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INTRODUCTION: Research on stress-related disorders and brain imaging suggests that (acute) stress might impact the capacity to mentally simulate specific episodic future events (EFT) through the effects of cortisol on brain regions supporting this cognitive function, such as the prefrontal cortices. This study aims to examine the mechanisms underlying this link, using transcranial Direct Current Stimulation (tDCS) over the left dorsolateral prefrontal cortex. METHODS: 60 healthy participants were subjected to the Montreal Imaging Stress Task (MIST), followed by either active or sham tDCS. After stimulation, the EFT task was administered. Salivary cortisol was measured throughout the protocol. RESULTS: Higher cortisol AUCi values were linked to less specific episodic future thoughts. Moreover, active tDCS enhanced EFT specificity irrespective of cortisol, especially in high trait ruminators. We did not observe an effect from active tDCS on cortisol AUCi, and equally there was no interaction effect between cortisol AUCi and stimulation condition predictive for EFT specificity. CONCLUSION: Although we did not find evidence for the effects of tDCS on the HPA-system, our data reveal a crucial link between two critical predictors of mental health for the first time, and provide a solution to help rehabilitate EFT deficits.Trial registration: Netherlands National Trial Register identifier: ntr004..

The tendency to ruminate (i.e., repetitive, self-referential, negative thoughts) is a maladaptive form of emotional regulation and represents a transdiagnostic vulnerability factor for stress-related psychopathology. Vagally-mediated heart rate variability (HRV), reflecting parasympathetic nervous system activity, is commonly used as a physiological marker of stress regulation. Past research has suggested a link between trait rumination and resting HRV at baseline; however, inconsistent results exist in healthy individuals. In this study, we investigated the association between the tendency to ruminate and resting HRV measured at baseline in a healthy population using a large cross-sectional dataset (N = 1189, 88% women; mean age = 21.55, ranging from 17 to 48 years old), which was obtained by combining samples of healthy individuals from different studies from our laboratory. The results showed no cross-sectional correlation between resting baseline HRV and trait rumination (confirmed by Bayesian analyses), even after controlling for important confounders such as gender, age, and depressive symptoms. Also, a nonlinear relationship was rejected. In summary, based on our results in a large sample of healthy individuals, baseline resting HRV is not a trait marker of the tendency to ruminate.

There is a growing interest in applying double-dose repetitive transcranial Magnetic Stimulation (rTMS) as a therapeutic tool for stress-related psychiatric disorders. Such stimulation protocols may shorten the treatment duration and may result in faster symptom improvement. Currently, theta-burst stimulation (TBS) protocols have gained attention because of their significantly reduced treatment duration, compared to conventional rTMS. However, the effect of one or twice daily rTMS sessions remains unclear in relation to stress. Using a two-period cross-over design, we examined the impact of double-dosed intermittent (TBS) over the left dorsolateral prefrontal cortex on stress responses (salivary cortisol) in thirty-eight healthy participants after being stressed by a validated psychosocial stress task: the Trier Social Stress Test. After the first active iTBS session, as contrasted to sham, no differential effects on salivary output were observed. However, after the second active session, there was a significantly smaller decrease of salivary cortisol concentrations in the active iTBS condition compared to sham. Our results suggest that double-dosed iTBS after being stressed might differently affect stress recovery compared to a single session of iTBS.

Transcranial Direct Current Stimulation (tDCS) is an effective treatment during the acute phase of a major depressive episode (MDE), although the evidence for its follow-up efficacy is mixed. A systematic review and meta-analysis were performed. MEDLINE/PubMed, Scopus (EMBASE), Web of Science, Cochrane Library and additional sources were searched from inception to April 29, 2021. Studies that followed up adults treated with tDCS during an MDE - using (interventional) and/or not using (observational) tDCS in the follow-up period were included. The primary outcome was the Hedges' g for the follow-up depression scores. Small study effects and sources of heterogeneity were explored. 427 studies were retrieved and 11 trials (13 datasets, n = 311) were included, most presenting moderate bias. Results showed a follow-up depression improvement (k = 13, g = -0.81, 95% confidence interval [CI]: -1.28; -0.34, I² = 84.0%), which was probably driven by the interventional studies (k = 7, g= -1.12, 95% CI: -1.84; -0.40, I² = 87.1%). No predictor of response was associated with the outcome. No risk of publication bias was found. Significant between-study heterogeneity may have influenced the overall results. Our findings suggest that tDCS produces effects beyond the intervention period during MDEs. Maintenance sessions are advised in future research.

