Treatment of depression with transcranial direct current stimulation (tDCS): A Review

Major Depression Disorder (MDD) is usually accompanied by alterations of cortical activity and excitability, especially in prefrontal areas. These are reflections of a dysfunction in a distributed cortico-subcortical, bihemispheric network. Therefore it is reasonable to hypothesize that altering this pathological state with techniques of brain stimulation may offer a therapeutic target. Besides repetitive transcranial magnetic stimulation, tonic stimulation with weak direct currents (tDCS) modulates cortical excitability for hours after the end of stimulation, thus, it is a promising non-invasive therapeutic option. Early studies from the 1960s suggested some efficacy of DC stimulation to reduce symptoms in depression, but mixed results and development of psychotropic drugs resulted in an early abandonment of this technique. In the last years tDCS protocols have been optimized. Application of the newly developed stimulation protocols in patients with major depression has shown promise in few pilot studies. Further studies are needed to identify the optimal parameters of stimulation and the clinical and patient characteristics that may condition response to tDCS.     

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.     

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.     

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.     

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

BackgroundInhibitory 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.ObjectiveThe 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.MethodsA 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.ResultsResults 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.ConclusionBased 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.     

The effects of repeated transcranial direct current stimulation on sleep quality and depression symptoms in patients with major depression and insomnia

ImportanceAlthough several strategies using transcranial direct current stimulation (tDCS) have been investigated to treat major depressive disorder (MDD), the efficacy of this treatment for patients with MDD who also have insomnia is unclear.ObjectiveTo observe the effects of tDCS on sleep quality and depressive symptoms in patients with MDD who have insomnia.MethodsWe conducted a randomized, double-blinded study involving adults with major depression and insomnia. We randomly assigned patients to either add tDCS or to sham tDCS to their regular treatment. After randomization, we treated a total of 90 patients at the Kangning Hospital, Ningbo, China. We allocated 47 patients to the tDCS group and 43 to the sham tDCS group. The tDCS treatment procedure included 20 sessions of 2-mA stimulation of the dorsolateral prefrontal cortex (DLPFC) for 30 min, which was followed by four weekly treatments. The anode and cathode electrodes were placed on the left and right DLPFC, respectively. We recorded the Self-rating Depression Scale (SDS), Self-rating Anxiety Scale (SAS), Pittsburgh Sleep Quality Inventory (PSQI), and Polysomnography (PSG) at Day 1 and Day 28.ResultsCompared with the sham tDCS group, the active tDCS group showed improved total scores of SAS and SDS. PSQI total score and all PSQI sub-divisions, except for “sleep duration and sleep efficiency,” significantly improved after treatment. We also observed that tDCS affected sleep architecture, by increasing total sleep time and improving sleep efficiency through PSG.ConclusionsOur study demonstrated the effect of tDCS on sleep quality and depressive symptoms in patients with MDD and insomnia. These results suggested that tDCS stimulation not only improved symptoms of depression and anxiety but also had a positive effect on sleep quality in patients with MDD. For patients with depression and insomnia, tDCS stimulation could be a good supplement to drugs.     

Domain-specific suppression of auditory mismatch negativity with transcranial direct current stimulation

ObjectiveTo evaluate the influence of frontal transcranial direct current stimulation (tDCS) on auditory mismatch negativity (MMN).MethodsMMN is an event related potential calculated by subtracting the amplitude of the evoked potentials in response to a “standard” stimulus from the evoked potentials produced by a rare “oddball” stimulus. Here we assessed the influence of anodal tDCS, cathodal tDCS or sham stimulation delivered over the right inferior frontal cortex on MMN in response to duration and frequency auditory deviants in 10 healthy subjects.ResultsMMN to frequency deviants was significantly reduced after anodal tDCS compared with sham or cathodal stimulation which did not change MMN to frequency deviants. Neither anodal nor cathodal tDCS had any effect on MMN to duration deviants.ConclusionsNon-invasive brain stimulation with tDCS can influence MMN. The differing networks known to be activated by duration and frequency deviants could account for the differential effect of tDCS on duration and frequency MMN.SignificanceNon-invasive brain stimulation could be a useful method to manipulate MMN for experimental purposes.     

