Network-targeted transcranial direct current stimulation of the hypothalamus appetite-control network: a feasibility study.

The hypothalamus is the key regulator for energy homeostasis and is functionally connected to striatal and cortical regions vital for the inhibitory control of appetite. Hence, the ability to non-invasively modulate the hypothalamus network could open new ways for the treatment of metabolic diseases. Here, we tested a novel method for network-targeted transcranial direct current stimulation (net-tDCS) to influence the excitability of brain regions involved in the control of appetite. Based on the resting-state functional connectivity map of the hypothalamus, a 12-channel net-tDCS protocol was generated (Neuroelectrics Starstim system), which included anodal, cathodal and sham stimulation. Ten participants with overweight or obesity were enrolled in a sham-controlled, crossover study. During stimulation or sham control, participants completed a stop-signal task to measure inhibitory control. Overall, stimulation was well tolerated. Anodal net-tDCS resulted in faster stop signal reaction time (SSRT) compared to sham (p = 0.039) and cathodal net-tDCS (p = 0.042). Baseline functional connectivity of the target network correlated with SSRT after anodal compared to sham stimulation (p = 0.016). These preliminary data indicate that modulating hypothalamus functional network connectivity via net-tDCS may result in improved inhibitory control. Further studies need to evaluate the effects on eating behavior and metabolism.

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

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

Neurocognitive function as outcome and predictor for prefrontal transcranial direct current stimulation in major depressive disorder: an analysis from the DepressionDC trial.

Transcranial direct current stimulation (tDCS) of the prefrontal cortex might beneficially influence neurocognitive dysfunctions associated with major depressive disorder (MDD). However, previous studies of neurocognitive effects of tDCS have been inconclusive. In the current study, we analyzed longitudinal, neurocognitive data from 101 participants of a randomized controlled multicenter trial (DepressionDC), investigating the efficacy of bifrontal tDCS (2 mA, 30 min/d, for 6 weeks) in patients with MDD and insufficient response to selective serotonin reuptake inhibitors (SSRI). We assessed whether active tDCS compared to sham tDCS elicited beneficial effects across the domains of memory span, working memory, selective attention, sustained attention, executive process, and processing speed, assessed with a validated, digital test battery. Additionally, we explored whether baseline cognitive performance, as a proxy of fronto-parietal-network functioning, predicts the antidepressant effects of active tDCS versus sham tDCS. We found no statistically significant group differences in the change of neurocognitive performance between active and sham tDCS. Furthermore, baseline cognitive performance did not predict the clinical response to tDCS. Our findings indicate no advantage in neurocognition due to active tDCS in MDD. Additional research is required to systematically investigate the effects of tDCS protocols on neurocognitive performance in patients with MDD.

Treatment of adult attention-deficit hyperactivity disorder (ADHD) with transcranial direct current stimulation (tDCS): study protocol for a parallel, randomized, double-blinded, sham-controlled, multicenter trial (Stim-ADHD).

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation treatment used as an alternative or complementary treatment for various neuropsychiatric disorders, and could be an alternative or add-on therapy to psychostimulants in attention-deficit hyperactivity disorder (ADHD). Previous studies provided some evidence for improvements in cognition and clinical symptoms in pediatric and adult ADHD patients. However, data from multi-center randomized controlled trials (RCTs) for this condition are lacking. Thus, our aim is to evaluate short- and mid-term effects of tDCS in this multi-center, randomized, double blind, and sham-controlled, parallel group clinical trial with a 1:1 randomization ratio. Primary endpoint is the total score of DSM-IV scale of the internationally established Conners' Adult ADHD Rating Scales (German self-report screening version, CAARS-S-SR), at day 14 post-intervention (p.i.) to detect short-term lasting effects analyzed via analyses of covariance (ANCOVAs). In case of significant between-groups differences at day 14 p.i., hierarchically ordered hypotheses on mid-term lasting effects will be investigated by linear mixed models with visit (5 time points), treatment, treatment by visit interaction, and covariates as fixed categorical effects plus a patient-specific visit random effect, using an unstructured covariance structure to model the residual within-patient errors. Positive results of this clinical trial will expand the treatment options for adult ADHD patients with tDCS and provide an alternative or add-on therapy to psychostimulants with a low risk for side effects.Trial Registration The trial was registered on July 29, 2022 in the German Clinical Trials Register (DRKS00028148).

