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.

[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.

Treatment of major depressive disorder with bilateral theta burst stimulation: study protocol for a randomized, double-blind, placebo-controlled multicenter trial (TBS-D).

Repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex (dlPFC) is currently evolving as an effective and safe therapeutic tool in the treatment of major depressive disorder (MDD). However, already established rTMS treatment paradigms are rather time-consuming. With theta burst stimulation (TBS), a patterned form of rTMS, treatment time can be substantially reduced. Pilot studies and a randomized controlled trial (RCT) demonstrate non-inferiority of TBS to 10 Hz rTMS and support a wider use in MDD. Still, data from placebo-controlled multicenter RCTs are lacking. In this placebo-controlled multicenter study, 236 patients with MDD will be randomized to either intermittent TBS (iTBS) to the left and continuous TBS (cTBS) to the right dlPFC or bilateral sham stimulation (1:1 ratio). The treatment will be performed with 80% resting motor threshold intensity over six consecutive weeks (30 sessions). The primary outcome is the treatment response rate (Montgomery-Asberg Depression Rating Scale reduction ≥ 50%). The aim of the study is to confirm the superiority of active bilateral TBS compared to placebo treatment. In two satellite studies, we intend to identify possible MRI-based and (epi-)genetic predictors of responsiveness to TBS therapy. Positive results will support the clinical use of bilateral TBS as an advantageous, efficient, and well-tolerated treatment and pave the way for further individualization of MDD therapy.Trial registration: ClinicalTrials.gov (NCT04392947).

Effects of 1 mA and 2 mA transcranial direct current stimulation on working memory performance in healthy participants.

Anodal transcranial current stimulation (tDCS) to the left dorsolateral prefrontal cortex (DLPFC) has been shown to enhance working memory (WM) in neuropsychiatric patients. In healthy populations, however, tDCS obtains inconclusive results, mostly due to heterogeneous study and stimulation protocols. Here, we approached these issues by investigating effects of tDCS intensity on simultaneous WM performance with three cognitive loads by directly comparing findings of two double-blind, cross-over, sham-controlled experiments. TDCS was administrated to the left DLPFC at intensity of 1 mA (Experiment 1) or 2 mA (Experiment 2), while participants completed a verbal n-back paradigm (1-, 2-, 3-back). Analysis showed no overall effects of tDCS on WM, but a significant interaction with cognitive load. The present study suggests that cognitive load rather than tDCS intensity could be a decisive factor for effects on WM. Moreover, it emphasizes the need of thorough investigation on study parameters to develop more efficient stimulation protocols.

Meta-analysis of the effects of transcranial direct current stimulation on inhibitory control.

BACKGROUND: Inhibitory control refers to a central cognitive capacity involved in the interruption and correction of actions. Dysfunctions in these cognitive control processes have been identified as major maintaining mechanisms in a range of mental disorders such as ADHD, binge eating disorder, obesity, and addiction. Improving inhibitory control by transcranial direct current stimulation (tDCS) could ameliorate symptoms in a broad range of mental disorders. OBJECTIVE: The primary aim of this pre-registered meta-analysis was to investigate whether inhibitory control can be improved by tDCS in healthy and clinical samples. Additionally, several moderator variables were investigated. METHODS: A comprehensive literature search was performed on PubMed/MEDLINE database, Web of Science, and Scopus. To achieve a homogenous sample, only studies that assessed inhibitory control in the go-/no-go (GNG) or stop-signal task (SST) were included, yielding a total of 75 effect sizes from 45 studies. RESULTS: Results of the meta-analysis indicate a small but significant overall effect of tDCS on inhibitory control (g = 0.21) which was moderated by target and return electrode placement as well as by the task. The small effect size was further reduced after correction for publication bias. CONCLUSION: Based on the studies included, our meta-analytic approach substantiates previously observed differences between brain regions, i.e., involvement of the right inferior frontal gyrus (rIFG) vs. the right dorsolateral prefrontal cortex (rDLPFC) in inhibitory control. Results indicate a small moderating effect of tDCS on inhibitory control in single-session studies and highlight the relevance of technical and behavioral parameters.

Clinical review: The therapeutic use of theta-burst stimulation in mental disorders and tinnitus.

