The use of tDCS and CVS as methods of non-invasive brain stimulation

Transcranial direct current stimulation (tDCS) and caloric vestibular stimulation (CVS) are safe methods for selectively modulating cortical excitability and activation, respectively, which have recently received increased interest regarding possible clinical applications. tDCS involves the application of low currents to the scalp via cathodal and anodal electrodes and has been shown to affect a range of motor, somatosensory, visual, affective and cognitive functions. Therapeutic effects have been demonstrated in clinical trials of tDCS for a variety of conditions including tinnitus, post-stroke motor deficits, fibromyalgia, depression, epilepsy and Parkinson's disease. Its effects can be modulated by combination with pharmacological treatment and it may influence the efficacy of other neurostimulatory techniques such as transcranial magnetic stimulation. CVS involves irrigating the auditory canal with cold water which induces a temperature gradient across the semicircular canals of the vestibular apparatus. This has been shown in functional brain-imaging studies to result in activation in several contralateral cortical and subcortical brain regions. CVS has also been shown to have effects on a wide range of visual and cognitive phenomena, as well as on post-stroke conditions, mania and chronic pain states. Both these techniques have been shown to modulate a range of brain functions, and display potential as clinical treatments. Importantly, they are both inexpensive relative to other brain stimulation techniques such as electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS).     

Can transcranial direct current stimulation (tDCS) alleviate symptoms and improve cognition in psychiatric disorders?

Objectives. Since the discovery of psychopharmacological treatments in the early 1950s, followed by the development of second-generation antidepressants and antipsychotics, biological psychiatry has not achieved much progress. Recent technological advances in the field of non-invasive brain stimulation open new perspectives in the treatment of psychiatric disorders. Amongst them, transcranial direct current stimulation (tDCS) modulates cortical excitability and induces long-lasting effects. Here, we aimed at evaluating whether tDCS has potential to be developed as an innovative treatment in psychiatry. Methods. We conducted a systematic review of the current state of development and application of tDCS in psychiatric disorders, exploring clinical and cognitive effects, especially in major depressive disorder (MDD), schizophrenia and substance use disorder. Results. Systematic literature search yielded 40 publications: 22 in MDD, nine in schizophrenia, seven in substance use disorder, one in obsessive–compulsive disorder and one in mania. Our findings indicated beneficial clinical effects of tDCS for MDD and a promising literature in schizophrenia and substance use disorder. Conclusions. Despite methodological differences, the data published to date are promising and supports the use of tDCS as a treatment for psychiatric disorders. However, its place regarding other treatments still has to be determined before becoming a routine clinical treatment.     

A systematic review of the clinical efficacy of transcranial direct current stimulation (tDCS) in psychiatric disorders

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique, which can be used to selectively disrupt patterns of neural activity that are associated with symptoms of mental illness. tDCS has been implemented in numerous therapeutic trials across a range of patient populations, with a rapidly increasing number of studies being published each year. This systematic review aimed to evaluate the efficacy of tDCS in the treatment of psychiatric disorders. Four electronic databases were searched from inception until December 2015 by two independent reviewers, and 66 eligible studies were identified. Depression was the most extensively researched condition, followed by schizophrenia and substance use disorders. Data on obsessive compulsive disorder, generalised anxiety disorder, and anorexia nervosa were also obtained. The quality of included studies was appraised using a standardised assessment framework, which yielded a median score corresponding to “weak” on the three-point scale. This improved to “moderate” when case reports/series were excluded from the analysis. Overall, data suggested that tDCS interventions comprising multiple sessions can ameliorate symptoms of several major psychiatric disorders, both acutely and in the long-term. Nevertheless, the tDCS field is still in its infancy, and several methodological and ethical issues must be addressed before clinical efficacy can truly be determined. Studies probing the mechanisms of action of tDCS and those facilitating the definition of optimised stimulation protocols are warranted. Furthermore, evidence from large-scale, multi-centre randomised controlled trials is required if the transition of this therapy from the laboratory to the clinic is to be considered.     