Theta burst stimulation add on to dialectical behavioral therapy in borderline-personality-disorder: methods and design of a randomized, single-blind, placebo-controlled pilot trial.

Specialized psychotherapeutic treatments like dialectical behavioral therapy (DBT) are recommended as first treatment for borderline personality disorder (BPD). In recent years, studies have emerged that focus on repetitive transcranial magnetic stimulation (rTMS) in BPD. Both have independently demonstrated efficacy in the treatment of BPD. Intermitted theta burst stimulation (iTBS), a modified design of rTMS, is thought to increase the excitability of neurons and could be a supplement to psychotherapy in addition to being a standalone treatment. However, no studies to date have investigated the combination of DBT and rTMS/iTBS. This study protocol describes the methods and design of a randomized, single-blinded, sham-controlled clinical pilot study in which BPD patients will be randomly assigned to either iTBS or sham during four consecutive weeks (20 sessions in total) in addition to standardized DBT treatment. The stimulation will focus on the unilateral stimulation of the left dorsolateral prefrontal cortex (DLPFC), which plays an important role in the control of impulsivity and risk-taking. Primary outcome is the difference in borderline symptomatology, while secondary target criteria are depressive symptoms, general functional level, impulsivity and self-compassion. Statistical analysis of therapy response will be conducted by Mixed Model Repeated Measurement using a 2 × 2-factorial between-subjects design with the between-subject factor stimulation (TMS vs. Sham) and the within-subject factor time (T0 vs. T1). Furthermore, structural magnetic resonance imaging (MRI) will be conducted and analyzed. The study will provide evidence and insight on whether iTBS has an enhancing effect as add-on to DBT in BPD.Trial registration: drks.de (DRKS00020413) registered 13/01/2020.

tDCS effects in basic symbolic number magnitude processing are not significantly lateralized.

Functional lateralization was previously established for various cognitive domains-but not for number processing. Although numbers are considered to be bilaterally represented in the intraparietal sulcus (IPS), there are some indications of different functional roles of the left vs. right IPS in processing number pairs with small vs. large distance, respectively. This raises the question whether number size plays a distinct role in the lateralization within the IPS. In our preregistered study, we applied anodal transcranial direct current stimulation (tDCS) over the left vs. right IPS to investigate the effect of stimulation as compared to sham on small vs. large distance, in both single-digit and two-digit number comparison. We expected that anodal tDCS over the left IPS facilitates number comparison with small distance, while anodal tDCS over the right IPS facilitates number comparison with large distance. Results indicated no effect of stimulation; however, exploratory analyses revealed that tDCS over the right IPS slowed down single-digit number processing after controlling for the training effect. In conclusion, number magnitude processing might be bilaterally represented in the IPS, however, our exploratory analyses emphasise the need for further investigation on functional lateralization of number processing.

Sex matters for the enhancement of cognitive training with transcranial direct current stimulation (tDCS).

BACKGROUND: Transcranial direct current stimulation (tDCS) can influence brain network activity and associated cognitive and behavioural functions. In addition to the extensive variety in stimulation parameters, numerous biological factors drive these effects, however these are yet poorly understood. Here, we investigate one of the major biological factors by focusing on sex-dependent effects of tDCS on a challenging cognitive control task (adaptive paced auditory serial addition task [PASAT]) in healthy humans. METHODS: This sex-specific re-analysis was performed on data of 163 subjects who underwent a 2-week cognitive control training (6 sessions in total). Subjects received either verum (anodal/cathodal) or sham tDCS. Electrodes were placed over the left or right dorsolateral prefrontal cortex and the respective contralateral deltoid muscle. Cognitive control was measured as performance in the PASAT and was analysed in respect to stimulation conditions (sham, anodal, cathodal) and sex. RESULTS: Regardless of stimulation condition, performance gains between the sexes were higher in females compared to males (p = 0.0038). Female's performance during anodal tDCS exceeded male's (p = 0.0070), yet no effects were found for cathodal or sham tDCS. Moreover, in females we found a superior effect for anodal tDCS over sham stimulation (fanodal: p = 0.0354; fcathodal: p = 0.6181), but no such effect in males (manodal: p = 0.6882; mcathodal: p = 0.4822). CONCLUSIONS: This study highlights the relevance of biological sex for the effects of tDCS on cognitive training. Thus, an increased attention to biological sex is advisable in future brain stimulation research to highlight and in consequence better understand potentially underlying sex-specific mechanisms. Considering biological sex will further advance customisation and individualisation of tDCS interventions. Trial registration ClinicalTrials.gov, NCT04108663.

