentation: A validation study

ABSTRACT Recently, a group of major international experts have completed a comprehensive effort to efficiently define a harmonized protocol for manual hippocampal segmentation that is optimized for Alzheimers research (known as the EADC‐ADNI Harmonized Protocol (the HarP)). This study compares the HarP with one of the widely used hippocampal segmentation protocols (Pruessner, 2000), based on a single automatic segmentation method trained separately with libraries made from each manual segmentation protocol. The automatic segmentation conformity with the corresponding manual segmentation and the ability to capture Alzheimers disease related hippocampal atrophy on large datasets are measured to compare the manual protocols. In addition to the possibility of harmonizing different procedures of hippocampal segmentation, our results show that using the HarP, the automatic segmentation conformity with manual segmentation is also preserved (Dices Symbol for Pruessner and HarP respectively (p=0.726 for common training library)). Furthermore, the results show that the HarP can capture the Alzheimers disease related hippocampal volume differences in large datasets. The HarP‐derived segmentation shows large effect size (Cohens d = 1.5883) in separating Alzheimers Disease patients versus normal controls (AD:NC) and medium effect size (Cohens d = 0.5747) in separating stable versus progressive Mild Cognitively Impaired patients (sMCI:pMCI). Furthermore, the area under the ROC curve for a LDA classifier trained based on age, sex and HarP‐derived hippocampal volume is 0.8858 for AD:NC, and for 0.6677 sMCI:pMCI. These results show that the harmonized protocol‐derived labels can be widely used in clinic and research, as a sensitive and accurate way of delineating the hippocampus. Symbol. No caption available.

Endurance- and Resistance-Trained Men Exhibit Lower Cardiovascular Responses to Psychosocial Stress Than Untrained Men

Evidence shows that regular physical exercise reduces physiological reactivity to psychosocial stress. However, previous research mainly focused on the effect of endurance exercise, with only a few studies looking at the effect of resistance exercise. The current study tested whether individuals who regularly participate in either endurance or resistance training differ from untrained individuals in adrenal and cardiovascular reactivity to psychosocial stress. Twelve endurance-trained men, 10 resistance-trained men, and 12 healthy but untrained men were exposed to a standardized psychosocial stressor, the Trier Social Stress Test. Measurements of heart rate, free salivary cortisol levels, and mood were obtained throughout the test and compared among the three groups. Overall, both endurance- and resistance-trained men had lower heart rate levels than untrained men, indicating higher cardiac performance of the trained groups. Trained men also exhibited lower heart rate responses to psychosocial stress compared with untrained men. There were no significant group differences in either cortisol responses or mood responses to the stressor. The heart rate results are consistent with previous studies indicating reduced cardiovascular reactivity to psychosocial stress in trained individuals. These findings suggest that long-term endurance and resistance trainings may be related to the same cardiovascular benefits, without exhibiting strong effects on the cortisol reactivity to stress.

Neurobiological Correlates and Predictors of Two Distinct Personality Trait Pathways to Escalated Alcohol Use

Background The delineation of the behavioral neurobiological mechanisms underlying the heterogeneous pathways for alcohol use disorders (AUDs) is ostensibly imperative for the development of more cost-effective treatments predicated on better understanding of this complex psychopathology. Methods 1) Forty-eight high anxiety sensitive (HAS) and high sensation seeking (HSS) psychopathology-free emerging adults (mean (SD) age: 20.4 (1.9) years) completed a Face Emotion Processing Task and a social stress paradigm (Montreal Imaging Stress Task) during functional magnetic resonance imaging sessions with and without alcohol ingestion (1 ml/kg of 95% USP alcohol, p.o.). Drug and alcohol use was reassessed during follow-up interviews 2–3 years later. Outcomes The effects of alcohol (versus placebo) ingestion depended upon the task and risk group. In response to negative (versus neutral) faces, alcohol diminished amygdala (AMYG) activations in HAS but not HSS subjects. In response to psychosocial evaluative stress, alcohol enhanced activations of the medial orbitofrontal cortex (mOFC), perigenual anterior cingulate cortex, and nucleus accumbens in HAS male subjects (HASMS), but decreased mOFC activity in HSS male subjects (HSSMS). At follow-up, a greater alcohol versus placebo differential for threat-related AMYG activations predicted escalating drinking and/or illicit drug use among HAS but not HSS participants, whereas a greater differential for mOFC activations during acute social stress predicted escalating substance use among HSS but not HAS participants. Interpretation This double dissociation provides evidence of distinct neurobiological profiles in a priori identified personality trait-based risk groups for AUDs, and links these signatures to clinically relevant substance use outcomes at follow-up. AUD subtypes might benefit from motivationally and personality-specific ameliorative and preventative interventions.