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BACKGROUND: Prior research in substance dependence has suggested potential anti-craving effects of repetitive transcranial magnetic stimulation (rTMS) when applied to the dorsolateral prefrontal cortex (DLPFC). However, no single sham-controlled session studies applied to the right DLPFC have been carried-out in recently detoxified alcohol-dependent patients. Furthermore, no studies examined the effect of a single HF-rTMS session on craving in these patients' natural habitat. METHODS: To further investigate the effect of high-frequency (HF)-rTMS of the right DLPFC on alcohol craving, we performed a prospective, single-blind, sham-controlled study involving 36 hospitalized patients with alcohol dependence syndrome. After successful detoxification, patients were allocated receiving one active or one sham HF-rTMS session. The obsessive-compulsive drinking scale (OCDS) was administered to evaluate the extent of craving just before and after the HF-rTMS session (on Friday), on Saturday and Sunday during the weekend at home, and on Monday when the patient returned to the hospital. RESULTS: One single blind sham-controlled HF-rTMS session applied to the right DLPFC did not result in changes in craving (neither immediately after the stimulation session, nor in patients' natural environment during the weekend). CONCLUSIONS: One HF-rTMS stimulation session applied to the right DLPFC had no significant effects on alcohol craving in alcohol dependent patients. One such session could have been too short to alter alcohol craving in a sample of alcohol dependent patients. [ABSTRACT FROM AUTHOR]

The neurovisceral integration model proposes that information flows bidirectionally between the brain and the heart via the vagus nerve, indexed by vagally mediated heart rate variability (vmHRV). Voluntary reduction in breathing rate (slow-paced breathing, SPB, 5.5 Breathing Per Minute (BPM)) can enhance vmHRV. Additionally, prefrontal transcranial direct current stimulation (tDCS) can modulate the excitability of the prefrontal region and influence the vagus nerve. However, research on the combination of SPB and prefrontal tDCS to increase vmHRV and other cardiac (heart rate (HR) and blood pressure) and peripheral (skin conductance) indices is scarce. We hypothesized that the combination of 20 min of SPB and prefrontal tDCS would have a greater effect than each intervention in isolation. Hence, 200 participants were divided into four groups: active tDCS with SPB, active tDCS with 15 BPM breathing, sham tDCS with SPB, and sham tDCS with 15 BPM breathing. Regardless of the tDCS condition, the 5.5 BPM group showed a significant increase in vmHRV over 20 minutes and significant decreases in HR at the first and second 5-min epochs of the intervention. Regardless of breathing condition, the active tDCS group exhibited higher HR at the fourth 5-min epoch of the intervention than the sham tDCS group. No other effects were observed. Overall, SPB is a robust technique for increasing vmHRV, whereas prefrontal tDCS may produce effects that counteract those of SPB. More research is necessary to test whether and how SPB and neuromodulation approaches can be combined to improve cardiac vagal tone., (© 2024 Society for Psychophysiological Research.)

Background: Although psychological factors have been implicated in patients with functional dysphonia (FD), conventional voice therapy (CVT) typically targets the aberrant voice symptoms exclusively. Yet, CVT is not always successful, and in view of the significant adverse quality of life impact combined with the financial burden on the healthcare system and society, research is needed to elucidate the underlying psychophysiology of FD and improve treatment outcomes., Objectives: The first objective of this research project is to compare the occurrence and frequency of symptoms and/or disorders related to autonomic nervous system (ANS) dysfunction in patients with FD with gender- and age-matched vocally healthy controls, using a case-control study. The second objective is to compare the effects of a novel therapy for FD based on ANS regulation (i.e., ANS therapy: heart rate variability (HRV) biofeedback) on both autonomic function and voice function versus CVT alone or in combination with ANS therapy (i.e., ANS therapy + CVT), using a randomized controlled trial (RCT)., Methods: Case-control study: Autonomic (dys)function of patients with FD will be compared with gender- and age-matched vocally healthy controls, using both physiological measures (e.g., HRV, skin conductance level) and psychological patient-reported outcome measures (PROMs, e.g., Neuroception of Psychological Safety Scale, Depression Anxiety and Stress Scale). RCT: The FD group will be randomly assigned to the innovative ANS therapy group, the CVT group or the ANS therapy + CVT group. All patients received 1 month of treatment with 20 min of daily practice. Both the autonomic assessment and the voice assessment will be performed pretherapy and immediately after therapy by assessors blinded to group allocation and study phase., Expected Results: Higher occurrences of symptoms and/or disorders related to autonomic dysfunction are expected in patients with FD compared with vocally healthy controls. Physiological outcomes: lower HRV, lower cardiac pre-ejection period, higher respiration rate and higher skin conductance level are hypothesized in patients with FD compared with vocally healthy controls. Psychological PROMs: higher self-report of feelings/symptoms related to autonomic dysfunction (e.g., perceived stress, anxiety) is expected in patients with FD compared with vocally healthy controls. The autonomic function is hypothesized to improve more after the ANS therapy and the ANS therapy + CVT compared with the CVT only. Voice function is expected to improve more after the ANS therapy + CVT compared with the ANS therapy and the CVT alone., What This Paper Adds: What is already known on the subject Autonomic dysfunction is well recognized in the field of psychology but remains understudied in the area of voice. Given that the vagus nerve, innervating the larynx, also helps to regulate the ANS, and psychological symptoms commonly observed in patients with FD may reflect ANS dysregulation, research in this area is needed. There is some preliminary evidence that autonomic dysfunction might indeed be associated with FD. However, physiological ANS measures are needed, as well as validated psychological PROMs. What this paper adds to the existing knowledge The first objective of this study is to investigate the occurrence and frequency of symptoms and/or disorders related to autonomic dysfunction in patients with FD as compared with a gender- and age-matched vocally healthy control group. Autonomic (dys)function will be determined by employing both physiological measures (e.g., HRV, skin conductance level) and psychological PROMs (e.g., Neuroception of Psychological Safety Scale, Depression Anxiety and Stress Scale). The second objective is to compare the effects of a novel therapy for FD based on ANS regulation (HRV biofeedback) versus CVT alone or in combination with ANS therapy. What are the potential or actual clinical implications of this work? Success rates of symptomatic CVT for FD are highly variable. This study is expected to lead to innovative results related to the pathogenesis and psychophysiology of FD, a prevalent voice disorder associated with a significant adverse quality of life impact and a substantial financial burden on the healthcare system and society. The results of this study will lead to crucial new insights into both the diagnosis and treatment of FD, contributing to evidence-based practice in the field of voice., (© 2024 Royal College of Speech and Language Therapists.)

This paper introduces the Ghent Semi-spontaneous Speech Paradigm (GSSP), a new method for collecting unscripted speech data for affective-behavioral research in both experimental and real-world settings through the description of peer-rated pictures with a consistent affective load. The GSSP was designed to meet five criteria: (1) allow flexible speech recording durations, (2) provide a straightforward and non-interfering task, (3) allow for experimental control, (4) favor spontaneous speech for its prosodic richness, and (5) require minimal human interference to enable scalability. The validity of the GSSP was evaluated through an online task, in which this paradigm was implemented alongside a fixed-text read-aloud task. The results indicate that participants were able to describe images with an adequate duration, and acoustic analysis demonstrated a trend for most features in line with the targeted speech styles (i.e., unscripted spontaneous speech versus scripted read-aloud speech). A speech style classification model using acoustic features achieved a balanced accuracy of 83% on within-dataset validation, indicating separability between the GSSP and read-aloud speech task. Furthermore, when validating this model on an external dataset that contains interview and read-aloud speech, a balanced accuracy score of 70% is obtained, indicating an acoustic correspondence between the GSSP speech and spontaneous interviewee speech. The GSSP is of special interest for behavioral and speech researchers looking to capture spontaneous speech, both in longitudinal ambulatory behavioral studies and laboratory studies. To facilitate future research on speech styles, acoustics, and affective states, the task implementation code, the collected dataset, and analysis notebooks are available., (© 2023. The Author(s).)