In previous studies, brain stimulation techniques like transcranial direct current stimulation (tDCS) have been shown to support cognitive trainings. However, these effects are rather small and vary between people. A key factor of variability is the biological sex. Hence, in this study we were interested in whether the effects of tDCS differ between females and males. To answer this research question, we analysed the data of 163 human subjects who underwent a 2-week cognitive control training program, which incorporates a challenging cognitive task (the adaptive paced auditory serial addition task [PASAT]). During the PASAT, subjects have to solve a stressful calculation exercise. Concurrently to solving this task, the subjects received either real (further divided into anodal [= enhancing] and cathodal [= inhibiting]) or placebo tDCS. We found that females had greater performance gains in the task than males, regardless of the type of tDCS they received. Furthermore, females performed particularly well when they received anodal tDCS, but there were no significant effects for cathodal or placebo tDCS. For males, we did not find any significant benefits of tDCS. These findings highlight the importance of considering biological sex in future brain stimulation research and suggest that biological sex is an important component to consider when studying the effects of tDCS. By paying more attention to this factor, researchers can better understand how tDCS works and develop more effective and personalised interventions.

Transcranial direct current stimulation as an additional treatment to selective serotonin reuptake inhibitors in adults with major depressive disorder in Germany (DepressionDC): a triple-blind, randomised, sham-controlled, multicentre trial.

BACKGROUND: Transcranial direct current stimulation (tDCS) has been proposed as a feasible treatment for major depressive disorder (MDD). However, meta-analytic evidence is heterogenous and data from multicentre trials are scarce. We aimed to assess the efficacy of tDCS versus sham stimulation as an additional treatment to a stable dose of selective serotonin reuptake inhibitors (SSRIs) in adults with MDD. METHODS: The DepressionDC trial was triple-blind, randomised, and sham-controlled and conducted at eight hospitals in Germany. Patients being treated at a participating hospital aged 18-65 years were eligible if they had a diagnosis of MDD, a score of at least 15 on the Hamilton Depression Rating Scale (21-item version), no response to at least one antidepressant trial in their current depressive episode, and treatment with an SSRI at a stable dose for at least 4 weeks before inclusion; the SSRI was continued at the same dose during stimulation. Patients were allocated (1:1) by fixed-blocked randomisation to receive either 30 min of 2 mA bifrontal tDCS every weekday for 4 weeks, then two tDCS sessions per week for 2 weeks, or sham stimulation at the same intervals. Randomisation was stratified by site and baseline Montgomery-Åsberg Depression Rating Scale (MADRS) score (ie, <31 or ≥31). Participants, raters, and operators were masked to treatment assignment. The primary outcome was change on the MADRS at week 6, analysed in the intention-to-treat population. Safety was assessed in all patients who received at least one treatment session. The trial was registered with ClinicalTrials.gov (NCT02530164). FINDINGS: Between Jan 19, 2016, and June 15, 2020, 3601 individuals were assessed for eligibility. 160 patients were included and randomly assigned to receive either active tDCS (n=83) or sham tDCS (n=77). Six patients withdrew consent and four patients were found to have been wrongly included, so data from 150 patients were analysed (89 [59%] were female and 61 [41%] were male). No intergroup difference was found in mean improvement on the MADRS at week 6 between the active tDCS group (n=77; -8·2, SD 7·2) and the sham tDCS group (n=73; -8·0, 9·3; difference 0·3 [95% CI -2·4 to 2·9]). Significantly more participants had one or more mild adverse events in the active tDCS group (50 [60%] of 83) than in the sham tDCS group (33 [43%] of 77; p=0·028). INTERPRETATION: Active tDCS was not superior to sham stimulation during a 6-week period. Our trial does not support the efficacy of tDCS as an additional treatment to SSRIs in adults with MDD. FUNDING: German Federal Ministry of Education and Research.

Behavioural biases in the interaction with food objects in virtual reality and its clinical implication for binge eating disorder.