Stimulation cérébrale non invasive dans le traitement du trouble déficit de l’attention avec ou sans hyperactivité : une revue de la littérature

Objectives

The aim of this review is to summarize the available data in the literature about the therapeutic applications of transcranial magnetic stimulation and transcranial direct current stimulation in attention-deficit hyperactivity disorder (ADHD).

Target specific effects of direct current stimulation in schizo-obsessive disorder: A case report

Transcranial direct current stimulation (tDCS) is a type of non-invasive brain stimulation technique that is explored as an add-on treatment for the alleviation of symptoms across the diverse symptom domains in neuropsychiatric disorders. In psychiatry, data is emerging on the effects of tDCS as an add-on treatment in schizophrenia as well as obsessive-compulsive disorder (OCD). But despite high prevalence, the effectiveness of tDCS in co-morbid schizophrenia and OCD is lacking. This case report for the first time examines the clinical utility with target-specific effects of the add-on tDCS in a patient diagnosed with schizo-obsessive disorder.     

Transcranial direct current stimulation for the treatment of major depressive disorder: a summary of preclinical, clinical and translational findings

Major depressive disorder (MDD) is a common psychiatric illness, with 6-12% lifetime prevalence. It is also among the five most disabling diseases worldwide. Current pharmacological treatments, although relatively effective, present important side effects that lead to treatment discontinuation. Therefore, novel treatment options for MDD are needed. Here, we discuss the recent advancements of one new neuromodulatory technique--transcranial direct current stimulation (tDCS)--that has undergone intensive research over the past decade with promising results. tDCS is based on the application of weak, direct electric current over the scalp, leading to cortical hypo- or hyper-polarization according to the specified parameters. Recent studies have shown that tDCS is able to induce potent changes in cortical excitability as well as to elicit long-lasting changes in brain activity. Moreover, tDCS is a technique with a low rate of reported side effects, relatively easy to apply and less expensive than other neuromodulatory techniques--appealing characteristics for clinical use. In the past years, 4 of 6 phase II clinical trials and one recent meta-analysis have shown positive results in ameliorating depression symptoms. tDCS has some interesting, unique aspects such as noninvasiveness and low rate of adverse effects, being a putative substitutive/augmentative agent for antidepressant drugs, and low-cost and portability, making it suitable for use in clinical practice. Still, further phase II and phase III trials are needed as to better clarify tDCS role in the therapeutic arsenal of MDD.     

Clinical trial design in non-invasive brain stimulation psychiatric research

Major depressive disorder (MDD) trials - investigating either non-pharmacological or pharmacological interventions - have shown mixed results. Many reasons explain this heterogeneity, but one that stands out is the trial design due to specific challenges in the field. We aimed therefore to review the methodology of non-invasive brain stimulation (NIBS) trials and provide a framework to improve clinical trial design. We performed a systematic review for randomized, controlled MDD trials whose intervention was transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) in MEDLINE and other databases from April 2002 to April 2008. We created an unstructured checklist based on CONSORT guidelines to extract items such as power analysis, sham method, blinding assessment, allocation concealment, operational criteria used for MDD, definition of refractory depression and primary study hypotheses. Thirty-one studies were included. We found that the main methodological issues can be divided in to three groups: (1) issues related to phase II/small trials, (2) issues related to MDD trials and, (3) specific issues of NIBS studies. Taken together, they can threaten study validity and lead to inconclusive results. Feasible solutions include: estimating the sample size a priori; measuring the degree of refractoriness of the subjects; specifying the primary hypothesis and statistical tests; controlling predictor variables through stratification randomization methods or using strict eligibility criteria; adjusting the study design to the target population; using adaptive designs and exploring NIBS efficacy employing biological markers. In conclusion, our study summarizes the main methodological issues of NIBS trials and proposes a number of alternatives to manage them.     

