Mental health during the COVID-19 pandemic and beyond: The importance of the vagus nerve for biopsychosocial resilience.

The COVID-19 pandemic has led to widespread increases in mental health problems, including anxiety and depression. The development of these and other psychiatric disorders may be related to changes in immune, endocrine, autonomic, cognitive, and affective processes induced by a SARS-CoV-2 infection. Interestingly, many of these same changes can be triggered by psychosocial stressors such as social isolation and rejection, which have become increasingly common due to public policies aimed at reducing the spread of SARS-CoV-2. The present review aims to shed light on these issues by describing how viral infections and stress affect mental health. First, we describe the multi-level mechanisms linking viral infection and life stress exposure with risk for psychopathology. Then, we summarize how resilience can be enhanced by targeting vagus nerve function by, for example, applying transcutaneous vagus nerve stimulation and targeting lifestyle factors, such as exercise. With these biopsychosocial insights in mind, researchers and healthcare professionals will be better equipped to reduce risk for psychopathology and increase resilience during this challenging pandemic period and beyond.

Combined transcranial direct current stimulation and psychological interventions: State of the art and promising perspectives for clinical psychology.

Recent literature shows great heterogeneity in the reported efficacy of transcranial direct current stimulation (tDCS) as a stand-alone psychiatric treatment. Aiming to increase its efficacy, tDCS has been combined with psychological interventions. Our state-of-the-art overview of such combined treatment trials indicates, however, that these usually do not elicit synergistic clinical effects. We therefore explored more basic mechanisms related to the brain state-dependency of tDCS. Importantly, based on our overview, the efficacy of combined interventions may depend on whether individual patients present with endophenotypes that are implicated in the development and maintenance of psychopathology, such as prefrontal-mediated cognitive dysfunction. We discuss how future studies may contribute to the development of personally-tailored dual active treatments by adhering to the Research Domain Criteria (RDoC) framework. RDoC-based mechanistic research may reveal alternative neural circuits that should be functionally targeted by both tDCS and psychological interventions, with promising avenues for clinical psychological science and practice.

Prefrontal TDCS attenuates medial prefrontal connectivity upon being criticized in individuals scoring high on perceived criticism.

The mechanisms by which transcranial direct current stimulation (tDCS) influences emotional processing - and whether this is related to individual vulnerability for psychopathology - are still poorly understood. The present study aimed to investigate if one prefrontal tDCS session modulates mood and neural functional connectivity after being exposed to negative information differently in individuals low or high in perceived criticism (PC), which has been related to vulnerability for psychiatric illness. In a randomized cross-over design, one session of MRI-compatible prefrontal tDCS (neuronavigated placement of the anodal electrode at the left dorsolateral prefrontal cortex and the cathodal electrode at the right supraorbital region; vs. sham) was administered to healthy females, prior to listening to self-referential criticism. PC-dependent (low vs. high PC) changes in mood and resting-state functional connectivity patterns following tDCS and after hearing criticism were explored. After being criticized all females (low and high PC) felt angrier and more depressed, both in the active tDCS or sham tDCS condition. However, in contrast to low PC females, in high PC females prefrontal tDCS reduced connectivity between the left dorsal anterior cingulate cortex and the right dorsomedial prefrontal cortex following criticism. Despite having no differential effects on self-reported mood, prefrontal tDCS reduces medial prefrontal neural connectivity after being criticized in high PC females compared to low PC females. Depending on individual vulnerability for psychopathology, a single tDCS session differentially affects neural processing of negative emotional information, especially in brain regions involved in monitoring, experiencing and appraising/evaluating emotional material.

One MRI-compatible tDCS session attenuates ventromedial cortical perfusion when exposed to verbal criticism: The role of perceived criticism.

Transcranial direct current stimulation (tDCS) is a potential treatment strategy for mood and anxiety disorders, but how this application may influence emotional processes, and whether this is related to individual characteristics, is not well understood. It has been proposed that perceived criticism (PC) may represent a vulnerability factor for the development of such mental illnesses. To decipher whether neural mechanisms of action of tDCS potentially differ depending on PC status (low vs. high), we evaluated mood and brain perfusion before and after applying MRI-compatible tDCS, and after participants were exposed to verbal criticism in the scanner. Experimental design 30 healthy nondepressed females were included in a sham-controlled crossover MRI-compatible tDCS study. Brain perfusion was measured by means of arterial spin labeling (ASL) before and after tDCS applied to the left dorsolateral prefrontal cortex (DLPFC), and after hearing criticism. Before the experiment, all participants provided a rating of PC in their closest environment. Principal observations at the behavioral level, criticism made participants angrier. This was unrelated to the active or sham stimulation. After being criticized, females scoring high on PC had significantly decreased brain perfusion in the pregenual anterior cingulate cortex (pgACC) and medioprefrontal cortex (mPFC), after active tDCS but not sham. The decrease in pgACC/mPFC perfusion points to a significant impact of tDCS in brain areas related to stress responses and self-referential processes, especially in females scoring high on PC, which has been shown to be related to vulnerability for mood and anxiety disorders.

Left prefrontal neuronavigated electrode localization in tDCS: 10-20 EEG system versus MRI-guided neuronavigation.

