Chronic stress and executive functioning: A specification-curve analysis.

To investigate the association between chronic stress and executive functioning (EF), we assessed 514 young to middle-aged adults in three EF tasks (i.e., Number-Letter, 2-Back, Go/Nogo) that assessed shifting, updating, and inhibition. Chronic stress was assessed by various self-report measures and hair cortisol concentrations as indicators of subjective and objective chronic stress, respectively. In order to test the association between chronic stress and EF, we fit a structural equation model with a latent common EF factor predicted by subjective and objective chronic stress on Kaplan-Meier estimates of response times. Controlling for participants' sex, age household income and the delay between cognitive testing and hair sample collection, neither subjective nor objective chronic stress showed a meaningful association with common EF. Exploratory analyses suggested a moderation effect of income on the association between subjective chronic stress and common EF, with a smaller association for high-income participants. Additionally, we conducted a specification-curve analysis on the association between chronic stress and EF to assess the influence of different analysis choices on results in our dataset. This analysis confirmed the absence of a coherent association between chronic stress and EF by showing that the majority of analytical choices produced null effects and only a small number of analytical choices produced meaningful associations (negative or positive). Taken together, our findings suggest that common EF likely remains preserved under the influence of chronic stress. Our specification-curve analysis, however, also shows that chronic stress may also have either a positive or a negative effect on EF, depending on the choice of covariates and measures of chronic stress and EF. Consequently, more research on the role of these factors for the association between chronic stress and EF is needed to avoid the interpretation of non-replicable stress-EF associations caused by analytical choices or selection bias.

Cortisol secretion predicts functional macro-scale connectivity of the visual cortex: A data-driven Multivoxel Pattern Analysis (MVPA).

BACKGROUND: Functional connectivity is a fundamental principle of brain organization. Cortisol, the end product of the hypothalamic-pituitary-adrenal axis, is a potent modulator of brain functions. Previous studies investigating the association between cortisol levels on brain connectivity are, however, limited to specifica priori defined brain networks. Such hypothesis-driven approaches only partly capture the full extent of spatial modulatory effects that cortisol exerts on brain connectivity. Consequently, the aim of this study was a data-driven identification of brain regions where connectivity patterns covary significantly with cortisol levels. METHODS: Eighty-eight healthy right-handed individuals participated in a task-independent fMRI-resting-state functional connectivity (rsFC) measurement. The cortisol concentrations in saliva were measured at eight points in time around the resting state measurement. Using a multi-voxel pattern analysis (MVPA), seed regions were identified whose activity covaried strongest with cortisol levels. Seed-to-voxel analyses were then performed to isolate corresponding networks affected by cortisol variation. RESULTS: The MVPA identified three regions in the primary and secondary visual cortex where connectivity patterns were associated with cortisol secretion. Seed-to-voxel analysis revealed large lateral connectivity clusters that mainly correspond to the salience and control network, but also to auditory and pericentral regions. Subsequent dose-response analysis suggests that cortisol levels below ∼10 nmol/L weakly influenced connectivity between the identified regions. DISCUSSION: The results indicate a dose-dependent association between cortisol levels and the rsFC of the visual cortex to several lateral brain regions associated with perception, attention, cognition, salience mapping and motor actions. It is possible that the effects of cortisol on cognitive functions may be (at least partially) mediated by cortisol effects on the underlying sensory processes.

The psychometric properties and temporal dynamics of subjective stress, retrospectively assessed by different informants and questionnaires, and hair cortisol concentrations.

To date, there is only scarce evidence for a considerable association of subjective and objective stress measures, which might be attributable to method bias (e.g., confounding) and/or asynchrony of their temporal changes. To validate different subjective stress measures by a physiological measure of long-term stress (hair cortisol concentrations; HCC), 37 heterosexual couples (N = 74) completed a 12-week internet-based assessment protocol comprised of a weekly hassle scale (WHS; once per week), a perceived stress scale (PSS; once per month), and a chronic stress scale (TICS; once after three months). Partners provided vicarious stress ratings. When averaged across time, self-reported WHS significantly predicted HCC (r = 0.27), whereas the PSS and TICS did not (r < 0.22). Dynamic factor analysis (i.e., state-space modelling) confirmed that WHS was the most valid indicator of subjective stress, explaining up to 16% of the variance in HCC (r = 0.37) with a time lag of ~4 weeks. This temporally delayed effect of subjective stress is consistent with the presumed retrospective character of HCC, but also suggests that the majority of variance in hair cortisol is attributable to other causes than subjective stress such as individual disposition to display increased adrenocortical activity.