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., (© 2024 Society for Psychophysiological Research.)

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., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Importance: Transcranial direct current stimulation (tDCS) is moderately effective for depression when applied by trained staff. It is not known whether self-applied tDCS, combined or not with a digital psychological intervention, is also effective., Objective: To determine whether fully unsupervised home-use tDCS, combined with a digital psychological intervention or digital placebo, is effective for a major depressive episode., Design, Setting, and Participants: This was a double-blinded, sham-controlled, randomized clinical trial with 3 arms: (1) home-use tDCS plus a digital psychological intervention (double active); (2) home-use tDCS plus digital placebo (tDCS only), and (3) sham home-use tDCS plus digital placebo (double sham). The study was conducted between April 2021 and October 2022 at participants' homes and at Instituto de Psiquiatria do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil. Included participants were aged 18 to 59 years with major depression and a Hamilton Depression Rating Scale, 17-item version (HDRS-17), score above 16, a minimum of 8 years of education, and access to a smartphone and internet at home. Exclusion criteria were other psychiatric disorders, except for anxiety; neurologic or clinical disorders; and tDCS contraindications., Interventions: tDCS was administered in 2-mA, 30-minute prefrontal sessions for 15 consecutive weekdays (1-mA, 90-second duration for sham) and twice-weekly sessions for 3 weeks. The digital intervention consisted of 46 sessions based on behavioral therapy. Digital placebo was internet browsing., Main Outcomes and Measures: Change in HDRS-17 score at week 6., Results: Of 837 volunteers screened, 210 participants were enrolled (180 [86%] female; mean [SD] age, 38.9 [9.3] years) and allocated to double active (n = 64), tDCS only (n = 73), or double sham (n = 73). Of the 210 participants enrolled, 199 finished the trial. Linear mixed-effects models did not reveal statistically significant group differences in treatment by time interactions for HDRS-17 scores, and the estimated effect sizes between groups were as follows: double active vs tDCS only (Cohen d, 0.05; 95% CI, -0.48 to 0.58; P = .86), double active vs double sham (Cohen d, -0.20; 95% CI, -0.73 to 0.34; P = .47), and tDCS only vs double sham (Cohen d, -0.25; 95% CI, -0.76 to 0.27; P = .35). Skin redness and heat or burning sensations were more frequent in the double active and tDCS only groups. One nonfatal suicide attempt occurred in the tDCS only group., Conclusions and Relevance: Unsupervised home-use tDCS combined with a digital psychological intervention or digital placebo was not found to be superior to sham for treatment of a major depressive episode in this trial., Trial Registration: ClinicalTrials.gov Identifier: NCT04889976.

Heterogeneity in speech under stress has been a recurring issue in stress research, potentially due to varied stress induction paradigms. This study investigated speech features in semi-guided speech following two distinct psychosocial stress paradigms (Cyberball and MIST) and their respective control conditions. Only negative affect increased during Cyberball, while self-reported stress, skin conductance response rate, and negative affect increased during MIST. Fundamental frequency (F0), speech rate, and jitter significantly changed during MIST, but not Cyberball; HNR and shimmer showed no expected changes. The results indicate that observed speech features are robust in semi-guided speech and sensitive to stressors eliciting additional physiological stress responses, not solely decreases in negative affect. These differences between stressors may explain literature heterogeneity. Our findings support the potential of speech as a stress level biomarker, especially when stress elicits physiological reactions, similar to other biomarkers. This highlights its promise as a tool for measuring stress in everyday settings, considering its affordability, non-intrusiveness, and ease of collection. Future research should test these results' robustness and specificity in naturalistic settings, such as freely spoken speech and noisy environments while exploring and validating a broader range of informative speech features in the context of stress., (© 2024. The Author(s).)

Transcranial direct current stimulation (tDCS) over the prefrontal cortex has the potential to enhance working memory by means of a weak direct current applied to the scalp. However, its effects are highly variable and possibly dependent on individual variability in cortical architecture and head anatomy. Unveiling sources of heterogeneity might improve fundamental and clinical application of tDCS in the field. Therefore, we investigated sources of tDCS variability of prefrontal 1.5 mA tDCS, 3 mA tDCS and sham tDCS in 40 participants (67.5% women, mean age 24.7 years) by associating simulated electric field (E-field) magnitude in brain regions of interest (dorsolateral prefrontal cortex, anterior cingulate cortex (ACC) and subgenual ACC) and working memory performance. Emotional and non-emotional 3-back paradigms were used. In the tDCS protocol analysis, effects were only significant for the 3 mA group, and only for the emotional tasks. In the individual E-field magnitude analysis, faster responses in non-emotional, but not in the emotional task, were associated with stronger E-fields in all brain regions of interest. Concluding, individual E-field distribution might explain part of the variability of prefrontal tDCS effects on working memory performance and in clinical samples. Our results suggest that tDCS effects might be more consistent or improved by applying personalizing current intensity, although this hypothesis should be confirmed by further studies., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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 (vmHRV) provides a non-invasive, surrogate measure of vagal modulation of the heart, and higher HRV is considered an indicator of susceptibility, or ability to respond to stress. Past research has suggested a link between trait rumination and vmHRV; however, inconsistent results exist in healthy individuals. In this study, we investigated the association between the tendency to ruminate, brooding, and reflection (using the Ruminative Response Scale) with vmHRV measured at baseline in a healthy population using a large cross-sectional dataset (N = 1189, 88% female; 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 vmHRV and trait rumination (confirmed by Bayesian analysis), even after controlling for important confounders such as gender, age, and depressive symptoms. Also, a non-linear relationship was rejected. In summary, based on our results in a large sample of healthy individuals, vmHRV is not a marker of trait rumination (as measured by the Ruminative Response Scale)., (© 2023 Society for Psychophysiological Research.)

Sensitivity to criticism, which can be defined as a negative evaluation that a person receives from someone else, is considered a risk factor for the development of psychiatric disorders in adolescents. They may be more vulnerable to social evaluation than adults and exhibit more inadequate emotion regulation strategies such as rumination. The neural network involved in dealing with criticism in adolescents may serve as a biomarker for vulnerability to depression. However, the directions of the functional interactions between the brain regions within this neural network in adolescents are still unclear. In this study, 64 healthy adolescents (aged 14 to 17 years) were asked to listen to a series of self-referential auditory segments, which included negative (critical), positive (praising), and neutral conditions, during fMRI scanning. Dynamic Causal Modeling (DCM) with Parametric Empirical Bayesian (PEB) analysis was performed to map the interactions within the neural network that was engaged during the processing of these segments. Three regions were identified to form the interaction network: the left pregenual anterior cingulate cortex (pgACC), the left dorsolateral prefrontal cortex (DLPFC), and the right precuneus (preCUN). We quantified the modulatory effects of exposure to criticism and praise on the effective connectivity between these brain regions. Being criticized was found to significantly inhibit the effective connectivity from the preCUN to the DLPFC. Adolescents who scored high on the Perceived Criticism Measure (PCM) showed less inhibition of the preCUN-to-DLPFC connectivity when being criticized, which may indicate that they required more engagement of the Central Executive Network (which includes the DLPFC) to sufficiently disengage from negative self-referential processing. Furthermore, the inhibitory connectivity from the DLPFC to the pgACC was strengthened by exposure to praise as well as criticism, suggesting a recruitment of cognitive control over emotional responses when dealing with positive and negative evaluative feedback. Our novel findings contribute to a more profound understanding of how criticism affects the adolescent brain and can help to identify potential biomarkers for vulnerability to develop mood disorders before or during adulthood., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Rumination is conceptualized as a critical transdiagnostic vulnerability and maintenance factor for affective dysregulation and related emotional disorders. Recent research has pointed to transcranial direct current stimulation (tDCS) as a novel therapeutic tool for alleviating rumination, especially stress-induced rumination. However, the mechanisms of action underlying this effect remain unclear, particularly regarding the potential moderating role of executive control and trait-like rumination. Therefore, in this study, we investigated the impact of anodal tDCS on stress-induced rumination and the potential moderating influence of executive control and trait-like rumination on this efect., Method: Forty participants from the general community (i.e., unselected sample) took part in a double-blind within-subjects design study wherein we compared anodal stimulation over the left dorsolateral prefrontal cortex(dlPFC) with a sham-stimulation procedure. Participants completed an N-back task, reflecting executive control, during tDCS stimulation, followed by a stress-induction protocol wherein we assessed stress-induced state rumination., Results: We found no significant effect of tDCS on stress-induced state rumination and no modulation by executive control or trait rumination. Post-hoc Bayesian analyses corroborated these results and even supported the hypothesis that anodal tDCS does not impact stress-induced rumination., Conclusions: From a clinical perspective, our results are at odds with the current outlook that tDCS is a viable tool for reducing rumination, particularly stress-induced rumination. However, we firmly believe that the results of null-finding studies, such as those from this study, are particularly valuable for future iterations and meta-researchon tDCS as a potential tool for targeting transdiagnostic processes, such as rumination. We also addressed methodological limitations and directions for future research in this area., Competing Interests: Competing interests: Dr. Alexandre Heeren receives honoraria for his editorial work from Elsevier. This financial support had no influence on the study design, data collection, analysis, decision to publish, or writing of the article. The other authors declare that they have no conflict of interest., (© 2024 Giovanni Fioriti Editore s.r.l.)