Cathodal transcranial direct current stimulation affects seizures and cognition in fully amygdala-kindled rats

Abstract

This study evaluated the effects of weak transcranial direct current stimulation (tDCS), a new non-invasive brain stimulation technique, on amygdala-kindled rats. The seizure severity, i.e. seizure stage, afterdischarge duration (ADD), and AD threshold (ADT) in the animals were measured one day after the last cathodal tDCS session, comparing with those of pre-treatment controls. Furthermore, the effects of cathodal tDCS on cognitive function were also studied by a water maze test (WMT) two days after the last tDCS session. Cathodal tDCS treatment significantly improved the seizure stage and decreased ADD together with elevated ADT one day after the last tDCS session. The treatment also showed significant improvement in the performance of WMT. The findings suggest that cathodal tDCS has anticonvulsive after-effects last at least for one day on the amygdale-kindled rats and positively affects cognitive performance.     

Repetitive transcranial magnetic stimulation (rTMS) versus transcranial direct current stimulation (tDCS) in the management of patients with fibromyalgia: A randomized controlled trial

ObjectivesThe aim of this study was to compare the effects of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) on pain and quality of life in patients with fibromyalgia.MethodsThirty participants were randomized into two groups of 15 patients, to receive 3 sessions of either high-frequency (10 Hz) rTMS or 2 mA, 20 min anodal transcranial direct current stimulation over the left dorsolateral prefrontal cortex (DLPFC) over 1 week. Pain was assessed using a Visual Analog Scale (VAS) before treatment, immediately after treatment, 6 and 12 weeks later. Quality of life was evaluated using the Revised Fibromyalgia Impact Questionnaire (FIQR) and psychiatric symptoms were measured using the Depression Anxiety Stress Scale-21 Item (DASS-21) before treatment, and 6 and 12 weeks after treatment.ResultsFor the VAS there was a significant time-group interaction, showing that the behavior of two groups differed regarding changes of VAS in favor of the RTMS group (df = 1.73, F = 4.80, p = <0.016). Time-group interaction effect on DASS-21 and FIQR was not significant. 66.6% of patients in rTMS group and 26.6% of patients in tDCS group experienced at least a 30% reduction of VAS from baseline to last follow-up (p = 0.028).DiscussionWith the methodology used in this study, both rTMS and tDCS were safe modalities and three sessions of rTMS over DLPFC had greater and longer lasting analgesic effects compared to tDCS in patients with FM. However, considering the limitations of this study, further studies are needed to explore the most effective modality.     

Tolerability and feasibility of at-home remotely supervised transcranial direct current stimulation (RS-tDCS): Single-center evidence from 6,779 sessions

IntroductionThe ability to deploy transcranial direct current stimulation (tDCS) at home is a key usability advantage to support scaling for pivotal clinical trials. We have established a home-based tDCS protocol for use in clinical trials termed remotely supervised (RS)-tDCS.ObjectiveTo report the tolerability and feasibility of tDCS sessions completed to date using RS-tDCS in clinical trials.MethodsWe analyzed tolerability (i.e., adverse events, AEs) reported in six Class I/II/III trials using RS-tDCS to study symptom outcomes over 10 to 60 daily applications. Across the six clinical trials, 308 participants (18–78 years old) completed an average of 23 sessions for a total of 6779 RS-tDCS administrations. The majority of participants were diagnosed with multiple sclerosis, and open-label trials included those diagnosed with a range of other conditions (e.g., Parkinson's disease, post-stroke aphasia, traumatic brain injury, cerebellar ataxia), with minimum-to-severe neurologic disability. Clinical trial feasibility (i.e., treatment fidelity and blinding integrity) was examined using two Class I randomized controlled trials (RCTs).ResultsNo serious AEs occurred. Across administrations, three sessions (0.04%) were aborted due to discomfort, but no participant discontinued due to tolerability. The AEs most commonly reported by participants were tingling (68%), itching (41%) and warmth sensation (42%) at the electrode site, and these were equally reported in active and sham tDCS conditions. The two Class I RCTs resulted in rapid enrollment, high fidelity to treatment completion, and blinding integrity.ConclusionsAt-home RS-tDCS is tolerable, including when used over extended periods of time. Home-based RS-tDCS is feasible and can enable Class I tDCS clinical trial designs.     

