Stress priming transcranial direct current stimulation (tDCS) enhances updating of emotional content in working memory.

Transcranial direct current stimulation (tDCS) targeting the prefrontal cortex has emerged as a valuable tool in psychiatric research. Understanding the impact of affective states, such as stress at the time of stimulation, on the efficacy of prefrontal tDCS is crucial for advancing tDCS interventions. Stress-primed tDCS, wherein stress is used as a priming agent, has the potential to modulate neural plasticity and enhance cognitive functions, particularly in emotional working memory. However, prior research using stress-primed tDCS focused solely on non-emotional working memory performance, yielding mixed results. In this sham-controlled study, we addressed this gap by investigating the effects of stress-primed bifrontal tDCS (active versus sham) on both non-emotional and emotional working memory performance. The study was conducted in 146 healthy individuals who were randomly assigned to four experimental groups. The Trier Social Stress Test (TSST) or a control variant of the test was used to induce a stress versus control state. The results showed that stress priming significantly enhanced the effects of tDCS on the updating of emotional content in working memory, as evidenced by improved accuracy. Notably, no significant effects of stress priming were found for non-emotional working memory performance. These findings highlight the importance of an individual's prior affective state in shaping their response to tDCS, especially in the context of emotional working memory.

Dose-dependent response of prefrontal transcranial direct current stimulation on the heart rate variability: An electric field modeling study.

Transcranial direct current stimulation (tDCS) of the prefrontal cortex (PFC) modulates the autonomic nervous system by activating deeper brain areas via top-down pathway. However, effects on the nervous system are heterogeneous and may depend on the amount of current that penetrates. Therefore, we aimed to investigate the variable effects of tDCS on heart rate variability (HRV), a measure of the functional state of the autonomic nervous system. Using three prefrontal tDCS protocols (1.5, 3 mA and sham), we associated the simulated individual electric field (E-field) magnitude in brain regions of interest with the HRV effects. This was a randomized, double-blinded, sham-controlled and within-subject trial, in which healthy young-adult participants received tDCS sessions separated by 2 weeks. The brain regions of interest were the dorsolateral PFC (DLPFC), anterior cingulate cortex, insula and amygdala. Overall, 37 participants were investigated, corresponding to a total of 111 tDCS sessions. The findings suggested that HRV, measured by root mean squared of successive differences (RMSSD) and high-frequency HRV (HF-HRV), were significantly increased by the 3.0 mA tDCS when compared to sham and 1.5 mA. No difference was found between sham and 1.5 mA. E-field analysis showed that all brain regions of interest were associated with the HRV outcomes. However, this significance was associated with the protocol intensity, rather than inter-individual brain structural variability. To conclude, our results suggest a dose-dependent effect of tDCS for HRV. Therefore, further research is warranted to investigate the optimal current dose to modulate HRV.

Trait-dependent effects of theta burst stimulation after psychosocial stress: a sham-controlled study in healthy individuals.

OBJECTIVE: Previous studies suggest that theta burst stimulation (TBS), a form of repetitive transcranial magnetic stimulation (rTMS), applied to the left dorsolateral prefrontal cortex (DLPFC) might be a promising approach to modulate stress-reactive rumination and the associated psychophysiological stress response. Crucially, individuals showing higher levels of trait rumination might benefit more from prefrontal stimulation. METHODS: In this sham-controlled study, 127 healthy individuals, with varying ruminative tendencies, received a single-session of intermittent TBS (iTBS), continuous TBS (cTBS) or sham TBS (sTBS) over the left DLPFC before being confronted with a Trier Social Stress Test. RESULTS: Results showed significant TBS effects on salivary cortisol as a function of trait rumination. cTBS, as compared to sTBS and iTBS, resulted in an attenuated stress-induced cortisol response in high compared to low trait ruminators. Although independent of trait rumination levels, cTBS showed positive effects on stress-related changes in mood and, both cTBS and iTBS (versus sham) presented an enhanced heart rate recovery following the stressor. We found no evidence for (trait rumination-dependent) TBS effects on stress-reactive rumination, negative affect, subjective stress or heart rate variability. CONCLUSIONS: cTBS shows beneficial effects on certain measures of stress, especially in high trait ruminators. SIGNIFICANCE: These findings highlight the importance of accounting for individual differences when examining TBS effects.

Acute stress impacts reaction times in older but not in young adults in a flanker task.