Repetitive Transcranial Magnetic Stimulation (rTMS) is a neuromodulatory treatment intervention, which can be used to alleviate symptoms of mental disorders. Theta-burst stimulation (TBS), an advanced, patterned form of TMS, features several advantages regarding applicability, treatment duration and neuroplastic effects. This clinical review summarizes TBS studies in mental disorders and tinnitus and discusses effectivity and future directions of clinical TBS research. Following the PRISMA guidelines, the authors included 47 studies published until July 2018. Particularly in depression, evidence for the effectiveness of TBS and non-inferiority to conventional rTMS exists. Evidence for therapeutic efficacy of TBS in other mental disorders remains weak due to a large heterogeneity between studies. Rigorous reporting standards and adequately powered controlled trials are indispensable to foster validity and translation into clinical use. Nevertheless, TBS remains a promising instrument to target maladaptive brain networks and to ameliorate psychiatric symptoms.

Improving working memory in schizophrenia: Effects of 1 mA and 2 mA transcranial direct current stimulation to the left DLPFC.

Deficits in various cognitive processes, such as working memory, are characteristic for schizophrenia, lowering patients' functioning and quality of life. Recent research suggests that transcranial direct stimulation (tDCS) applied to the dorsolateral prefrontal cortex (DLPFC) may be a potential therapeutic intervention for cognitive deficits in schizophrenia. Here, we examined the effects of online tDCS to the DLPFC on working memory (WM) performance in 40 schizophrenia patients in two separate experiments with a double blind, sham-controlled, cross-over design. Patients underwent single sessions of active and sham tDCS in a randomized order. Stimulation parameters were anode F3, cathode right deltoid muscle, 21 min tDCS duration, 1 mA tDCS in Experiment 1 (N = 20) and 2 mA tDCS in Experiment 2 (N = 20). Primary outcome was the change in WM performance as measured by a verbal n-back paradigm (1- to 3-back). Irrespective of the stimulation intensity, data analysis showed a significant higher WM accuracy during active tDCS than during sham tDCS (p = 0.019), but no main effect of stimulation intensity (p = 0.392). Subsequent separate analyses revealed a significantly improved WM performance only during 1 mA (p = 0.048). TDCS facilitated WM functioning in schizophrenia, with an advantage of 1 mA over 2 mA. Our results support the notion that tDCS may be a potential treatment for cognitive deficits in schizophrenia and emphasize the need for future research on the specific stimulation parameters.

Treatment of auditory hallucinations with bilateral theta burst stimulation (cTBS): protocol of a randomized, double-blind, placebo-controlled, multicenter trial.

Auditory verbal hallucinations (AH) are core symptoms of schizophrenia. They are often severely distressing and refractory to therapy. Their perception is associated with increased activity in temporoparietal areas of the brain. Repetitive transcranial magnetic stimulation (rTMS) can reduce focal brain hyperactivity and has been shown to ameliorate AH. However, controlled multicenter clinical trials are still missing, effect sizes are moderate, and the treatment with rTMS is time consuming. Continuous theta burst stimulation (cTBS) is a quicker and potentially more effective technique to reduce cortical hyperactivity. First case and pilot studies indicate effectiveness in the treatment of AH. In this randomized, sham-controlled, double-blind multicenter clinical trial, 86 patients with schizophrenia spectrum disorder will be randomized to either cTBS or sham to the left and right temporoparietal cortex during three consecutive weeks (15 sessions totally). In each session, both hemispheres will be stimulated sequentially. The order in the first session (left-right or right-left, respectively) will be determined by randomization and alternated in all following sessions. Primary outcome is the reduction of mean PSYRATS-AH score after cTBS as compared to sham treatment. Follow-up measurements will be performed 1, 3 and 6 months after the end of the treatment. Statistical analysis will be based on the intention-to-treat population including all randomized patients using an analysis of covariance. This multicenter-controlled clinical trial will be able to provide decisive evidence for the efficacy of cTBS in the treatment of AH. The results will be suitable to clarify the role of this innovative, pathophysiology-based therapeutic approach in treatment guidelines for AH. TRIAL REGISTRY: ClinicalTrials.gov identifier: NCT02670291.