Cognitive processes play a central role in the development, maintenance and remission in mental disorders, like in Binge Eating Disorder (BED). Insights into cognitive mechanisms reflected by embodied interaction with food and its connections to clinically relevant psychopathology offer new possibilities for translational diagnostics and interventions. We longitudinally investigated the manual interaction with food in a virtual reality (VR) in 31 patients with BED. Patients were assessed at baseline before participating in a randomized-controlled trial (RCT) investigating a computer-based inhibitory control training programme enhanced by transcranial direct current stimulation (tDCS) and at a 6-week follow-up. At both assessments, an experimental VR paradigm was conducted and patients were characterized concerning eating disorder psychopathology, eating behaviour, general impulsivity and food craving. In the experimental task, one of two simultaneously presented objects (food vs. office tools) had to be collected. Food was recognized faster than office tools and subsequent approach behaviour was initiated faster, whereas thereafter, food was collected slower than office tools. Exploratory, we could not find a modulatory effect of applied tDCS on the interaction with food. No relationship between behavioural biases and sample characterizations could be detected. Two different stages in the manual interaction with food were found: a faster first stage that comprises recognition and movement initiation and a slower second stage that comprises controlled handling and may reflect aversive motivational processes. As the behavioural patterns do not change with an ameliorated BED-psychopathology at the second assessment, the task seems insensitive in detecting translational interconnections between behavioural biases and BED-characteristics.Level of evidence: Level I, experimental study.

Inhibitory Control Training Enhanced by Transcranial Direct Current Stimulation to Reduce Binge Eating Episodes: Findings from the Randomized Phase II ACCElect Trial.

INTRODUCTION: Binge eating disorder (BED) is characterized by recurrent binge eating (BE) episodes with loss of control. Inhibitory control impairments, including alterations in dorsolateral prefrontal cortex (dlPFC) functioning, have been described for BED. A targeted modulation of inhibitory control circuits by the combination of inhibitory control training and transcranial brain stimulation could be promising. OBJECTIVE: The aim of the study was to demonstrate feasibility and clinical effects of a transcranial direct current stimulation (tDCS)-enhanced inhibitory control training to reduce BE episodes and to generate an empirical basis for a confirmatory trial. METHODS: We performed a monocentric clinical phase II double-blind randomized trial with two parallel arms. Forty-one adult outpatients with full-syndrome BED according to DSM-5 received six sessions of food-related inhibitory control training, randomly combined with 2 mA verum or sham tDCS of the right dlPFC. The main outcome was BE frequency within a 4-week interval after treatment termination (T8; primary) and at 12-week follow-up (T9; secondary) as compared to baseline. RESULTS: BE frequency was reduced in the sham group from 15.5 to 5.9 (T8) and to 6.8 (T9); in the verum group, the reduction was 18.6 to 4.4 (T8) resp. 3.8 (T9). Poisson regression with the study arm as the factor and baseline BE frequency as the covariate revealed a p value of 0.34 for T8 and 0.026 for T9. Sham and real tDCS differed at T9 in BE frequency. CONCLUSIONS: Inhibitory control training enhanced by tDCS is safe in patients with BED and results in a substantial and sustainable reduction in BE frequency which unfolds over several weeks post-treatment. These results constitute the empirical basis for a confirmatory trial.

Motor cortical excitability and pre-supplementary motor area neurochemistry in healthy adults with substantia nigra hyperechogenicity.

Substantia nigra (SN) hyperechogenicity, viewed with transcranial ultrasound, is a risk marker for Parkinson's disease. We hypothesized that SN hyperechogenicity in healthy adults aged 50-70 years is associated with reduced short-interval intracortical inhibition in primary motor cortex, and that the reduced intracortical inhibition is associated with neurochemical markers of activity in the pre-supplementary motor area (pre-SMA). Short-interval intracortical inhibition and intracortical facilitation in primary motor cortex was assessed with paired-pulse transcranial magnetic stimulation in 23 healthy adults with normal (n = 14; 61 ± 7 yrs) or abnormally enlarged (hyperechogenic; n = 9; 60 ± 6 yrs) area of SN echogenicity. Thirteen of these participants (7 SN- and 6 SN+) also underwent brain magnetic resonance spectroscopy to investigate pre-SMA neurochemistry. There was no relationship between area of SN echogenicity and short-interval intracortical inhibition in the ipsilateral primary motor cortex. There was a significant positive relationship, however, between area of echogenicity in the right SN and the magnitude of intracortical facilitation in the right (ipsilateral) primary motor cortex (p = .005; multivariate regression), evidenced by the amplitude of the conditioned motor evoked potential (MEP) at the 10-12 ms interstimulus interval. This relationship was not present on the left side. Pre-SMA glutamate did not predict primary motor cortex inhibition or facilitation. The results suggest that SN hyperechogenicity in healthy older adults may be associated with changes in excitability of motor cortical circuitry. The results advance understanding of brain changes in healthy older adults at risk of Parkinson's disease.