The Cyberball is the most commonly employed paradigm for the investigation of the effects of social exclusion, also called ostracism. The analysis of event-related potentials (ERPs), short-term stimulus-induced fluctuations in the EEG signal, has been employed for the identification of time-sensitive neural responses to ostracism-related information. Changes in ERPs during the Cyberball are normally attributed to the effect of ostracism, but it has been argued that characteristics of the paradigm, not ostracism, are the driving force for these changes. To elucidate the origin of the ERP changes in the Cyberball, we systematically reviewed the Cyberball-ERP literature of healthy, adult populations, and evaluated whether the social context of ostracism or characteristics of the paradigm are better suited for the explanation of the found results. Our results show that for many components no clear origin can be identified, but that expectancy violations, not ostracism, best explains the results of the P3 complex. Future research should therefore also employ other paradigms for the research into the effects of ostracism on ERPs., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: Transcranial direct current stimulation (tDCS) has mixed effects for major depressive disorder (MDD) symptoms, partially owing to large inter-experimental variability in tDCS protocols and their correlated induced electric fields (E-fields). We investigated whether the E-field strength of distinct tDCS parameters was associated with antidepressant effect., Methods: A meta-analysis was performed with placebo-controlled clinical trials of tDCS enrolling MDD patients. PubMed, EMBASE, and Web of Science were searched from inception to March 10, 2023. Effect sizes of tDCS protocols were correlated with E-field simulations (SimNIBS) of brain regions of interest (bilateral dorsolateral prefrontal cortex [DLPFC] and bilateral subgenual anterior cingulate cortex [sgACC]). Moderators of tDCS responses were also investigated., Results: A total of 20 studies were included (21 datasets, 1,008 patients), using 11 distinct tDCS protocols. Results revealed a moderate effect for MDD (g = 0.41, 95%CI 0.18-0.64), while cathode position and treatment strategy were found to be moderators of response. A negative association between effect size and tDCS-induced E-field magnitude was seen, with stronger E-fields in the right frontal and medial parts of the DLPFC (targeted by the cathode) leading to smaller effects. No association was found for the left DLPFC and the bilateral sgACC. An optimized tDCS protocol is proposed., Conclusion: Our results highlight the need for a standardized tDCS protocol in MDD clinical trials., Competing Interests: ARB has a small equity stake in Flowt, whose devices were not used in the present study. The other authors report no conflicts of interest.

Non-invasive brain stimulation (NIBS) probing the dorsolateral prefrontal cortex (DLPFC) has been shown to have little effect on working memory. The variability of NIBS responses might be explained by inter-subject brain anatomical variability. We investigated whether baseline cortical brain thickness of regions of interest was associated with working memory performance after NIBS by performing a secondary analysis of previously published research. Structural magnetic resonance imaging data were analyzed from healthy subjects who received transcranial direct current stimulation (tDCS), intermittent theta-burst stimulation (iTBS), and placebo. Twenty-two participants were randomly assigned to receive all the interventions in a random order. The working memory task was conducted after the end of each NIBS session. Regions of interest were the bilateral DLPFC, medial prefrontal cortex, and posterior cingulate cortex. Overall, 66 NIBS sessions were performed. Findings revealed a negative significant association between cortical thickness of the bilateral dorsolateral prefrontal cortex and reaction time for both tDCS (left: P=0.045, right: P=0.037) and iTBS (left: P=0.007, right: P=0.007) compared to placebo. A significant positive association was found for iTBS and posterior cingulate cortex (P=0.03). No association was found for accuracy. Our findings provide the first evidence that individual cortical thickness of healthy subjects might be associated with working memory performance following different NIBS interventions. Therefore, cortical thickness could explain - to some extent - the heterogeneous effects of NIBS probing the DLPFC.

The prefrontal cortex plays a crucial role in cognitive processes, both during anticipatory and reactive modes of cognitive control. Transcranial Direct Current Stimulation (tDCS) can modulate these cognitive resources. However, there is a lack of research exploring the impact of tDCS on emotional material processing in the prefrontal cortex, particularly in regard to proactive and reactive modes of cognitive control. In this study, 35 healthy volunteers underwent both real and sham tDCS applied to the right prefrontal cortex in a counterbalanced order, and then completed the Cued Emotion Control Task (CECT). Pupil dilation, a measure of cognitive resource allocation, and behavioral outcomes, such as reaction time and accuracy, were collected. The results indicate that, as compared to sham stimulation, active right-sided tDCS reduced performance and resource allocation in both proactive and reactive modes of cognitive control. These findings highlight the importance of further research on the effects of tDCS applied to the right prefrontal cortex on cognitive engagement, particularly for clinical trials utilizing the present electrode montage in combination with cognitive interventions., (© 2023 The Author(s).)