Treating Post-traumatic Stress Disorder with Neuromodulation Therapies: Transcranial Magnetic Stimulation,Transcranial Direct Current Stimulation,and Deep Brain Stimulation

Post-traumatic stress disorder (PTSD) is a prevalent and debilitating illness. While standard treatment with pharmacotherapy and psychotherapy may be effective, approximately 20 to 30% of patients remain symptomatic. These individuals experience depression, anxiety, and elevated rates of suicide. For treatment-resistant patients, there is a growing interest in the use of neuromodulation therapies, including transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), and deep brain stimulation (DBS). We conducted a systematic review on the use of neuromodulation strategies for PTSD and pooled 13 randomized clinical trials (RCTs), 11 case series, and 6 case reports for analysis. Overall, most studies reported favorable outcomes in alleviating both PTSD and depressive symptoms. Although several RCTs described significant differences when active and sham stimulations were compared, others found marginal or nonsignificant differences between groups. Also positive were studies comparing PTSD symptoms before and after treatment. The side effect profile with all 3 modalities was found to be low, with mostly mild adverse events being reported. Despite these encouraging data, several aspects remain unknown. Given that PTSD is a highly heterogeneous condition that can be accompanied by distinct psychiatric diagnoses, defining a unique treatment for this patient population can be quite challenging. There has also been considerable variation across trials regarding stimulation parameters, symptomatic response, and the role of adjunctive psychotherapy. Future studies are needed to address these issues.Electronic supplementary materialThe online version of this article (10.1007/s13311-020-00871-0) contains supplementary material, which is available to authorized users.Key Words: Post-traumatic stress disorder (PTSD), neuromodulation, transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), deep brain stimulation (DBS)     

Therapeutic potential of brain stimulation techniques in the treatment of mental,psychiatric, and cognitive disorders

Treatment for brain diseases has been disappointing because available medications have failed to produce clinical response across all the patients. Many patients either do not respond or show partial and inconsistent effect, and even in patients who respond to the medications have high relapse rates. Brain stimulation has been seen as an alternative and effective remedy. As a result, brain stimulation has become one of the most valuable therapeutic tools for combating against brain diseases. In last decade, studies with the application of brain stimulation techniques not only have grown exponentially but also have expanded to wide range of brain disorders. Brain stimulation involves passing electric currents into the cortical and subcortical area brain cells with the use of noninvasive as well as invasive methods to amend brain functions. Over time, technological advancements have evolved into the development of precise devices; however, at present, most used noninvasive techniques are repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), whereas the most common invasive technique is deep brain stimulation (DBS). In the current review, we will provide an overview of the potential of noninvasive (rTMS and tDCS) and invasive (DBS) brain stimulation techniques focusing on the treatment of mental, psychiatric, and cognitive disorders.     

Prefrontal tDCS and sertraline in obsessive compulsive disorder: a case report and review of the literature

Obsessive-compulsive (OC) disorder is a disabling disorder resulting in tremendous individual and social burden. It has a large overlap with depression and anxiety disorders and shows treatment resistance in a relevant proportion of patients. Since a couple of years, different noninvasive brain stimulation methods have been investigated to improve OC symptoms. The application of transcranial direct current stimulation (tDCS) has shown inconsistent results which can probably be attributed to a lack in randomized controlled trials with adequate sample size. Anodal stimulation of pre-supplementary motor areas has shown promising results, and there is also sparse data on orbitofrontal and prefrontal stimulation. Here, we provide the first report on a patient with treatment-refractory OC disorder treated with sertraline and an enhanced prefrontal tDCS protocol (twice per day, 10 days) with a classic left-anodal/right cathodal montage, experiencing a 22% reduction of OC symptoms as well as reduction in depression (?10%) and anxiety symptoms (?21%). Due to multifactorial origin of OC disorder and the variety of brain circuits involved, there are probably multiple approaches for brain stimulation regarding site, polarity, and frequency to be assessed in future studies.     

Concurrent conventional & high-definition transcranial direct current stimulation for treatment of schizophrenia with co-morbid obsessive-compulsive disorder: A case report

Non-invasive brain stimulation techniques such as conventional transcranial direct current stimulation (tDCS) and high definition tDCS (HD-tDCS) are increasingly being used as add-on treatment options in schizophrenia and obsessive-compulsive disorder (OCD). This is reporting of the use of a novel accelerated, symptom-specific, add-on tDCS (combining conventional and high definition) protocol in a patient with both schizophrenia and OCD. The intervention showed clinical utility by reducing both schizophrenia and OCD symptoms.     