Acute psychosocial stress effects on inhibition have been investigated in young adults, but little is known about these effects in older adults. The present study investigated effects of the Trier Social Stress Test on cognitive inhibition (i.e., ability to ignore distracting information) using a cross-over (stress vs. control) design in healthy young (N = 50; 18-30 years; Mage = 23.06) versus older adults (N = 50; 65-84 years; Mage = 71.12). Cognitive inhibition was measured by a letter flanker task and psychophysiological measures (cortisol, heart rate, subjective stress) validated the stress induction. The results showed that while stress impaired overall accuracy across age groups and sessions, stress (vs. control) made older adults' faster in session 1 and slower in session 2. Given that session 2 effects were likely confounded by practice effects, these results suggest that acute psychosocial stress improved older adults' RTs on a novel flanker task but impaired RTs on a practiced flanker task. That is, the interaction between stress and learning effects might negatively affect response execution when testing older adults on flanker tasks. If confirmed by future research, these results might have important implications especially in settings where repeated cognitive testing is performed under acute stress.

Adult age differences in the psychophysiological response to acute stress.

Age-related differences in the psychophysiology of the acute stress response are poorly understood given the limited number of studies and the high heterogeneity of findings. The present study contributes by investigating age differences in both the psychological and physiological responses to acute stress in a sample of healthy younger (N = 50; 18-30; Mage = 23.06; SD = 2.90) and older adults (N = 50; 65-84; Mage = 71.12; SD = 5.02). Specifically, the effects of psychosocial stress (i.e., age-adapted Trier Social Stress Test) were investigated at numerous timepoints throughout the stress response phases (i.e., baseline, anticipation, reactivity, recovery) on cortisol, heart rate, subjective stress, and anticipatory appraisal of the stressful situation. The study was conducted in a between-subject (younger vs. older) cross-over (stress vs. control) design. Results revealed age-related differences in both physiological and psychological variables: older adults had overall lower salivary cortisol levels in the stress and control conditions and lower stress-induced cortisol increase (i.e., AUCi). In addition, older adults' cortisol reactivity was delayed compared to younger adults. Older adults showed a lower heart rate response in the stress condition while no age differences were observed in the control condition. Finally, older adults reported less subjective stress and a less negative stress appraisal during the anticipation phase than younger adults, which could potentially explain lower physiological reactivity in this age group. Results are discussed in relation to the existing literature, potential underlying mechanisms, and future directions for the field.

The effects of left dorsolateral prefrontal transcranial direct current stimulation on episodic future thinking following acute psychosocial stress.

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..

Depression and Suicide Risk in Mild Cognitive Impairment: The Role of Alzheimer's Disease Biomarkers.

BACKGROUND: Patients with depression and mild cognitive impairment (MCI) are at greater risk of developing dementia. Depression involves a higher risk of suicidal ideation (SI) and suicide attempts (SA). Biomarkers of Alzheimer's Disease (AD) could help to clarify the role of depression and SI in AD. METHOD: Fifty-nine participants aged > 50 with criteria of MCI positive (MCI-AD) (n=22) and negative (MCI-Non AD) (n=24) AD and healthy controls (HC) (n=13) were evaluated. We used the Geriatric Depression Scale (GDS-30) and the GDS-SI factor to measure depression and indirect risk for suicide, respectively. Additionally, AD biomarkers such as amyloid-ß (Aß), hyperphosphorilated tau (P-tau), and total tau (T-tau) in cerebrospinal fluid (CSF) were analyzed. RESULTS: No significant differences between the groups were found in depression. However, in the MCI-AD group, lower P-tau and T-tau levels were related to higher GDS-SI scores, suggesting that MCI-AD patients with lower AD pathology are at a higher risk of suicide. CONCLUSIONS: The result highlights the importance of considering SI in the initial phases of AD, and the potential role of AD biomarkers in early detection of symptoms.

EEG markers and subjective memory complaints in young and older people.

Subjective memory complaints (SMCs) have been related to subtle cognitive deficits and neural changes. In this study, we investigated whether EEG rhythms, usually altered in mild cognitive impairment and Alzheimer's disease, are also affected in SMCs compared to people without SMCs. Seventy-one older adults (55-74 years old) and 75 young people (18-34 years old) underwent 3 min of EEG recording in a resting-state condition with their eyes open (EO) and eyes closed (EC) and a comprehensive neuropsychological evaluation. The EEG measures included were power spectral delta (0.5-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), beta (13-30 Hz), and EEG reactivity to EO. Compared to controls, older people with SMCs showed increased theta power and a loss of alpha reactivity to EO. Additionally, in older participants with SMCs, the theta power spectral was related to deficits in verbal memory. In contrast, we failed to find differences in the young people with SMCs, compared to the control group, in the power spectral or the EEG reactivity to EO. Our findings suggest that neurophysiological markers of brain dysfunction may identify cognitive changes even before they are observed on objective neuropsychological tests, at least in older people.