How to disentangle psychobiological stress reactivity and recovery: A comparison of model-based and non-compartmental analyses of cortisol concentrations.

This article seeks to address the prevailing issue of how to measure specific process components of psychobiological stress responses. Particularly the change of cortisol secretion due to stress exposure has been discussed as an endophenotype of many psychosomatic health outcomes. To assess its process components, a large variety of non-compartmental parameters (i.e., composite measures of substance concentrations at different points in time) like the area under the concentration-time curve (AUC) are commonly utilized. However, a systematic evaluation and validation of these parameters based on a physiologically plausible model of cortisol secretion has not been performed so far. Thus, a population pharmacokinetic (mixed-effects stochastic differential equation) model was developed and fitted to densely sampled salivary cortisol data of 10 males from Montreal, Canada, and sparsely sampled data of 200 mixed-sex participants from Dresden, Germany, who completed the Trier Social Stress Test (TSST). Besides the two major process components representing (1) stress-related cortisol secretion (reactivity) and (2) cortisol elimination (recovery), the model incorporates two additional, often disregarded components: (3) the secretory delay after stress onset, and (4) deviations from the projected steady-state concentration due to stress-unrelated fluctuations of cortisol secretion. The fitted model (R2 = 99%) was thereafter used to investigate the correlation structure of the four individually varying, and readily interpretable model parameters and eleven popular non-compartmental parameters. Based on these analyses, we recommend to use the minimum-maximum cortisol difference and the minimum concentration as proxy measures of reactivity and recovery, respectively. Finally, statistical power analyses of the reactivity-related sex effect illustrate the consequences of using impure non-compartmental measures of the different process components that underlie the cortisol stress response.

NMDA receptor modulation by dextromethorphan and acute stress selectively alters electroencephalographic indicators of partial report processing.

Proceeding from a biophysical network model, the present study hypothesized that glutamatergic neurotransmission across the NMDA receptor (NMDAR) plays a key role in visual perception and its modulation by acute stress. To investigate these hypotheses, behavioral and electroencephalographic (EEG) indicators of partial report task processing were assessed in twenty-four healthy young men who randomly received a non-competitive NMDAR antagonist (0.8 mg/kg dextromethorphan, DXM) or a placebo, and concurrently accomplished a stress-induction (MAST) or control protocol in three consecutive sessions. Saliva samples served to quantify cortisol responses to the MAST, whereas a passive auditory oddball paradigm was implemented to verify the impact of DXM on the EEG-derived mismatch negativity component (MMN). DXM administration significantly increased MMN amplitudes but not salivary cortisol concentrations. By contrast, concurrent MAST exposure significantly reduced MMN latencies but also increased cortisol concentrations. With regard to EEG indicators, DXM administration reduced visually "evoked" (30Hz to 50Hz) and "induced" occipital gamma-band activity (70Hz to 100Hz), which was partly compensated by additional MAST exposure. However, neither the interventions nor EEG activity were significantly associated with behavioral partial report sensitivities. In summary, the present data suggest that glutamatergic neurotransmission across the NMDAR is only one among many determinants of intact visual perception. Accordingly, therapeutic doses of DXM and their inhibitory modulation by stress probably yield more pronounced electroencephalographic as compared with behavioural effects.

Hydrocortisone Counteracts Adverse Stress Effects on Dual-Task Performance by Improving Visual Sensory Processes.