Transcranial direct current stimulation (tDCS) involves positioning two electrodes at specifically targeted locations on the human scalp. In neuropsychiatric research, the anode is often placed over the left dorsolateral prefrontal cortex (DLPFC), while the cathode is positioned over a contralateral cephalic region above the eye, referred-to as the supraorbital region. Although the 10-20 EEG system is frequently used to locate the DLPFC, due to inter-subject brain variability, this method may lack accuracy. Therefore, we compared in forty participants left DLPFC-localization via the 10-20 EEG system to MRI-guided neuronavigation. In one participant, with individual electrode positions in close proximity to the mean electrode position across subjects, we also investigated whether distinct electrode localizations were associated with different tDCS-induced electrical field distributions. Furthermore, we aimed to examine which neural region is targeted when placing the reference-electrode on the right supraorbital region. Compared to the 10-20 EEG system, MRI-guided neuronavigation localizes the DLPFC-targeting anode more latero-posteriorly, targeting the middle prefrontal gyrus. tDCS-induced electric fields (n = 1) suggest that both localization methods induce significantly different electric fields in distinct brain regions. Considering the frequent application of tDCS as a neuropsychiatric treatment, an evaluation and direct comparison of the clinical efficacy of targeting methods is warranted.

The effect of the interval-between-sessions on prefrontal transcranial direct current stimulation (tDCS) on cognitive outcomes: a systematic review and meta-analysis.

Recently, there has been wide interest in the effects of transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC) on cognitive functioning. However, many methodological questions remain unanswered. One of them is whether the time interval between active and sham-controlled stimulation sessions, i.e. the interval between sessions (IBS), influences DLPFC tDCS effects on cognitive functioning. Therefore, a systematic review and meta-analysis was performed of experimental studies published in PubMed, Science Direct, and other databases from the first data available to February 2016. Single session sham-controlled within-subject studies reporting the effects of tDCS of the DLPFC on cognitive functioning in healthy controls and neuropsychiatric patients were included. Cognitive tasks were categorized in tasks assessing memory, attention, and executive functioning. Evaluation of 188 trials showed that anodal vs. sham tDCS significantly decreased response times and increased accuracy, and specifically for the executive functioning tasks, in a sample of healthy participants and neuropsychiatric patients (although a slightly different pattern of improvement was found in analyses for both samples separately). The effects of cathodal vs. sham tDCS (45 trials), on the other hand, were not significant. IBS ranged from less than 1 h to up to 1 week (i.e. cathodal tDCS) or 2 weeks (i.e. anodal tDCS). This IBS length had no influence on the estimated effect size when performing a meta-regression of IBS on reaction time and accuracy outcomes in all three cognitive categories, both for anodal and cathodal stimulation. Practical recommendations and limitations of the study are further discussed.

A Systematic Review and Meta-Analysis of the Effects of Transcranial Direct Current Stimulation (tDCS) Over the Dorsolateral Prefrontal Cortex in Healthy and Neuropsychiatric Samples: Influence of Stimulation Parameters.

BACKGROUND: Research into the effects of transcranial direct current stimulation of the dorsolateral prefrontal cortex on cognitive functioning is increasing rapidly. However, methodological heterogeneity in prefrontal tDCS research is also increasing, particularly in technical stimulation parameters that might influence tDCS effects. OBJECTIVE: To systematically examine the influence of technical stimulation parameters on DLPFC-tDCS effects. METHODS: We performed a systematic review and meta-analysis of tDCS studies targeting the DLPFC published from the first data available to February 2016. Only single-session, sham-controlled, within-subject studies reporting the effects of tDCS on cognition in healthy controls and neuropsychiatric patients were included. RESULTS: Evaluation of 61 studies showed that after single-session a-tDCS, but not c-tDCS, participants responded faster and more accurately on cognitive tasks. Sub-analyses specified that following a-tDCS, healthy subjects responded faster, while neuropsychiatric patients responded more accurately. Importantly, different stimulation parameters affected a-tDCS effects, but not c-tDCS effects, on accuracy in healthy samples vs. PATIENTS: increased current density and density charge resulted in improved accuracy in healthy samples, most prominently in females; for neuropsychiatric patients, task performance during a-tDCS resulted in stronger increases in accuracy rates compared to task performance following a-tDCS. CONCLUSIONS: Healthy participants respond faster, but not more accurate on cognitive tasks after a-tDCS. However, increasing the current density and/or charge might be able to enhance response accuracy, particularly in females. In contrast, online task performance leads to greater increases in response accuracy than offline task performance in neuropsychiatric patients. Possible implications and practical recommendations are discussed.

Accelerated intermittent theta burst stimulation treatment in medication-resistant major depression: A fast road to remission?

Although accelerated repetitive Transcranial Magnetic Stimulation (rTMS) paradigms and intermittent Theta-burst Stimulation (iTBS) may have the potency to result in superior clinical outcomes in Treatment Resistant Depression (TRD), accelerated iTBS treatment has not yet been studied. In this registered randomized double-blind sham-controlled crossover study, spread over four successive days, 50 TRD patients received 20 iTBS sessions applied to the left dorsolateral prefrontal cortex (DLPFC). The accelerated iTBS treatment procedure was found to be safe and resulted in immediate statistically significant decreases in depressive symptoms regardless of order/type of stimulation (real/sham). While only 28% of the patients showed a 50% reduction of their initial Hamilton Depression Rating Scale score at the end of the two-week procedure, this response rate increased to 38% when assessed two weeks after the end of the sham-controlled iTBS protocol, indicating delayed clinical effects. Importantly, 30% of the responders were considered in clinical remission. We found no demographic predictors for response. Our findings indicate that only four days of accelerated iTBS treatment applied to the left DLPFC in TRD may lead to meaningful clinical responses within two weeks post stimulation.