Double the dose, double the impact? Effects of iTBS on salivary cortisol in stressed healthy volunteers.

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.

Pre-pandemic Psychobiological Features Predict Impact of COVID-19 Confinement on Loneliness.

The coronavirus disease 2019 (COVID-19) pandemic led to various government-imposed limitations on social interaction and strict home confinement. Such involuntary social-distancing policies can exacerbate feelings of loneliness and alter emotional well-being. Dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) axis is a potential mechanism for loneliness' deleterious health effects. In this study, we explored whether pre-pandemic diurnal cortisol output (AUC G ), a measure of HPA axis function, may predict the propensity to changes in loneliness during long-term COVID-19 home confinement and if extraversion would moderate this relationship. This association has been explored by analysing the impact of COVID-19 pandemic and strict home confinement on social and emotional loneliness in 45 Spanish young adults. Diurnal cortisol levels were measured from five saliva samples obtained across a day just before the pandemic, and data about participants' perceived loneliness, empathic state, extraversion, and prospective volunteering were obtained both before and during the confinement. Participants' social and family loneliness increased during long-term strict home confinement, while prospective volunteering tendencies and extraversion decreased. Importantly, after adjusting for relevant confounders, moderation analyses revealed that in young adults with high pre-pandemic extraversion, a higher AUC G predicted a larger increase in social loneliness during confinement, while in individuals with low extraversion, AUC G was negatively related to change in loneliness. Our findings highlight the utility of pre-pandemic diurnal cortisol output in predicting the social impact of COVID-19 home confinement, presenting this hormone as a potential biomarker for a priori identification of at-risk groups during public health crises.

Optimism as a protective factor against the psychological impact of COVID-19 pandemic through its effects on perceived stress and infection stress anticipation.

The 2019 coronavirus disease (COVID-19) and the recommended social isolation presented a challenge to people's mental health status. Optimism is a psychological factor that plays a key role in the evaluation of stressful situations. The purpose of this study was to investigate the mediating role of perceived stress and Covid-19-related stress anticipation in the relationship between optimism and post-traumatic stress symptoms. Our sample included 1015 participants ranging in age from 18 to 79 years, 80% of whom were Spaniards. At the beginning of the worldwide pandemic, participants were confined to their homes for at least seven days and completed an online survey measuring various sociodemographic and psychological variables. We found an indirect effect of optimism on intrusion and hyperarousal through perceived stress and stress anticipation. In addition, we observed an indirect effect of optimism on avoidance through perceived stress. Finally, the results showed a significant indirect effect of optimism on the total post-traumatic stress symptoms score through perceived stress and stress anticipation. Our results indicate that positive beliefs inherent to optimism are related to less psychological impact of the COVID-19 outbreak.

Effects of HF-rTMS over the left and right DLPFC on proactive and reactive cognitive control.

Previous research supports the distinction between proactive and reactive control. Although the dorsolateral prefrontal cortex (DLPFC) has been consistently related to these processes, lateralization of proactive and reactive control is still under debate. We manipulated brain activity to investigate the role of the left and right DLPFC in proactive and reactive cognitive control. Using a single-blind, sham-controlled crossover within-subjects design, 25 young healthy females performed the 'AX' Continuous Performance Task after receiving sham vs active high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) to increase left and right DLPFC activity. Reaction times (RTs) and pupillometry were used to assess patterns of proactive and reactive cognitive control and task-related resource allocation, respectively. We observed that, compared to sham, HF-rTMS over the left DLPFC increased proactive control. After right DLPFC HF-rTMS, participants showed slower RTs on AX trials, suggesting more reactive control. However, this latter result was not supported by RTs on BX trials (i.e. the trial that specifically assess reactive control). Pupil measures showed a sustained increase in resource allocation after both active left and right HF-rTMS. Our results with RT data provide evidence on the role of the left DLPFC in proactive control and suggest that the right DLPFC is implicated in reactive control.

Hormonal changes of intimate partner violence perpetrators in response to brief social contact with women.