Dual-hemisphere transcranial direct current stimulation improves performance in a tactile spatial discrimination task

ObjectiveThe aim of this study was to test the hypothesis that dual-hemisphere transcranial direct current stimulation (tDCS) over the primary somatosensory cortex (S1) could improve performance in a tactile spatial discriminative task, compared with uni-hemisphere or sham tDCS.MethodsNine healthy adults participated in this double-blind, sham-controlled, and cross-over design study. The performance in a grating orientation task (GOT) in the right index finger was evaluated before, during, immediately after and 30 min after the dual-hemisphere, uni-hemisphere (1 mA, 20 min), or sham tDCS (1 mA, 30 s) over S1. In the dual-hemisphere and sham conditions, anodal tDCS was applied over the left S1, and cathodal tDCS was applied over the right S1. In the uni-hemisphere condition, anodal tDCS was applied over the left S1, and cathodal tDCS was applied over the contralateral supraorbital front.ResultsThe percentage of correct responses on the GOT during dual-hemisphere tDCS was significantly higher than that in the uni-hemisphere or sham tDCS conditions when the grating width was set to 0.75 mm (all p < 0.05).ConclusionsDual-hemisphere tDCS over S1 improved performance in a tactile spatial discrimination task in healthy volunteers.SignificanceDual-hemisphere tDCS may be a useful strategy to improve sensory function in patients with sensory dysfunctions.     

Modulation of creativity by transcranial direct current stimulation

BackgroundCreativity is the use of original ideas to accomplish something innovative. Previous research supports the notion that creativity is facilitated by an activation of the right and/or a deactivation of the left prefrontal cortex. In contrast, recent brain imaging studies suggest that creativity improves with left frontal activation.ObjectiveThe present study was designed to further elucidate the neural basis of and ways to modulate creativity, based on the modulation of prefrontal cortical activity through the non-invasive brain stimulation technique transcranial direct current stimulation (tDCS).MethodsNinety healthy University students performed three tasks on major aspects of creativity: conceptual expansion (Alternate Uses Task, AUT), associative thinking (Compound Remote Associate Task, CRA), and set shifting ability (Wisconsin Card Sorting Task, WCST). Simultaneously, they received cathodal stimulation of the left and anodal stimulation of the right inferior frontal gyrus (IFG), the reverse protocol, or sham stimulation.ResultsThe main pattern of results was a superior performance with bilateral left cathodal/right anodal stimulation, and an inferior performance in the reversed protocol compared to sham stimulation. As a potential underlying physiological mechanism, resting state EEG beta power, indicative of enhanced cortical activity, in the right frontal area increased with anodal stimulation and was associated with better performance.ConclusionThe findings provide new insights into ways of modulating creativity, whereby a deactivation of the left and an activation of the right prefrontal cortex with tDCS is associated with increased creativity. Potential future applications might include tDCS for patients with mental disorders and for healthy individuals in creative professions.     

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.     

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.     

Improving working memory: Exploring the effect of transcranial random noise stimulation and transcranial direct current stimulation on the dorsolateral prefrontal cortex

Objective

The aim of this study was to determine if working memory (WM) performance is significantly improved after the delivery of transcranial random noise stimulation (tRNS) to the left dorsolateral prefrontal cortex (DLPFC), compared to an active comparator or sham.