The impact of acute stress on executive processes is commonly attributed to glucocorticoid-induced disruptions of the pFC. However, the occipital cortex seems to express a higher density of glucocorticoid receptors. Consequently, acute stress effects on executive processes could as well be mediated by glucocorticoid (e.g., cortisol)-induced alterations of visual sensory processes. To investigate this alternative route of stress action by demarcating the effects of acute stress and cortisol on executive from those on visual sensory processes, 40 healthy young men completed a standardized stress induction (i.e., the Trier Social Stress Test) and control protocol in two consecutive sessions. In addition, they received either a placebo or hydrocortisone (0.12-mg/kg bodyweight) pill and processed a dual and a partial report task to assess their executive and visual sensory processing abilities, respectively. Hydrocortisone administration improved both partial report and dual-task performance as indicated by increased response accuracies and/or decreased RTs. Intriguingly, the hydrocortisone-induced increase in dual-task performance was completely mediated by its impact on partial report performance (i.e., visual sensory processes). Moreover, RT measures in both tasks shared approximately 26% of variance, which was only in part attributable to hydrocortisone administration (ΔR2 = 8%). By contrast, acute stress selectively impaired dual-task performance (i.e., executive processes), presumably through an alternative route of action. In summary, the present results suggest that cortisol secretion (as mimicked by hydrocortisone administration) may counteract adverse residual stress effects on executive processes by improving visual sensory processes (e.g., the maintenance and amplification of task-relevant sensory information).

Hydrocortisone accelerates the decay of iconic memory traces: on the modulation of executive and stimulus-driven constituents of sensory information maintenance.

A substantial amount of research documents the impact of glucocorticoids on higher-order cognitive functioning. By contrast, surprisingly little is known about the susceptibility of basic sensory processes to glucocorticoid exposure given that the glucocorticoid receptor density in the human visual cortex exceeds those observed in prefrontal and most hippocampal brain regions. As executive tasks also rely on these sensory processes, the present study investigates the impact of glucocorticoid exposure on different performance parameters characterizing the maintenance and transfer of sensory information from iconic memory (IM; the sensory buffer of the visual system) to working memory (WM). Using a crossover factorial design, we administered one out of three doses of hydrocortisone (0.06, 0.12, or 0.24mg/kg bodyweight) and a placebo to 18 healthy young men. Thereafter participants performed a partial report task, which was used to assess their individual ability to process sensory information. Blood samples were concurrently drawn to determine free and total cortisol concentrations. The compiled pharmacokinetic and psychophysical data demonstrates that free cortisol specifically accelerated the decay of sensory information (r=0.46) without significantly affecting the selective information transfer from IM to WM or the capacity limit of WM. Specifically, nonparametric regression revealed a sigmoid dose-response relationship between free cortisol levels during the testing period and the IM decay rates. Our findings highlight that glucocorticoid exposure may not only impact on the recruitment of top-down control for an active maintenance of sensory information, but alter their passive (stimulus-driven) maintenance thereby changing the availability of information prior to subsequent executive processing.

Do venepuncture procedures induce cortisol responses? A review, study, and synthesis for stress research.

Venepuncture procedures are frequently employed to continuously monitor humoral stress markers. As such procedures are conceived as "potent psychological and physiological stressors", there is a need to determine whether venepuncture procedures themselves elicit cortisol responses and if so, how to deal with them appropriately. In order to assess the rate of cortisol responses to venepuncture, we conducted a literature review, which suggested that venepuncture procedures induce cortisol responses with a probability of approximately 30%. By utilizing Bayesian analysis, this result was integrated with the cortisol data of 18 healthy men who were exposed to a venepuncture procedure twice (time lag: 1 week). The currently observed response rate of 47% differed substantially from the earlier findings, which we attribute to a self-selective sampling of participants. In addition, participants showing a response to the first venepuncture were highly likely to also show a response to the second one. In this regard, we discuss the presumed conditioning of cortisol responses to venepuncture procedures. To prevent the superposition of venepuncture-induced cortisol responses and responses induced by target stressors, we propose a time- and selection-based strategy: cortisol samples taken about 110min after venepuncture should be virtually adjusted for its superimposing effects. Furthermore, previous experiences of venepuncture were highly predictive for cortisol responsiveness. This association could be utilized in further studies to identify participants who will probably show a cortisol response to venepuncture.