Exploring Patient Perceptions of Noninvasive Brain Stimulation: A Systematic Review

ObjectiveTo synthesize and critically appraise literature exploring patient perceptions regarding the therapeutic use of noninvasive brain stimulation.Material and MethodsA systematic search of CINHAL, PUBMED, Web of Science, and Medline was performed. Reference lists of relevant articles were also screened. Studies exploring participant perceptions regarding the therapeutic use of noninvasive brain stimulation were eligible for inclusion. Perceptions were divided into three domains: knowledge, experience, and attitudes. Noninvasive brain stimulation was defined as any neuromodulation technique that alters brain activity but does not require invasive methods such as surgery. No restrictions were placed upon study design or participant population. Two reviewers performed data extraction and risk of bias assessment. Data relating to methodological characteristics, participant demographics, type of noninvasive brain stimulation, and nature of perceptions (knowledge, experience, or attitudes) were extracted.ResultsFour studies comprising data from 163 participants met the inclusion criteria. All studies investigated perceptions of repetitive transcranial magnetic stimulation (rTMS) in psychiatric populations. Most participants perceived rTMS to be safe and beneficial, demonstrated low levels of fear, and were willing to recommend the intervention to others. No studies were found investigating patient perception of transcranial direct current stimulation (tDCS).ConclusionThe findings from this review suggest that rTMS is well accepted as a therapeutic treatment among psychiatric populations, providing support for its clinical utility. Future work is needed to determine if similar findings exist for other conditions (eg, chronic pain) and for other therapeutic forms of brain stimulation (eg, tDCS).     

Implications from translational cross-validation of clinical assessment tools for diagnosis and treatment in psychiatry

Traditional therapeutic methods in psychiatry, such as psychopharmacology and psychotherapy help many people suffering from mental disorders, but in the long-term prove to be effective in a relatively small proportion of those affected. Therapeutically, resistant forms of mental disorders such as schizophrenia, major depressive disorder, and bipolar disorder lead to persistent distress and dysfunction in personal, social, and professional aspects. In an effort to address these problems, the translational approach in neuroscience has initiated the inclusion of novel or modified unconventional diagnostic and therapeutic techniques with promising results. For instance, neuroimaging data sets from multiple modalities provide insight into the nature of pathophysiological mechanisms such as disruptions of connectivity, integration, and segregation of neural networks, focusing on the treatment of mental disorders through instrumental biomedical methods such as electro-convulsive therapy (ECT), transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS) and deep brain stimulation (DBS). These methodologies have yielded promising results that have yet to be understood and improved to enhance the prognosis of the severe and persistent psychotic and affective disorders. The current review is focused on the translational approach in the management of schizophrenia and mood disorders, as well as the adaptation of new transdisciplinary diagnostic tools such as neuroimaging with concurrently administered psychopathological questionnaires and integration of the results into the therapeutic framework using various advanced instrumental biomedical tools such as ECT, TMS, tDCS and DBS.     

Transcranial direct current stimulation (tDCS) for depression in pregnancy: A pilot randomized controlled trial

BackgroundDepression in pregnancy negatively affects maternal-child health. Transcranial direct current stimulation (tDCS), a non-invasive brain stimulation treatment for depression, has not been evaluated in pregnancy.ObjectiveTo conduct a pilot randomized controlled trial (RCT) to evaluate tDCS for antenatal depression.MethodsIn this pilot RCT in Toronto, Ontario (October 2014 to December 2016), adult pregnant women 14–32 weeks gestation with major depressive disorder who had declined antidepressant medication were considered for inclusion. Participants were randomly assigned 1:1 to tDCS or sham-control. Active tDCS comprised 30-min sessions of 2 mAmp direct current delivered over the dorsolateral prefrontal cortex, 5 days per week, for 3 weeks. Sham was administered similarly, but with current turned off after 30 s. Main outcomes were feasibility, acceptability, and protocol adherence. Maternal Montgomery Asperg Depression Rating Scale (MADRS) was measured post-treatment and at 4 and 12 weeks postpartum.ResultsOf 20 women randomized, 16 completed treatment and provided data (124 tDCS, 122 sham sessions). Views of treatment were positive with no serious adverse events. Post-treatment estimated marginal mean MADRS scores were 11.8 (standard error, SE 2.66) for tDCS and 15.4 (SE 2.51) for sham (p = 0.34). At 4 weeks postpartum, 75.0% of tDCS women were remitted versus 12.5% sham-control (p = 0.04).ConclusionsResults support proceeding to a definitive RCT to evaluate tDCS for antenatal depression. The preliminary efficacy estimates immediately post-treatment and in the postpartum, are encouraging with respect to the potential use of tDCS to improve treatment rates in this population. The trial was registered at: clinical trials.gov (NCT02116127).     