This study investigated whether men with a history of real-life aggressive, dominant behavior show increases in testosterone and cortisol levels after brief social contact with women. Furthermore, we tested the prediction that such changes in hormones would be larger than those observed previously in young male students. Sixty-seven male participants convicted of intimate partner violence (IPV) either had brief social contact with a female confederate (experimental condition) or a male confederate (control condition). We also performed meta-analyses to investigate whether IPV perpetrators' hormonal responses were larger than the typical responses of young male students in prior studies. All statistical analyses were preregistered. Change in testosterone did not differ across experimental conditions, and testosterone in the IPV perpetrators actually declined from baseline in the female confederate condition. Our meta-analysis showed that this testosterone decrease was different from the testosterone increase typically observed in young male students. The cortisol levels of IPV perpetrators did not change in response to contact with women. This result was consistent with our meta-analysis since young male students also did not experience a cortisol change in response to interactions with women. In sum, our findings provide no evidence that male IPV perpetrators exhibit larger hormone increases to brief interactions with women, although it is possible that the men in this sample did not perceive the social contact period as a courtship opportunity. These results suggest that hormone reactivity to social encounters may differ across subject populations and depend on how subjects perceive social situations within laboratory settings.

Mediation of perceived stress and cortisol in the association between neuroticism and global cognition in older adults: A longitudinal study.

Neuroticism has been associated with a greater dementia risk, but its association with cognitive decline in healthy older adults remains unclear. Stress has been proposed as one of the mechanisms that could explain this relationship. Our aim was to analyse, in healthy older people, the mediating role of perceived stress and the Hypothalamic-Pituitary-Adrenal (HPA) axis in the association between neuroticism and global cognition. At Waves 1 and 2 (4-year follow-up), 87 older people (49.4% women; M age = 65.08, SD = 4.54 at Wave 1) completed a neuropsychological battery and the Perceived Stress Scale (PSS), and provided saliva samples on two (Wave 1) and three (Wave 2) consecutive days to measure the wake-to-bed slope. In Wave 2, neuroticism was assessed with the NEO-Five-Factor Inventory. PSS, but not the wake-to-bed slope, mediated the negative associations between neuroticism and global cognition (Waves 1, 2 and change). Regarding gender differences, PSS (Waves 1, 2 and change) and the wake-to-bed slope (Wave 2 and change) mediated these associations in men. Our results suggest that perceived stress and HPA-axis dysregulation could act as mechanisms underlying the association between neuroticism and cognitive functioning and decline, at least in older men.

Reproductive aging and executive functions in healthy women.

The aim of this study was to analyze the influence of reproductive aging on executive functions. We assessed executive functions in three groups of healthy women in the premenopausal (n = 45, mean age = 30.89, SD = 10.5), perimenopausal (n = 31, mean age = 50.06, SD = 3.6) and postmenopausal (n = 24, mean age = 63.39, SD = 6.5) phase. No differences between groups were observed in working memory, verbal fluency, inhibitory control, planning, and cognitive flexibility. However, when the analyses were repeated with participants with occupations with lower intellectual demands, perimenopausal and postmenopausal women performed worse than premenopausal women in semantic verbal fluency. This study provides important evidence to understand the effects of reproductive aging on cognitive performance in healthy women. Our findings indicate that cognitive reserve-related factors may be important to understand the differences in executive functions associated with reproductive aging.

Deficits in facial emotional valence processing in older people with subjective memory complaints: Behavioral and electrophysiological evidence.

Subjective memory complaints (SMCs), which occur in the absence of clinical memory deficits, may precede mild cognitive impairment (MCI) or Alzheimer's disease (AD). Some studies have reported a deficit in facial emotion processing in people with MCI or AD. However, it is unclear whether this deficit is also present in older people with SMCs. The present study used behavioral measurements and event-related potentials (ERPs) to investigate the facial emotion processing of 41 older people with SMCs and 38 without SMCs. The task contained 204 images displaying facial emotions (positive, negative, and neutral). In terms of behavior, our results showed that participants with SMCs were slower and less accurate than controls. In terms of ERPs, the N170 latency was longer in men with SMCs than in controls, whereas no differences were observed between groups in the P300 and late positive potential (LPP) latencies or amplitudes. Moreover, in participants with SMCs, higher P300 and LPP amplitudes were related to better performance on working memory, psychomotor speed, and attention. Additionally, women were faster and more accurate than men on the facial emotion-processing task. In sum, these results suggest that older people with SMCs may have deficits in the processing of facial expressions of emotion. However, this deficit seems to affect the structural encoding of faces, rather than the late stages of processing.

Subjective Memory Complaints and Decision Making in Young and Older Adults: An Event-Related Potential Study.

Subjective memory complaints (SMCs) may affect decision-making processes. This study aimed to investigate the neuronal correlates of feedback processing during a decision-making task in young and older adults with and without SMCs. Event-related potentials and behavioral performance during the Iowa gambling task were recorded in a total of 136 participants (65 young adults, 71 older adults). The participants were divided into two groups according to their SMCs (with SMCs: n = 60, without SMCs: n = 76). Feedback-related negativity (FRN) and P3 were analyzed in the feedback stage of the decision-making process. Older adults with SMCs scored worse in the ambiguity phase than older adults without SMCs. The FRN latency was longer for losses in older people with SMCs than in older people without SMCs in the first block. No significant differences between young and older adults with and without SMCs were observed in the other ERP measures. Compared to young adults, older adults showed delayed latency in the FRN component and reduced amplitudes and delayed latency in the P3 component. In conclusion, older people with SMCs present deficits in the decision-making process. These deficits are observed at the behavioral level, but also in neural mechanisms of early feedback processing of negative outcomes.