Affective control refers to the ability to regulate emotions and is considered a marker of mental health. Transcranial direct current stimulation (tDCS), a non-invasive brain stimulation technique, holds promise to enhance affective control. In this between-subjects study in healthy individuals, we investigated the effects of bifrontal tDCS on core processes and higher-level markers of affective control. As such, we assessed direct tDCS effects on emotional interference during an affective control task and indirect effects on an instructed reappraisal task afterward. Results showed that the affective control task combined with active tDCS, compared to sham, resulted in enhanced cognitive emotion regulation. Specifically, participants in the active tDCS condition showed an increased propensity to use reappraisal and were more successful in doing so. Moreover, there was reduced vagally mediated heart rate variability indicative of attenuated emotion and self-regulation, in the sham, but not in the active condition. Surprisingly, there were no effects of tDCS on emotional interference during the affective control task, with Bayesian analyses showing extreme evidence against these effects. Nevertheless, there was a positive association between the emotional interference during the affective control task and participants' reappraisal success afterward for the active, but not the sham tDCS condition. The study offers valuable insights to guide future work on combined tDCS with affective control tasks or training on the ability to regulate emotions., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Previous research has shown that patients with anorexia nervosa (AN) show an attentional bias to food. However, due to different conceptualizations of attentional bias and the use of various paradigms, results are inconclusive and more precise insights into the exact nature of this attentional bias are needed. Therefore, an eye-tracking paradigm with food (low and high caloric) and non-food (objects) pictures was used to investigate biases in AN patients (n = 25) compared to healthy controls (n = 22). Several indices of visual attention were examined, both during free (initial orientation, fixation frequency, fixation time) and explicitly instructed (engagement, disengagement) viewing. Our results during the free viewing phase indicated that AN patients (as compared to healthy matched controls) looked less frequently and spent less time fixating on food stimuli, compared to the comparison group. No differences between both groups (n = 47) in initial orientation could be observed. Interestingly, during the instructed viewing phase, no differences between the patient and the comparison group were observed in engagement or disengagement to food stimuli. These results suggest an (initial) attentional avoidance of food in AN patients when closely investigating spontaneous attentional processes, while this could not be observed during gaze behaviour when receiving clear instructions. Hence, future research should look into how attentional bias during spontaneous gaze patterns could serve as a potential marker of AN, and how targeting this bias could be applied in treatment interventions., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Perseverative cognitions can provoke psychophysiological stress in the absence of an actual stressor and are considered important transdiagnostic vulnerability factors for several (mental) health issues. These stress-related cognitive processes are reflected by both cognitive (assessed by self-reports) and autonomic inflexibility (assessed by heart rate variability; HRV), with a key role attributed to the vagus nerve. Interestingly, modulation of the afferent branches of the vagus can be achieved with transcutaneous auricular vagus nerve stimulation (taVNS), a non-invasive technique that employs a low-intensity electrical current applied to the ear. In a sample of healthy individuals, we investigated the effects of taVNS of the left concha, compared to sham (earlobe) stimulation, on the cognitive and autonomic correlates of perseverative cognition following a psychosocial stress task. Interestingly, taVNS significantly reduced cognitive rigidity, reflected by reduced subjective perseverative thinking after psychosocial stress. Although there were no direct effects on autonomic correlates of perseverative cognition, individual differences in perseverative thinking after the stressor significantly affected the effects of taVNS on HRV. Specifically, more autonomic inflexibility during the stress task (i.e., reduced HRV) was associated with increases in perseverative thinking afterward for the sham condition, but not the active taVNS condition. Additional exploratory analyses revealed no significant moderation of stimulation intensity. Overall, the study findings endorse the association between perseverative cognitions and vagus nerve functioning., (© 2023 Society for Psychophysiological Research.)

The usage of EEG to uncover the influence of psychosocial stressors (PSSs) on neural activity has gained significant attention throughout recent years, but the results are often troubled by confounding stressor types. To investigate the effect of PSSs alone on neural activity, we employed a paradigm where participants are exposed to negative peer comparison as PSS, while other possible stressors are kept constant, and compared this with a condition where participants received neutral feedback. We analyzed commonly used sensor level EEG indices (frontal theta, alpha, and beta power) and further investigated whether source level power and functional connectivity (i.e., the temporal dependence between spatially seperated brain regions) measures, which have to our knowledge not yet been used, are more sensitive to PSSs than sensor level-derived EEG measures. Our results show that on sensor level, no significant frontal power changes are present (all p's > 0.16), indicating that sensor level frontal power measures are not sensitive enough to be affected by only PSSs. On source level, we find increased alpha power (indicative of decreased cortical activity) in the left- and right precuneus and right posterior cingulate cortex (all p's < 0.03) and increased functional connectivity between the left- and right precuneus (p < 0.001), indicating that acute, trial based PSSs lead to decreased precuneus/PCC activity, and possibly indicates a temporary disruption in the self-referential neural processes of an individual., (© 2023. The Author(s).)

Although it is well known that exercise reduces depressive symptoms, the underlying psychological mechanisms remain unclear. This experimental study examined the acute effect of exercise on mood, and depressotypic memory bias and state rumination. Trait rumination was tested as a possible moderator. A sample of non-regular exercisers ( N  = 100) was randomized to exercise or rest. After a negative mood induction, the exercise condition cycled for 24 min at moderate intensity, while the rest condition rested. Negative and overgeneral memory bias, as well as positive and negative affect were assessed after exercise/rest. To capture the lingering of negative mood and state rumination, both were assessed multiple times throughout the study. The exercise (as compared to rest) condition reported more positive affect. However, no differences were found on overgeneral memory bias, as well as depression-specific mood or state rumination measured throughout the study. Interestingly, the exercise condition showed more negative memory bias at higher levels of rumination. Individual differences in trait rumination moderated the exercise-memory bias relation, such that exercise increased negative memory bias at higher levels of rumination. It is possible that long-term exercise protocols are necessary to change cognitive processes related to depression.

Health research and health care alike are presently based on infrequent assessments that provide an incomplete picture of clinical functioning. Consequently, opportunities to identify and prevent health events before they occur are missed. New health technologies are addressing these critical issues by enabling the continual monitoring of health-related processes using speech. These technologies are a great match for the healthcare environment because they make high-frequency assessments non-invasive and highly scalable. Indeed, existing tools can now extract a wide variety of health-relevant biosignals from smartphones by analyzing a person's voice and speech. These biosignals are linked to health-relevant biological pathways and have shown promise in detecting several disorders, including depression and schizophrenia. However, more research is needed to identify the speech signals that matter most, validate these signals against ground-truth outcomes, and translate these data into biomarkers and just-in-time adaptive interventions. We discuss these issues herein by describing how assessing everyday psychological stress through speech can help both researchers and health care providers monitor the impact that stress has on a wide variety of mental and physical health outcomes, such as self-harm, suicide, substance abuse, depression, and disease recurrence. If done appropriately and securely, speech is a novel digital biosignal that could play a key role in predicting high-priority clinical outcomes and delivering tailored interventions that help people when they need it most., Competing Interests: Conflict of Interest The authors declare no conflicts of interest with respect to this work., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: As part of repetitive negative thinking (RNT), rumination is a maladaptive cognitive response style to stress or negative mood which can increase the risk of depression and may prohibit complete recovery. Cognitive behavioral therapy (CBT) and transcranial direct current stimulation (tDCS) both proved to be effective in decreasing rumination. However, the combined effects of tDCS and CBT interventions on rumination have not yet been explored. The first aim of this pilot study is to investigate whether the combination of tDCS and CBT has an accumulating positive effect on modulating state rumination. The second aim is to assess the feasibility and safety profile of the proposed combined approach., Method: Seventeen adults aged 32-60 years, suffering from RNT, were referred by their primary care professional to participate in an 8-week group intervention for RNT ("Drop It") comprising 8 sessions of CBT. Before each CBT session, patients underwent one double-blinded prefrontal active (2 mA for 20 min) or sham tDCS (anode over F3, cathode over the right supraorbital region) combined with an internal cognitive attention task focused on individual RNT, i.e., online tDCS priming. During each session, the Brief State Rumination Inventory was used to assess state rumination., Results: A mixed effects model analysis revealed no significant differences between the stimulation conditions, weekly sessions, or their interaction in terms of state rumination scores., Conclusion: Overall, the combination of online tDCS priming followed by group CBT was found to be safe and feasible. On the other hand, no significant additional effects of this combined approach on state rumination were established. Although our pilot study may have been too small to find significant clinical effects, future larger RCT studies on combined tDCS-CBT treatment protocols may reevaluate the selection of internal cognitive attention tasks and more objective neurophysiological measurements, consider the optimal timing of the combination (concurrently or sequentially), or may add additional tDCS sessions when following CBT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Horczak, Wang, De Witte, De Smet, Remue, De Raedt, Vanderhasselt, Wu, Lemmens and Baeken.)

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..