Background Randomised clinical trials (RCTs) investigating transcranial direct current stimulation (tDCS) efficacy for depression show significant heterogeneity in outcomes. Objective To investigate the magnitude of the sham tDCS response and its potential moderators in the treatment of depression. Methodology A systematic review and aggregate meta-analysis (PROSPERO ID CRD42020161254). The systematic review was conducted in the PubMed, Scopus (EMBASE) and Cochrane Library databases. Only RCTs enrolling adult subjects with an acute depressive episode with a sham tDCS group were included. Results Twenty-three studies (twenty-five datasets, 501 participants) were included. Sham tDCS response was large (Hedges' g = 1.09; 95% CI: 0.8;1.38). Secondary and subgroup analyses showed that sham protocols employing a ramp-up/ramp-down at the beginning and end of stimulation presented a significantly lower sham response compared to other protocols. Univariate meta-regression analyses found that sham response was associated with higher risk of blinding bias, and with thetreatment effect size of the active tDCS group. Subgroup analyses also showed that placement of the cathode over the lateral right frontal area (F8) presented a significantly lower sham response. Other moderators, including treatment resistance, baseline severity of depressive symptoms, and total charge delivered were not associated with the magnitude of the sham response. Conclusion The sham tDCS response was large. Our findings demonstrate the need for standardization of sham tDCS protocols and bring attention to important considerations that can guide future RCTs employing tDCS for the treatment of MDD.

The prefrontal cortex, and especially the Dorsolateral Prefrontal Cortex (DLPFC), plays an inhibitory role in the regulation of the Hypothalamic-Pituitary-Adrenal (HPA) axis under stressful situations. Moreover, recent evidence suggests that a sustained DLPFC activation is associated with adaptive stress regulation in anticipation of a stressful event, leading to a reduced stress-induced amygdala response, and facilitating the confrontation with the stressor. However, studies using experimental manipulation of the activity of the DLPFC before a stressor are scarce, and more research is needed to understand the specific role of this brain area in the stress-induced physiological response. This pre-registered study investigated the effect on stress regulation of a single excitatory high frequency (versus sham) repetitive transcranial magnetic stimulation (HF-rTMS) session over the left DLPFC applied before the Trier Social Stress Test in 75 healthy young women (M = 21.05, SD = 2.60). Heart rate variability (HRV) and salivary cortisol were assessed throughout the experimental protocol. The active HF-rTMS and the sham group showed a similar cognitive appraisal of the stress task. No differences in HRV were observed during both the anticipation and the actual confrontation with the stress task and therefore, our results did not reflect DLPFC-related adaptive anticipatory adjustments. Importantly, participants in the active HF-rTMS group showed a lower cortisol response to stress. The effect of left prefrontal HF-rTMS on the stress system provides further critical experimental evidence for the inhibitory role played by the DLPFC in the regulation of the HPA axis.

Plant survival under abiotic stress conditions requires morphological and physiological adaptations. Adverse soil conditions directly affect root development, although the underlying mechanisms remain largely to be discovered. Plant hormones regulate normal root growth and mediate root morphological responses to abiotic stress. Hormone synthesis, signal transduction, perception and cross-talk create a complex network in which metal stress can interfere, resulting in root growth alterations. We focus on Arabidopsis thaliana, for which gene networks in root development have been intensively studied, and supply essential terminology of anatomy and growth of roots. Knowledge of gene networks, mechanisms and interactions related to the role of plant hormones is reviewed. Most knowledge has been generated for auxin, the best-studied hormone with a pronounced primary role in root development. Furthermore, cytokinins, gibberellins, abscisic acid, ethylene, jasmonic acid, strigolactones, brassinosteroids and salicylic acid are discussed. Interactions between hormones that are of potential importance for root growth are described. This creates a framework that can be used for investigating the impact of abiotic stress factors on molecular mechanisms related to plant hormones, with the limited knowledge of the effects of the metals cadmium, copper and zinc on plant hormones and root development included as case example.