Loneliness Mediates the Relationship Between Early Life Stress and Perceived Stress but not Hypothalamic-Pituitary-Adrenal Axis Functioning.

Many authors have proposed that early life stress (ELS) provokes a dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and contributes negatively to the management of stress in adulthood. However, these associations have not always been observed, making it necessary to include new factors that could explain the different results found. In this regard, people with ELS experiences report less social support during adulthood, suggesting that loneliness could be a mediating factor. Thus, our aims were to investigate whether ELS was related to both perceived stress and diurnal HPA axis activity, and whether loneliness mediates these relationships, in a community sample (N=187, 18-55years old). Fourteen cortisol samples were collected on two non-consecutive days to obtain the overall diurnal cortisol, diurnal cortisol slope, and bedtime levels. Additionally, ELS was assessed with the Risky Families Questionnaire (RFQ) and the Recalled Childhood and Adolescence Perceived Stress (ReCAPS) measure. Results revealed that ELS was associated with perceived stress, but not HPA axis functioning, and loneliness mediated the relationship between ELS and perceived stress, but not between ELS and HPA axis functioning. Similar results were found for both ELS questionnaires, suggesting that the ReCAPS is an adequate tool. These results highlight the importance of loneliness in understanding the long-term effects of ELS, and they indicate different effects of ELS on subjective and physiological stress indicators.

Attenuated beta-adrenergic response to stress and increased anticipation and perception of social threat in women high on perceived criticism.

A large amount of literature has demonstrated that Perceived Criticism (PC)-that is, how critical a person believes a given relative is of him or her-is associated with negative clinical outcomes in a broad range of psychiatric disorders (e.g., relapse or recurrence of symptoms). A possible mechanism behind the predictive value of PC might be its association with the stress regulation process. This is the first study to investigate differences in the psychophysiological response to a social stress task in young women (mean age = 21.66, SD = 4.33) with high (n = 40) and low (n = 39) PC. The physiological response was investigated by measuring two markers of sympathetic activity mediated by acetylcholine (skin conductance levels; SCL) and adrenaline (pre-ejection period; PEP) levels, respectively, and one marker of the vagally-mediated parasympathetic system (heart rate variability; HRV). Moreover, we investigated the anticipation and perception of social threat, in the form of criticism, during the stressor. No differences in HRV and SCL were observed. However, individuals high in PC mobilized fewer cardiovascular resources to deal with the stressor, reflected in an attenuated beta-adrenergic response (i.e., lower PEP response). Women high in PC also expected and perceived more criticism during the stress task. Together, our results indicate that women high in PC make heightened social threat anticipation and interpretations, and they tend to engage in less active coping when exposed to socially evaluated stressful events. Our findings indicate that PC is associated with underlying stress-related psychobiological vulnerabilities that may contribute to its association with negative clinical outcomes.

Diurnal cortisol secretion and health-related quality of life in healthy older people.

Several studies have demonstrated that a dysregulated hypothalamic-pituitary-adrenal (HPA) axis is related to worse health status (e.g., depression, posttraumatic stress, or diabetes, among others). However, less is known about the association between the individual's perception of their own health status and HPA-axis functioning in healthy older people. The aim of the present study was to examine the relationship between HPA-axis functioning and health-related quality of life (HRQoL) in healthy older people. To do this, 140 healthy older people (69 men and 71 women) from 56 to 76 years old collected eight saliva samples on two consecutive weekdays to measure the diurnal cortisol cycle (i.e. awakening cortisol levels, cortisol awakening response (CAR), overall morning cortisol levels, change in the cortisol levels during the day, and bedtime cortisol levels). In addition, they completed the SF-36 questionnaire to obtain a measure of HRQoL (i.e. reflecting physical and mental functional health status). Results showed that higher awakening and bedtime cortisol levels and the CAR were associated with a better perception of both physical and mental health. In addition, the wake-to-bed cortisol slope was only positively related to physical health. No sex differences were found. These findings suggest that the awakening and bedtime cortisol levels and the CAR are the most relevant indices of diurnal cortisol secretion for understanding the relationship between HPA-axis functioning and HRQoL status in older people.