Non-invasive brain stimulation (NIBS) techniques have been increasingly used over the dorsolateral prefrontal cortex (DLPFC) to enhance working memory (WM) performance. Notwithstanding, NIBS protocols have shown either small or inconclusive cognitive effects on healthy and neuropsychiatric samples. Therefore, we assessed working memory performance and safety of transcranial direct current stimulation (tDCS), intermittent theta-burst stimulation (iTBS), and both therapies combined vs placebo over the neuronavigated left DLPFC of healthy participants. Twenty-four subjects were included to randomly undergo four sessions of NIBS, once a week: tDCS alone, iTBS alone, combined protocol and placebo. The 2-back task and an adverse effect scale were applied after each NIBS session. Results revealed a significantly faster response for iTBS ( b= -21.49, p= 0.04 ), but not for tDCS and for the interaction tDCS vs. iTBS ( b= 13.67, p= 0.26 and b= 40.5, p= 0.20, respectively ). No changes were observed for accuracy and no serious adverse effects were found among protocols. Although tolerable, an absence of synergistic effects for the combined protocol was seen. Nonetheless, future trials accessing different outcomes for the combined protocols, as well as studies investigating iTBS over the left DLPFC for cognition and exploring sources of variability for tDCS are encouraged., Competing Interests: The other authors have no conflicts of interest to disclose., (© 2022 The Authors.)

Transcranial direct current stimulation (tDCS) has been showing promising effects for the treatment of obsessive-compulsive disorder (OCD), but there is still no conclusion on its efficacy for this disorder. We performed a systematic review and meta-analysis of trials using tDCS for OCD and a computer modeling analysis to evaluate the electric field (EF) strengths of different electrode assemblies in brain regions of interest (ROIs) (PROSPERO-42021262465). PubMed/MEDLINE, Embase, Cochrane Library and Web of Science databases were searched from inception to 25 September 2022. Randomized controlled trials (RCTs) and open-label studies were included. The primary aim was the effect size (Hedges' g) of continuous outcomes and potential moderators of response. For EF modeling, SimNIBS software was used. Four RCTs and four open-label trials were included ( n = 241). Results revealed a large effect of tDCS in the endpoint, but no significant effect between active and sham protocols. No predictor of response was found. EF analysis revealed that montages using the main electrode over the (pre)supplementary motor area with an extracephalic reference electrode might lead to stronger EFs in the predefined ROIs. Our results revealed that tDCS might be a promising intervention to treat OCD; however, larger studies are warranted.

The use of speech as a digital biomarker to detect stress levels is increasingly gaining attention. Yet, heterogeneous effects of stress on specific acoustic speech features have been observed, possibly due to previous studies' use of different stress labels/categories and the lack of solid stress induction paradigms or validation of experienced stress. Here, we deployed a controlled, within-subject psychosocial stress induction experiment in which participants received both neutral (control condition) and negative (negative condition) comparative feedback after solving a challenging cognitive task. This study is the first to use a (non-actor) within-participant design that verifies a successful stress induction using both self-report (i.e., decreased reported valence) and physiological measures (i.e., increased heart rate acceleration using event-related cardiac responses during feedback exposure). Analyses of acoustic speech features showed a significant increase in Fundamental Frequency (F0) and Harmonics-to-Noise Ratio (HNR), and a significant decrease in shimmer during the negative feedback condition. Our results using read-out-loud speech comply with earlier research, yet we are the first to validate these results in a well-controlled but ecologically-valid setting to guarantee the generalization of our findings to real-life settings. Further research should aim to replicate these results in a free speech setting to test the robustness of our findings for real-world settings and should include semantics to also take into account what you say and not only how you say it., (© 2022. The Author(s).)

Since the inclusion of Premenstrual Dysphoric Disorder (PMDD) as a mood disorder in the DSM-5, Premenstrual Syndrome (PMS) symptoms have received more attention from researchers and clinicians. In this large-scale study, we investigated core psychological concepts relevant to mood disorder vulnerability between people with 1) no to mild, 2) moderate to severe, and 3) PMDD levels of PMS symptoms. Several trait measures related to mood disorders including depressive symptoms, feelings of stress and anxiety, and ruminative thinking were measured (single measurement, N = 380) along with state (momentary) reports of stress and stress-related perseverative thinking (measured twice, once in the follicular and once in the premenstrual/luteal phase, N = 237). We consistently observed that participants with higher severity of PMS symptoms also scored higher on depression, anxiety, stress, and rumination (trait measures). We also found consistent increases in momentary stress and stress-related perseverative ruminative thinking with increased PMS symptoms at each of our two test moments (in the middle of the follicular and premenstrual/luteal phase respectively). Interestingly, we did not find significant differences between our two test moments for any group, despite PMS being characterized by specific systems in the premenstrual/luteal phase. However, this could be due to noise surrounding the testing moments due to the temporal resolution of the questionnaires and the menstrual cycle estimation method. Nevertheless, these results suggest that stress and rumination are important psychological mechanisms to consider in PMS. Future PMS research studying stress and rumination on a day-to-day basis in combination with hormonal measures is warranted., Competing Interests: Declaration of competing interest The authors declare no possible conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Recent advances in social neuroscience have highlighted the critical role of the cerebellum in social cognition, and especially the posterior cerebellum. Studies have supported the view that the posterior cerebellum builds internal action models of our social interactions to predict how other people's actions will be executed and what our most likely responses are to these actions. This mechanism allows to better anticipate action sequences during social interactions in an automatic and intuitive way and to fine-tune these anticipations, making it easier to understand other's social behaviors and mental states (e.g., beliefs, intentions, traits). In this paper, we argue that the central role of the posterior cerebellum in identifying and automatizing social action sequencing provides a fruitful starting point for investigating social dysfunctions in a variety of clinical pathologies, such as autism, obsessive-compulsive and bipolar disorder, depression, and addiction. Our key hypothesis is that dysfunctions of the posterior cerebellum lead to under- or overuse of inflexible social routines and lack of plasticity for learning new, more adaptive, social automatisms. We briefly review past research supporting this view and propose a program of research to test our hypothesis. This approach might alleviate a variety of mental problems of individuals who suffer from inflexible automatizations that stand in the way of adjustable and intuitive social behavior, by increasing posterior cerebellar plasticity using noninvasive neurostimulation or neuro-guided training programs., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Although relatively costly and non-scalable, non-invasive neuromodulation interventions are treatment alternatives for neuropsychiatric disorders. The recent developments of highly-deployable transcranial electric stimulation (tES) systems, combined with mobile-Health technologies, could be incorporated in digital trials to overcome methodological barriers and increase equity of access. The study aims are to discuss the implementation of tES digital trials by performing a systematic scoping review and strategic process mapping, evaluate methodological aspects of tES digital trial designs, and provide Delphi-based recommendations for implementing digital trials using tES., Methods: We convened 61 highly-productive specialists and contacted 8 tES companies to assess 71 issues related to tES digitalization readiness, and processes, barriers, advantages, and opportunities for implementing tES digital trials. Delphi-based recommendations (>60% agreement) were provided., Results: The main strengths/opportunities of tES were: (i) non-pharmacological nature (92% of agreement), safety of these techniques (80%), affordability (88%), and potential scalability (78%). As for weaknesses/threats, we listed insufficient supervision (76%) and unclear regulatory status (69%). Many issues related to methodological biases did not reach consensus. Device appraisal showed moderate digitalization readiness, with high safety and potential for trial implementation, but low connectivity., Conclusions: Panelists recognized the potential of tES for scalability, generalizability, and leverage of digital trials processes; with no consensus about aspects regarding methodological biases., Significance: We further propose and discuss a conceptual framework for exploiting shared aspects between mobile-Health tES technologies with digital trials methodology to drive future efforts for digitizing tES trials., (Copyright © 2022 International Federation of Clinical Neurophysiology. All rights reserved.)