Gamification improves antidepressant effects of cognitive control training-A pilot trial.

Objective: Computerised cognitive trainings have been put forward to improve control over negatively biased information processing and associated depressive symptomatology. Yet, disease-related impairments of motivation and endurance, as well as insufficient accessibility hinder use of this promising therapeutic opportunity. Here, we developed an app (de:)press© ) that utilizes a cognitive control training (paced auditory serial addition task) enriched with gamification and information elements. We compared a six-week training with de:)press© to a non-gamified version (active control group). Methods: Thirty-two depressed participants were included. Each received either de:)press© or the non-gamified version and was instructed to train three times per week for two weeks. Afterwards (four weeks) they were free to train at their own discretion. Depression severity was assessed during training and two follow-up sessions. Primary endpoint was defined as difference between groups [change of Montgomery-Åsberg Depression Rating Scale (MADRS)] four weeks after end of training. Results: Depression severity decreased in both groups. At primary endpoint, MADRS scores were significantly lower in the de:)press© -group compared to the control group. No differences were observed at three months' follow-up. Intervention usability was consistently rated positively. Participants who had trained with de:)press© maintained the recommended training frequency without further prompting. Besides transient fatigue or frustration, no adverse effects were observed. Conclusion: This pilot demonstrates that gamification and information elements can substantially increase cognitive control training efficacy in alleviating depressive symptoms. Moreover, it provides first evidence for the feasibility and efficacy of de:)press© as an add-on intervention to treat depression. Clinical trial registration: The study is registered under ClinicalTrials.gov, identifier: NCT04400162.

Implicit measures of alcohol approach and drinking identity in alcohol use disorder: A preregistered double-blind randomized trial with cathodal transcranial direct current stimulation (tDCS).

Alcohol use disorder (AUD) is a severe and widespread mental disorder with a huge negative impact on the social, economic and health dimensions. The identification of risk factors for the development of AUD and for relapse in existing AUD are crucial for prevention and treatment approaches. Alcohol-related implicit associations have been shown to contribute to drinking and might partially explain sudden relapses. The aims of this study are to investigate implicit associations in abstinent AUD patients and to test whether cathodal transcranial direct current stimulation (tDCS) modulates implicit associations. We measured performance in two alcohol-related implicit association tests (IATs) and two control tasks (flower-insect IAT, Stroop task) in 27 abstinent AUD patients with 31.5 (SD = 36) days of abstinence on average. During the execution of the tasks, we applied 1 mA cathodal or sham tDCS over the left dorsolateral prefrontal cortex (dlPFC) in a sham-controlled within-subject design. Results show an implicit bias of alcohol avoidance and implicit nondrinking identity for abstinent AUD patients. Cathodal tDCS modulated neither alcohol-related implicit associations nor the control tasks. This study complements knowledge about implicit alcohol-related association in AUD patients and shows no effect of a neuromodulatory intervention to alter implicit associations with the present parameters.

Efficacy of Augmentation of Cognitive Behavioral Therapy With Transcranial Direct Current Stimulation for Depression: A Randomized Clinical Trial.