Brain Stimulation: New Vistas for the Exploration and Treatment of Tinnitus

Aims : Tinnitus, the perception of sounds or noise in the absence of auditory stimuli, is a frequent and often severely disabling symptom of different disorders of the auditory system. Attempts to develop evidence‐based therapies have been thwarted by a poor understanding of the underlying pathophysiology. However, recent work points toward a pivotal role of maladaptive cortical reorganization in the generation and perpetuation of tinnitus. Changes in the representation of sounds, abnormalities of oscillatory activity, and hyperactivity in higher order areas of auditory processing have been linked with the perception of tinnitus. Brain stimulation techniques have entered the field and have opened exciting new perspectives for the modulation of dysfunctional brain activity. In this review, a comprehensive overview on the use of brain‐stimulation techniques in the exploration and experimental treatment of tinnitus is provided. Discussions : Noninvasive and invasive brain stimulation techniques, for example, transcranial magnetic stimulation (TMS), direct current stimulation (tDCS), and direct electrical cortical stimulation gave rise to a new line of investigation in tinnitus research. First, it has been shown that focal interference with presumably pathological cortical function can reduce tinnitus at least transiently. Second, the reduction of tinnitus‐associated enhancement of cortical activity by neuronavigated TMS has been demonstrated to ameliorate tinnitus. Third, preliminary data suggest that repeated application of TMS or continuous cortical stimulation may lead to a longer lasting suppression of tinnitus. Conclusions : These proof of principle studies point toward a new option for the investigation and neurophysiology based treatment of tinnitus. Based on these findings, larger scale randomized clinical trials are needed to explore the efficacy of different brain stimulation techniques and parameters as well as the optimal target sites and treatment schedules. Particularly, a careful evaluation of clinical relevance under consideration of an adequate sham control and attention to possible unwanted side effects of these new interventions are indispensable.     

The effects of medication use in transcranial direct current stimulation: A brief review

Background

There has been increased interest in the potential use of transcranial direct current stimulation (tDCS) as treatment for multiple conditions including depression, pain, and cognitive impairment. However, few studies account for the possible influence of comorbid medications when conducting tDCS research.

Supervised transcranial direct current stimulation (tDCS) at home: A guide for clinical research and practice

BackgroundTranscranial direct current stimulation (tDCS) is a method of noninvasive neuromodulation and potential therapeutic tool to improve functioning and relieve symptoms across a range of central and peripheral nervous system conditions. Evidence suggests that the effects of tDCS are cumulative with consecutive daily applications needed to achieve clinically meaningful effects. Therefore, there is growing interest in delivering tDCS away from the clinic or research facility, usually at home.ObjectiveTo provide a comprehensive guide to operationalize safe and responsible use of tDCS in home settings for both investigative and clinical use.MethodsProviding treatment at home can improve access and compliance by decreasing the burden of time and travel for patients and their caregivers, as well as to reach those in remote locations and/or living with more advanced disabilities.ResultsTo date, methodological approaches for at-home tDCS delivery have varied. After implementing the first basic guidelines for at-home tDCS in clinical trials, this work describes a comprehensive guide for facilitating safe and responsible use of tDCS in home settings enabling access for repeated administration over time.ConclusionThese guidelines provide a reference and standard for practice when employing the use of tDCS outside of the clinic setting.     