Major Depressive Disorder (MDD) is a widespread mental illness that causes considerable suffering, and neuroimaging studies are trying to reduce this burden by developing biomarkers that can facilitate detection. Prior fMRI- and neurostimulation studies suggest that aberrant subgenual Anterior Cingulate (sgACC)-dorsolateral Prefrontal Cortex (DLPFC) functional connectivity is consistently present within MDD. Combining the need for reliable depression markers with the electroencephalogram's (EEG) high clinical utility, we investigated whether aberrant EEG sgACC-DLPFC functional connectivity could serve as a marker for depression. Source-space Amplitude Envelope Correlations (AEC) of 20 MDD patients and 20 matched controls were contrasted using non-parametric permutation tests. In addition, extracted AEC values were used to (a) correlate with characteristics of depression and (b) train a Support Vector Machine (SVM) to determine sgACC-DLPFC connectivity's discriminative power. FDR-thresholded statistical maps showed reduced sgACC-DLPFC AEC connectivity in MDD patients relative to controls. This diminished AEC connectivity is located in the beta-1 (13-17 Hz) band and is associated with patients' lifetime number of depressive episodes. Using extracted sgACC-DLPFC AEC values, the SVM achieved a classification accuracy of 84.6% (80% sensitivity and 89.5% specificity) indicating that EEG sgACC-DLPFC connectivity has promise as a biomarker for MDD., (© 2022. The Author(s).)

Non-invasive brain stimulation (NIBS) interventions are promising for the treatment of psychiatric disorders. Notwithstanding, the NIBS mechanisms of action over the dorsolateral prefrontal cortex (DLPFC), a hub that modulates affective and cognitive processes, have not been completely mapped. We aimed to investigate regional cerebral blood flow (rCBF) changes over the DLPFC and the subgenual anterior cingulate cortex (sgACC) of different NIBS protocols using Single-Photon Emission Computed Tomography (SPECT). A factorial, within-subjects, double-blinded study was performed. Twenty-three healthy subjects randomly underwent four sessions of NIBS applied once a week: transcranial direct current stimulation (tDCS), intermittent theta-burst stimulation (iTBS), combined tDCS + iTBS and placebo. The radiotracer 99m-Technetium-ethylene-cysteine-dimer was injected intravenously during the NIBS session, and SPECT neuroimages were acquired after the session. Results revealed that the combination of tDCS + iTBS increased right sgACC rCBF. Cathodal and anodal tDCS increased and decreased DLPFC rCBF, respectively, while iTBS showed no significant changes compared to the placebo. Our findings suggest that the combined protocol might optimize the activity in the right sgACC and encourage future trials with neuropsychiatric populations. Moreover, mechanistic studies to investigate the effects of tDCS and iTBS over the DLPFC are required.

Whereas emotion regulation (ER) in response to distressing events is widely studied, the mechanisms underlying adaptive ER while anticipating these events are still unknown. In this study, we investigated how ER strategies and expectation influence (a) individuals' anticipatory and online processing of self-relevant events, and (b) their affective response to them. Sixty-one healthy female participants were exposed to bogus positive and negative social feedback under reappraisal (regulation) and watch (no regulation) instructions. During the anticipatory period, participants were either expecting negative feedback or they had no expectation regarding the valence of the upcoming self-relevant feedback. Hence, negative feedback was, respectively, expected or unexpected. Participants' affective responses were collected via self-report and electromyographic (EMG) activity over the corrugator muscle. Results showed that participants' negative affect (based on both self-reports and EMG) was reduced by the instructions to reappraise as compared to the watch condition. Yet, such beneficial effect of reappraisal was: (a) not observed during the anticipation phase, and (b) less effective when social feedback was expected (as compared to not expected) prior to its presentation. Possibly, cognitive reappraisal might be less able to overcome the influence of negative forecasting of self-relevant negative emotional stimuli. Research findings are discussed in light of potential mechanisms underlying impaired adaptive ER in patients vulnerable for mood disorders. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Background: Transcranial electrical stimulation (tES) is considered effective and safe for depression, albeit modestly, and prone to logistical burdens when performed in external facilities. Investigation of portable tES (ptES), and potentiation of ptES with remote psychological interventions have shown positive, but preliminary, results., Research Design: We report the rationale and design of an ongoing multi-arm, randomized, double-blind, sham-controlled clinical trial with digital features, using ptES and internet-based behavioral therapy (iBT) for major depressive disorder (MDD) (NCT04889976)., Methods: We will evaluate the efficacy, safety, tolerability and usability of (1) active ptES + active iBT ('double-active'), (2) active ptES + sham iBT ('ptES-only'), and (3) sham ptES + sham iBT ('double-sham'), in adults with MDD, with a Hamilton Depression Rating Scale - 17 item version (HDRS-17) score ≥ 17 at baseline, during 6 weeks. Antidepressants are allowed in stable doses during the trial., Results: We primarily co-hypothesize changes in HDRS-17 will be greater in (1) 'double-active' compared to 'ptES-only,' (2) 'double-active' compared to 'double-sham,' and (3) 'ptES-only' compared to 'double-sham.' We aim to enroll 210 patients (70 per arm)., Conclusions: Our results should offer new insights regarding the efficacy and scalability of combined ptES and iBT for MDD, in digital mental health.

Whereas the link between psychosocial stress and health complications has long been established, the influence of psychosocial stress on brain activity is not yet completely understood. Electroencephalography (EEG) has been regularly employed to investigate the neural aspects of the psychosocial stress response, but these results have not yet been unified. Therefore, in this article, we systematically review the current EEG literature in which spectral analyses were employed to investigate the neural psychosocial stress response and interpret the results with regard to the three stress phases (anticipatory, reactive, and recovery) in which the response can be divided. Our results show that three EEG measures, alpha power, beta power and frontal alpha asymmetry (FAA), are commonly utilized and that alpha power consistently decreases, beta power shows a tendency to increase, and FAA varies inconsistently. We furthermore found that whereas changes in alpha power are independent of the stress phase, and changes in beta power show a relative stress phase independent trend, other EEG measures such as delta power, theta power, relative gamma and theta-alpha power ratio show less stress phase independent changes. Meta-analyses conducted on alpha power, beta power and FAA further revealed a significant effect size (hedge's g = 0.6; p = 0.001) for alpha power, but an insignificant effect size for beta power (hedge's g = -0.31; p = 0.29) and FAA (hedge's g = 0.01, p = 0.93). From our results, it can be concluded that psychosocial stress results in significant changes in some spectral EEG indices, but that more research is needed to further uncover the precise (temporal) mechanisms underlying these neural responses., Competing Interests: Ir. G. V. was supported by a grant from the 10.13039/501100007229Bijzonder Onderzoeksfonds (BOF) (Grant Number: BOFSTA2017002501) from the university of Ghent. S.D.S was supported by a grant from the Fonds Wetenschappelijk Onderzoek Vlaanderen (FWO-Flanders) (Grant Number: 11J7521N). All authors report no other financial interests of potential conflicts of interest related to this publication., (© 2022 The Authors.)

Recently, the possibilities of detecting psychosocial stress from speech have been discussed. Yet, there are mixed effects and a current lack of clarity in relations and directions for parameters derived from stressed speech. The aim of the current study is - in a controlled psychosocial stress induction experiment - to apply network modeling to (1) look into the unique associations between specific speech parameters, comparing speech networks containing fundamental frequency (F0), jitter, mean voiced segment length, and Harmonics-to-Noise Ratio (HNR) pre- and post-stress induction, and (2) examine how changes pre- versus post-stress induction (i.e., change network) in each of the parameters are related to changes in self-reported negative affect. Results show that the network of speech parameters is similar after versus before the stress induction, with a central role of HNR, which shows that the complex interplay and unique associations between each of the used speech parameters is not impacted by psychosocial stress (aim 1). Moreover, we found a change network (consisting of pre-post stress difference values) with changes in jitter being positively related to changes in self-reported negative affect (aim 2). These findings illustrate - for the first time in a well-controlled but ecologically valid setting - the complex relations between different speech parameters in the context of psychosocial stress. Longitudinal and experimental studies are required to further investigate these relationships and to test whether the identified paths in the networks are indicative of causal relationships., (© 2021. The Author(s).)