Importance: Major depressive disorder (MDD) affects approximately 10% of the population globally. Approximately 20% to 30% of patients with MDD do not sufficiently respond to standard treatment. Therefore, there is a need to develop more effective treatment strategies. Objective: To investigate whether the efficacy of cognitive behavioral therapy (CBT) for the treatment of MDD can be enhanced by concurrent transcranial direct current stimulation (tDCS). Design, Setting, and Participants: The double-blind, placebo-controlled randomized clinical trial PsychotherapyPlus was conducted at 6 university hospitals across Germany. Enrollment took place between June 2, 2016, and March 10, 2020; follow-up was completed August 27, 2020. Adults aged 20 to 65 years with a single or recurrent depressive episode were eligible. They were either not receiving medication or were receiving a stable regimen of antidepressant medication (selective serotonin reuptake inhibitor and/or mirtazapine). A total of 148 women and men underwent randomization: 53 individuals were assigned to CBT alone (group 0), 48 to CBT plus tDCS (group 1), and 47 to CBT plus sham-tDCS (group 2). Interventions: Participants attended a 6-week group intervention comprising 12 sessions of CBT. If assigned, tDCS was applied simultaneously. Active tDCS included stimulation with an intensity of 2 mA for 30 minutes (anode over F3, cathode over F4). Main Outcomes and Measures: The primary outcome was the change in Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline to posttreatment in the intention-to-treat sample. Scores of 0 to 6 indicate no depression; 7 to 19, mild depression; 20 to 34, moderate depression; and 34 and higher, severe depression. Results: A total of 148 patients (89 women, 59 men; mean [SD] age, 41.1 [13.7] years; MADRS score at baseline, 23.0 [6.4]) were randomized. Of these, 126 patients (mean [SD] age, 41.5 [14.0] years; MADRS score at baseline, 23.0 [6.3]) completed the study. In each of the intervention groups, intervention was able to reduce MADRS scores by a mean of 6.5 points (95% CI, 3.82-9.14 points). The Cohen d value was -0.90 (95% CI, -1.43 to -0.50), indicating a significant effect over time. However, there was no significant effect of group and no significant interaction of group × time, indicating the estimated additive effects were not statistically significant. There were no severe adverse events throughout the whole trial, and there were no significant differences of self-reported adverse effects during and after stimulation between groups 1 and 2. Conclusions and Relevance: Based on MADRS score changes, this trial did not indicate superior efficacy of tDCS-enhanced CBT compared with 2 CBT control conditions. The study confirmed that concurrent group CBT and tDCS is safe and feasible. However, additional research on mechanisms of neuromodulation to complement CBT and other behavioral interventions is needed. Trial Registration: ClinicalTrials.gov Identifier: NCT02633449.

Ameliorating cognitive control in patients with binge eating disorder by electrical brain stimulation: study protocol of the randomized controlled ACCElect pilot trial.

BACKGROUND: The current first-line treatment for binge eating disorder (BED), which is psychotherapy, is moderately effective in terms of abstinence from binge-eating. Neurobiological evidence suggests that people affected by BED show difficulties along the spectrum of impulsivity, including inhibitory control impairments and highlights the potential of novel treatment approaches directly targeting inhibitory control, including cognitive training approaches and non-invasive brain stimulation. METHODS: ACCElect is a prospective, randomized controlled pilot trial investigating a novel, food-related inhibitory control training combined with transcranial direct current stimulation (tDCS). 40 patients with BED will be randomly assigned to receive the training either combined with verum or with sham stimulation (control condition). The inhibitory control training is based on principles of the antisaccade paradigm and comprises six training sessions over two weeks. Core aims are the investigation of feasibility and clinically relevant effects of a tDCS-enhanced inhibitory control training in BED patients and the establishment of a data basis for a larger efficacy trial. The primary clinical endpoint is binge-eating (BE) frequency in terms of changes in BE episodes four weeks after treatment termination as compared to baseline. Key secondary outcomes comprise ED pathology and general psychopathology, inhibitory control capacities, quality of life as well as acceptability and satisfaction with the intervention. DISCUSSION: The results of the present trial will contribute to the development of novel neurobiologically informed treatment approaches for patients suffering from BED. Trial registration The ACCElect trial was prospectively registered on October 1, 2020, under the registration number NCT04572087 at ClinicalTrials.gov ( https://clinicaltrials.gov/ct2/show/NCT04572087 ).

[Non-Invasive Brain Stimulation in Psychiatric Disorders]. / Nichtinvasive Hirnstimulationsverfahren in der Psychiatrie.