Methods

Ten participants undertook three experimental sessions in which they received 10 min of anodal tDCS (active comparator), tRNS or sham tDCS whilst performing the Sternberg WM task. Intra-stimulation engagement in a WM task was undertaken as this has been previously shown to enhance the effects of tDCS. Experimental sessions were separated by a minimum of 1 week. Immediately prior to and after each stimulation session the participants were measured on speed and accuracy of performance on an n-back task.

Results

There was significant improvement in speed of performance following anodal tDCS on the 2-back WM task; this was the only significant finding.

Conclusions

The results do not provide support for the hypothesis that tRNS improves WM. However, the study does provide confirmation of previous findings that anodal tDCS enhances some aspects of DLPFC functioning. Methodological limitations that may have contributed to the lack of significant findings following tRNS are discussed.

Significance

Anodal tDCS may have significant implications for WM remediation in psychiatric conditions, particularly schizophrenia.     

Effects of transcranial direct current stimulation on experimental pain perception: A systematic review and meta-analysis

ObjectiveMany studies have examined the effectiveness of transcranial direct current stimulation (tDCS) on human pain perception in both healthy populations and pain patients. Nevertheless, studies have yielded conflicting results, likely due to differences in stimulation parameters, experimental paradigms, and outcome measures. Human experimental pain models that utilize indices of pain in response to well-controlled noxious stimuli can avoid many confounds present in clinical data. This study aimed to assess the robustness of tDCS effects on experimental pain perception among healthy populations.MethodsWe conducted three meta-analyses that analyzed tDCS effects on ratings of perceived pain intensity to suprathreshold noxious stimuli, pain threshold and tolerance.ResultsThe meta-analyses showed a statically significant tDCS effect on attenuating pain-intensity ratings to suprathreshold noxious stimuli. In contrast, tDCS effects on pain threshold and pain tolerance were statistically non-significant. Moderator analysis further suggested that stimulation parameters (active electrode size and current density) and experimental pain modality moderated the effectiveness of tDCS in attenuating pain-intensity ratings.ConclusionThe effectiveness of tDCS on attenuating experimental pain perception depends on both stimulation parameters of tDCS and the modality of experimental pain.SignificanceThis study provides some theoretical basis for the application of tDCS in pain management.     

Effects of direct current stimulation on synaptic plasticity in a single neuron

BackgroundTranscranial direct current stimulation (DCS) has lasting effects that may be explained by a boost in synaptic long-term potentiation (LTP). We hypothesized that this boost is the result of a modulation of somatic spiking in the postsynaptic neuron, as opposed to indirect network effects. To test this directly we record somatic spiking in a postsynaptic neuron during LTP induction with concurrent DCS.MethodsWe performed rodent in-vitro patch-clamp recordings at the soma of individual CA1 pyramidal neurons. LTP was induced with theta-burst stimulation (TBS) applied concurrently with DCS. To test the causal role of somatic polarization, we manipulated polarization via current injections. We also used a computational multi-compartment neuron model that captures the effect of electric fields on membrane polarization and activity-dependent synaptic plasticity.ResultsTBS-induced LTP was enhanced when paired with anodal DCS as well as depolarizing current injections. In both cases, somatic spiking during the TBS was increased, suggesting that evoked somatic activity is the primary factor affecting LTP modulation. However, the boost of LTP with DCS was less than expected given the increase in spiking activity alone. In some cells, we also observed DCS-induced spiking, suggesting DCS also modulates LTP via induced network activity. The computational model reproduces these results and suggests that they are driven by both direct changes in postsynaptic spiking and indirect changes due to network activity.ConclusionDCS enhances synaptic plasticity by increasing postsynaptic somatic spiking, but we also find that an increase in network activity may boost but also limit this enhancement.