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., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The left dorsolateral prefrontal cortex (lDLPFC) is implicated in anticipatory (i.e. during anticipation of emotional stimuli) and online (i.e. during confrontation with emotional stimuli) emotion regulatory processes. However, research that investigates the causal role of the lDLPFC in these processes is lacking. In this study, 74 participants received active or sham transcranial direct current stimulation (tDCS) over the lDLPFC. Participants were told strangers evaluated them. These (rigged) social evaluations were presented, and in 50% of the trials, participants could anticipate the valence (positive or negative) of the upcoming social feedback. Pupil dilation (a marker of cognitive resource allocation) and skin conductance responses (a marker of arousal) were measured. The results indicate that active (compared to sham) tDCS reduced arousal during the confrontation with anticipated feedback but only marginally during the confrontation with unanticipated feedback. When participants were given the opportunity to anticipate the social feedback, tDCS reduced arousal, irrespective of whether one was anticipating or being confronted with the anticipated feedback. Moreover, tDCS reduced cognitive resource allocation during anticipation, which was associated with resource allocation increases during the subsequent confrontation. Altogether, results suggest that the lDLPFC is causally implicated in the interplay between anticipatory and online emotion regulatory processes., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: There is active interest in biomarker discovery for transcutaneous auricular vagus nerve stimulation (taVNS). However, greater understanding of the neurobiological mechanisms is needed to identify candidate markers. Accumulating evidence suggests that taVNS influences activity in solitary and parabrachial nuclei, the primary brainstem relays for the transmission of visceral sensory afferents to the insula. The insula mediates interoception, which concerns the representation and regulation of homeostatic bodily states. Consequently, interoceptive pathways may be relevant to taVNS mechanisms of action., Hypotheses: We hypothesized that taVNS would modulate an EEG-derived marker of interoceptive processing known as the heart-evoked potential (HEP). We also hypothesized that taVNS-induced HEP effects would be localizable to the insula., Methods: Using a within-subject, sham-controlled design, we recorded EEG and ECG concurrent to taVNS in 43 healthy adults. Using ECG and EEG data, we extracted HEPs. Estimation of the cortical sources of the taVNS-dependent HEP responses observed at the scalp were computed using the Boundary Element Method and weighted Minimum Norm Estimation. Statistics were calculated using cluster-based permutation methods., Results: taVNS altered HEP amplitudes at frontocentral and centroparietal electrode sites at various latencies. The taVNS-dependent HEP effect was localized to the insula, operculum, somatosensory cortex, and orbital and ventromedial prefrontal regions., Conclusion: The results support the hypothesis that taVNS can access the insula as well as functionally and anatomically connected brain regions. HEPs may serve as an objective, non-invasive outcome parameter for the cortical effects of taVNS., (Copyright © 2021. Published by Elsevier Inc.)

Chronic stress has dramatically increased over the last years and is one of the major health concerns of the 21st century. Targeted interventions are traditionally based on inducing cognitive changes and enhancing control with the aim to promote adaptive emotion regulation, ultimately enhancing stress resilience. Crucially, bodily functions have received little attention in this quest, despite increasing evidence on the impact of mind-body interactions on resilience. An exemplary model is constituted by accumulating empirical support on the vagus nerve, which enables two-way communication between heart and brain, allowing to engage in an adaptive stress response in a context-appropriate manner. Yet, research on such bidirectional communication is mainly correlational. We propose to consider resonance breathing (bottom-up approach, heart > brain), and neuromodulation (top-down approach, brain > heart) as evidence-based ways to increase vagal nerve inhibitory control and hence increase stress resilience. These promising, likely cost-effective and easily employable techniques can be used alone or in combination, harnessing neurobiological scientific advances to select treatment options with the greatest likelihood of success., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Continuation or maintenance electroconvulsive therapy (C/M-ECT) is recommended to reduce relapse rates of patients with major depressive disorder. During the ongoing COVID-19 pandemic, ECT services have come under pressure or needed to close because of redirected resources and safety reasons. We investigated the impact of C/M-ECT discontinuation on relapse in patients with unipolar depressive disorder in Flanders, Belgium., Methods: Between March 30 and June 18, 2020, all patients receiving C/M-ECT in 2 ECT centers were included. Continuation or maintenance electroconvulsive therapy was discontinued in 33 patients and continued in 4 patients. Relapse was defined as the need to restart ECT or the need for hospitalization. Depressive symptoms were assessed every 3 weeks using the Patient Health Questionnaire, the Clinical Global Impression Scale, and 2 additional patient-rated questions., Results: Relapse in the discontinuation group was 60.6%. All 4 patients who continued ECT remained remitted. Kaplan-Meier survival analysis showed significantly shorter relapse rates for patients receiving bitemporal and/or frequent C/M-ECT (1- to 2-week intervals). Patients older than 60 years showed longer survival rates., Conclusions: Our results confirm earlier prospective and retrospective data regarding the efficacy and importance of C/M-ECT as relapse prevention. After treatment discontinuation, close monitoring of early warning signs for relapse is crucial, especially in the first few months. With the COVID-19 pandemic continuing, our data provide an indication of the necessity to ensure adequate care and access to ECT not only for the acutely ill but also for the vulnerable patients who are depending on C/M-ECT., Competing Interests: The authors have no conflicts of interest or financial disclosures to report., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Transcranial direct current stimulation (tDCS) and mindfulness practices have been proposed as a potential approach to improve executive functions (EFs) and reduce craving in persons with substance use disorders. Based on the neural mechanisms of action of each of these interventions, the combination of both non-pharmacological interventions might have additive effects. In the current study, the effects of tDCS combined with mindfulness-based substance abuse treatment (MBSAT) to improve EFs and reduce craving were investigated in early abstinent methamphetamine abuse., Methods: Eighty (youths aged between 18 and 21) early-abstinent methamphetamine users were randomly assigned to the research groups (tDCS group [n = 20], mindfulness group [n = 20], combined mindfulness-tDCS group [n = 20], and sham group [n = 20]). Active tDCS (1.5 mA,20 min, 12 sessions) or sham tDCS was appliedover the left dorsolateral prefrontal cortex and the MBSAT protocol was used over twelve 50-min sessions., Results: Both in the post-test phase (immediately after the intervention) and follow-up phase (one month after the intervention), performance in most EFs tasks significantly improved in the combination group which received real tDCS ＋ MBSAT, as compared to baseline values and sham stimulation group. Similarly, a significant reduction in craving was observed after intervention inall treatment groups, but not the sham stimulation group. Interestingly, the increase in EFs and the reduction in craving post versus pre tDCS ＋ MBSAT intervention were correlated., Conclusion: Findings from the current study provide initial support for the clinical effectiveness of combination tDCS ＋ MBSAT, possibly influencing cognitive/affective processes.

Background: Already a major health concern, late-life depression (LLD) is expected to form an increasing problem in the aging population. Moreover, despite current treatments, LLD is associated with a poor long-term prognosis and high rate of chronicity. Treatment provision and treatment accordingly warrant improvement, where add-on treatments might contribute to the efficacy of conventional therapies. Although it is known that impaired cognitive control contributes to LDD, it is not targeted sufficiently by current interventions. Research on cognitive control training (CCT) shows promising results on depressive symptoms, cognitive performance, and overall functioning. However, further research is needed to determine the long-term effects of CCT on LLD, its cost-effectiveness, and mechanisms of change., Methods: In the current multicenter randomized controlled trial (RCT) with a between-subjects design participants aged 60 years and over with a current LLD receiving treatment as usual (TAU) are randomized to add-on CCT or placebo training. Randomization is stratified by depression severity. Participants will receive eight online CCT or placebo sessions spread across four consecutive weeks. They will complete a post-training assessment after 1 month and three follow-up assessments scheduled three, six and 12 months after completing the training. We expect CCT and TAU to be more (cost-)effective in reducing depressive symptoms than placebo training and TAU. Additionally, we will be looking at secondary clinical, cognitive and global functioning outcomes and likely mechanisms of change (e.g., improved cognitive functioning, reduced rumination, and improved inhibition of negative stimuli)., Discussion: The proposed RCT aims to contribute to the clinical and scientific knowledge on the long-term effects of CCT as an add-on treatment for LLD. Cost-effectiveness is particularly relevant considering the expected volume of the target demographic. The study will be a pragmatic trial with few inclusion restrictions, providing information on feasibility of web-based trainings in clinical settings. The outcomes are potentially generalizable to guidelines for treatment of LLD., Trial Registration: This trial is registered in the Netherlands Trial Register (code: NL7639 ). Registered 3 april 2019., (© 2021. The Author(s).)