Based on neurophysiological findings, non-invasive brain stimulation methods offer an integrative treatment approach for mental disorders. Some of the stimulation methods have already been extensively studied for specific psychiatric indications and have become established as reasonable treatment option. For example, transcranial magnetic stimulation (TMS) for the treatment of refractory depression received approval from the Food and Drug Administration (FDA) in the United States in 2008. However, in Europe and especially in Germany, TMS is not widely offered even in a university setting. The following article describes the available technologies and their biological mechanisms of action, outlines the clinical indication and application of TMS, and summarizes the clinical evidence. The article is based on recently published guidelines for the therapeutic use of non-invasive brain stimulation 1 2 3.

Investigating mechanisms of cognitive control training: neural signatures of PASAT performance in depressed patients.

Major depression disorder (MDD) is characterized by cognitive control (CC) dysfunctions associated with increased attention toward negative information. The paced auditory serial addition task (PASAT) has been used as a targeted training of CC and studies show promising effects on depressive symptoms. However, neural mechanisms underlying its efficacy are still unclear. Based on previous findings of feedback-locked event-related potentials in healthy subjects, we investigated neural signatures during PASAT performance in 46 depressed patients. We found significantly larger amplitudes after negative than positive feedback for the P300 and late positive potential (LPP). However, this difference was not significant for the feedback-related negativity (FRN). Moreover, no associations of valence-specific ERPs and PASAT performance nor depressive symptoms were found. This indicates that depressed patients seem unable to use neural activation in late feedback processing stages (P300, LPP) to adapt accordingly. Moreover, lack of valence-specific neural reaction in early feedback processing stages (FRN) might point toward emotional indifference in depressed patients.Trial registration number: NCT03518749 Date of registration: May 8, 2018.

Dynamic DNA Methylation Changes in the COMT Gene Promoter Region in Response to Mental Stress and Its Modulation by Transcranial Direct Current Stimulation.

Changes in epigenetic modifications present a mechanism how environmental factors, such as the experience of stress, can alter gene regulation. While stress-related disorders have consistently been associated with differential DNA methylation, little is known about the time scale in which these alterations emerge. We investigated dynamic DNA methylation changes in whole blood of 42 healthy male individuals in response to a stressful cognitive task, its association with concentration changes in cortisol, and its modulation by transcranial direct current stimulation (tDCS). We observed a continuous increase in COMT promotor DNA methylation which correlated with higher saliva cortisol levels and was still detectable one week later. However, this lasting effect was suppressed by concurrent activity-enhancing anodal tDCS to the dorsolateral prefrontal cortex. Our findings support the significance of gene-specific DNA methylation in whole blood as potential biomarkers for stress-related effects. Moreover, they suggest alternative molecular mechanisms possibly involved in lasting behavioral effects of tDCS.

A Pilot Event-Related Potentials Study on Mechanisms Underlying a tDCS-Enhanced Food-Specific Response Inhibition Task for Patients With Binge Eating Disorder.

Behavioural studies demonstrate alterations in cognitive functioning, particularly impaired response inhibition and increased attentional bias towards food in binge eating disorder (BED). This pilot study aimed to investigate the neurophysiological processing of a food-specific inhibition training combined with anodal transcranial direct current stimulation (tDCS) of the right dorsolateral prefrontal cortex (DLPFC) in 16 patients with BED (mean age = 38.6, mean BMI = 33.7 kg/m2). Patients performed a food-specific antisaccade task at baseline (T0) and in a cross-over design with verum vs. sham stimulation at T1 and T2. We investigated (i) event-related potentials (ERPs; N2, ERN and P3 amplitudes) while executing the task at baseline, (ii) whether baseline ERPs would predict task performance at T1 and T2 and (iii) associations between ERPs, eating disorder pathology and impulsivity at baseline. The mean amplitude of N2 was less pronounced in erroneous saccades (ES) than correct saccades (CS), whereas ERN and P3 mean amplitudes were more pronounced in ES. Moreover, the P3 mean amplitude of ES predicted the percentage of ES at both follow up-measurements irrespective of the applied stimulation (sham vs. verum). N2 in trials with correct saccades were negatively correlated with nonplanning trait impulsivity, while P3 in erroneous antisaccade trials was negatively correlated with food-related impulsivity. Overall, the findings of reduced ERN, enhanced P3 and N2 amplitude might be interpreted as difficulties in response inhibition towards food in individuals with BED. In particular, P3 predicts task outcome at follow-up and might represent a potential marker for inhibitory control processes.