Transcranial direct current stimulation for auditory verbal hallucinations:a systematic review of clinical trials

Transcranial direct current stimulation(tDCS) has been reportedly beneficial for different neurodegenerative disorders. tDCS has been reported as a potential adjunctive or alternative treatment for auditory verbal hallucination(AVH). This study aims to review the effects of tDCS on AVH in patients with schizophrenia through combining the evidence from randomized clinical trials(RCTs). The databases of PsycINFO(2000–2019), PubMed(2000–2019), EMBASE(2000–2019), CINAHL(2000–2019), Web of Science(2000–2019), and Scopus(2000–2019) were systematically searched. The clinical trials with RCT design were selected for final analysis. A total of nine RCTs were eligible and included in the review. Nine RCTs were included in the final analysis. Among them, six RCTs reported a significant reduction of AVH after repeated sessions of tDCS, whereas three RCTs did not show any advantage of active tDCS over sham tDCS. The current studies showed an overall decrease of approximately 28% of AVH after active tDCS and 10% after sham tDCS. The tDCS protocols targeting the sensorimotor frontal-parietal network showed greater treatment effects compared with the protocols targeting other regions. In this regard, cathodal tDCS over the left temporoparietal area showed inhibitory effects on AVHs. The most effective tDCS protocol on AVHs was twice-daily sessions(2 mA, 20-minute duration) over 5 consecutive days(10 sessions) with the anode over the left dorsolateral prefrontal cortex and the cathode over the left temporal area. Some patient-specific and diseasespecific factors such as young age, nonsmoking status, and higher frequencies of AVHs seemed to be the predictors of treatment response. Taken together, the results of tDCS as an alternative treatment option for AVH show controversy among current literatures, since not all studies were positive. However, the studies targeting the same site of the brain showed that the tDCS could be a promising treatment option to reduce AVH. Further RCTs, with larger sample sizes, should be conducted to reach a conclusion on the efficacy of tDCS for AVH and to develop an effective therapeutic protocol for clinical setting.     

The effects of transcranial direct current stimulation on upper-limb function post-stroke: A meta-analysis of multiple-session studies

ObjectiveTo systematically review how patient characteristics and/or transcranial direct current stimulation (tDCS) parameters influence tDCS effectiveness in respect to upper limb function post-stroke.MethodsThree electronic databases were searched for sham-controlled randomised trials using the Fugl-Meyer Assessment for upper extremity as outcome measure. A meta-analysis and nine subgroup-analyses were performed to identify which tDCS parameters yielded the greatest impact on upper limb function recovery in stroke patients.ResultsEighteen high-quality studies (507 patients) were included. tDCS applied in a chronic stage yields greater results than tDCS applied in a (sub)acute stage. Additionally, patients with low baseline upper limb impairments seem to benefit more from tDCS than those with high baseline impairments. Regarding tDCS configuration, all stimulation types led to a significant improvement, but only tDCS applied during therapy, and not before therapy, yielded significant results. A positive dose–response relationship was identified for current/charge density and stimulation duration, but not for number of sessions.ConclusionOur results demonstrate that tDCS improves upper limb function post-stroke. However, its effectiveness depends on numerous factors. Especially chronic stroke patients improved, which is promising as they are typically least amenable to recovery.SignificanceThe current work highlights the importance of several patient-related and protocol-related factors regarding tDCS effectiveness.     

Non-invasive Brain Stimulation Therapy in Multiple Sclerosis: A Review of tDCS,rTMS and ECT Results

BackgroundMultiple sclerosis (MS) is a disabling neurological disorder presenting a variety of symptoms which are hard to control by actual drug regimens. Non-invasive brain stimulation (NIBS) techniques have been investigated in the past years for the improvement of several neurologic and psychiatric disorders.ObjectiveHere, we review the application of transcranial direct current stimulation (tDCS), transcranial magnetic stimulation (rTMS, iTBS) and electroconvulsive therapy (ECT) in MS patients.MethodsArticles were searched in common literature databases. Crosslinks were reviewed.ResultsECT was shown to be efficacious for the treatment of severe psychiatric disorders in 21 case reports. The results of tDCS and TMS for the treatment of depressive symptoms, fatigue, tactile sensory deficit, pain, motor performance, and spasticity were assessed in several studies and showed mixed results.ConclusionsOverall, data for the treatment of MS with NIBS is sparse regarding TMS and tDCS. Treatment of severe psychiatric disorders with ECT is only reported in single cases. More studies are needed to elucidate the potential role of NIBS in MS treatment.