Background: Approximately half of all people with alcohol use disorder (AUD) relapse into alcohol reuse in the next few weeks after a withdrawal treatment. Brain stimulation and cognitive training represent recent forms of complementary interventions in the context of AUD., Objective: To evaluate the clinical efficacy of five sessions of 2 mA bilateral transcranial direct current stimulation (tDCS) for 20 min over the dorsolateral prefrontal cortex (DLPFC) (left cathodal/right anodal) combined with alcohol cue inhibitory control training (ICT) as part of rehabilitation. The secondary outcomes were executive functioning (e.g. response inhibition) and craving intensity, two mechanisms strongly related to abstinence., Methods: A randomized clinical trial with patients (n = 125) with severe AUD at a withdrawal treatment unit. Each patient was randomly assigned to one of four conditions, in a 2 [verum vs. sham tDCS] x 2 [alcohol cue vs. neutral ICT] factorial design. The main outcome of treatment was the abstinence rate after two weeks or more (up to one year)., Results: Verum tDCS improved the abstinence rate at the 2-week follow-up compared to the sham condition, independently of the training condition (79.7% [95% CI = 69.8-89.6] vs. 60.7% [95% CI = 48.3-73.1]; p = .02). A priori contrasts analyses revealed higher abstinence rates for the verum tDCS associated with alcohol cue ICT (86.1% [31/36; 95% CI = 74.6-97.6]) than for the other three conditions (64% [57/89; 95% CI = 54-74]). These positive clinical effects on abstinence did not persist beyond two weeks after the intervention. Neither the reduction of craving nor the improvement in executive control resulted specifically from prefrontal-tDCS and ICT., Conclusions: AUD patients who received tDCS applied to DLPFC showed a significantly higher abstinence rate during the weeks following rehabilitation. When combined with alcohol specific ICT, brain stimulation may provide better clinical outcomes., Trial Registration: ClinicalTrials.gov number NCT03447054 https://clinicaltrials.gov/ct2/show/NCT03447054., Competing Interests: Declaration of competing interest This study is part of Macha Dubuson Ph.D thesis. Dr Kornreich reported receiving grants from the King Baudouin Foundation and the CHU Brugmann Foundation during the study. Dubuson reported receiving salary support through grants of the King Baudouin Foundation and the Brugmann Foundation during the study. There are no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Non-invasive brain stimulation (NIBS) as monotherapy has been increasingly used to enhance the activity of brain networks. However, it is unclear whether a combination of distinct NIBS approaches could enhance prefrontal cortical (PFC) activity., Objective: We propose to investigate the combined and standalone effects of two NIBS modalities on the PFC through a working memory task, single photon emission computed tomography (SPECT), and salivary cortisol. We hypothesize that the combined protocol will provoke greater changes in the collected measures compared to the remining protocols., Methods: A randomized, double-blind, sham-controlled, full-factorial design will be conducted. The effects of transcranial direct current stimulation (tDCS) and intermittent theta-burst stimulation (iTBS) will be investigated over four different sessions (sham tDCS + sham iTBS, anodal tDCS + sham iTBS, anodal tDCS + active iTBS and sham tDCS + active iTBS) in 30 healthy adult volunteers. A 99mTc-ethylene cysteine dimer (99mTC-ECD) will be administered during the NIBS session and neuroimaging will be acquired within one hour. Salivary cortisol will be collected before and after each session and an n-back working memory task will be applied after the end of each NIBS session. The outcomes will be cerebral perfusion alterations (99mTC-ECD SPECT), accuracy and reaction time in the n-back task, and changes in salivary cortisol level., Conclusion: The results from this trial can guide future therapeutic protocols for NIBS treatments stimulating the PFC by demonstrating that the combination of NIBS techniques is feasible, tolerable, and can lead to greater enhancement of PFC activity., Competing Interests: ARB is chief medical advisor of Flow™ and has a small equity holding in the company. No other conflicts of interest declared concerning the publication of this article.

Transcutaneous auricular vagus nerve stimulation (taVNS) has been proposed as a potential new tool in the treatment of major depressive disorder. Prior studies have demonstrated that taVNS enhances cognitive control and is able to modulate brain activity in key regions involved in cognitive emotion regulation, such as the anterior cingulate and medial prefrontal cortex, which is known to be impaired in depressed patients. Preclinical studies are lacking but may provide important insights into the working mechanisms of taVNS on cognitive emotion regulatory processes. In this between-subject study, 83 healthy subjects underwent a single-session of active taVNS or sham stimulation, after which cognitive reappraisal was examined using a computer-based cognitive emotion regulation task. Our results indicate that participants receiving active taVNS, compared to sham, were better at using cognitive reappraisal and rated their response to emotion-eliciting pictures as less intense. Yet, even though we found significant differences in behavioral measures of cognitive emotion regulation, no differences between groups were found in terms of physiological responses to the emotional stimuli. Overall, these findings suggest a positive effect of taVNS on the cognitive reappraisal of emotions, but future studies assessing objective measures of neural activity during cognitive emotion regulation following taVNS are warranted., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Social-evaluative threat (SET) - a situation in which one could be negatively evaluated by others - elicits profound (psycho)physiological reactivity which, if chronically present and not adaptively regulated, has deleterious effects on mental and physical health. Decreased self-awareness and increased other-awareness are understood to be an adaptive response to SET. Attentional deployment - the process of selectively attending to certain aspects of emotional stimuli to modulate emotional reactivity - is supported by fronto-parietal and fronto-limbic networks, with the dorsolateral prefrontal cortex being a central hub. The primary aim of the current study was to investigate the effects of active (versus sham) prefrontal transcranial direct current stimulation (tDCS) on self and other-attentional deployment during the exposure to a SET context. Seventy-four female participants received active or sham tDCS and were subsequently exposed to a rigged social feedback paradigm. In this paradigm a series of social evaluations were presented together with a photograph of the supposed evaluator and a self- photograph of the participant, while gaze behavior (time to first fixation, total fixation time) and skin conductance responses (SCRs; a marker of emotional reactivity) were measured. For half of the evaluations, participants could anticipate the valence (negative or positive) of the evaluation a priori . Analyses showed that participants receiving active tDCS were (a) slower to fixate on their self-photograph, (b) spent less time fixating on their self-photograph, and (c) spent more time fixating on the evaluator photograph. During unanticipated evaluations, active tDCS was associated with less time spent fixating on the evaluation. Furthermore, among those receiving active tDCS, SCRs were attenuated as a function of slower times to fixate on the self-photograph. Taken together, these results suggest that in a context of SET, prefrontal tDCS decreases self-attention while increasing other-attention, and that attenuated self-referential attention specifically may be a neurocognitive mechanism through which tDCS reduces emotional reactivity. Moreover, the results suggest that tDCS reduces vigilance toward stimuli that possibly convey threatening information, corroborating past research in this area., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Allaert, Erdogan, Sanchez-Lopez, Baeken, De Raedt and Vanderhasselt.)

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., (Copyright © 2021. Published by Elsevier B.V.)