Transcranial direct current stimulation in psychiatric disorders

The interest in non-invasive brain stimulation techniques is increasing in recent years. Among these techniques, transcranial direct current stimulation (tDCS) has been the subject of great interest among researchers because of its easiness to use, low cost, benign profile of side effects and encouraging results of research in the field. This interest has generated several studies and randomized clinical trials, particularly in psychiatry. In this review, we provide a summary of the development of the technique and its mechanism of action as well as a review of the methodological aspects of randomized clinical trials in psychiatry, including studies in affective disorders, schizophrenia, obsessive compulsive disorder, child psychiatry and substance use disorder. Finally, we provide an overview of tDCS use in cognitive enhancement as well as a discussion regarding its clinical use and regulatory and ethical issues. Although many promising results regarding tDCS efficacy were described, the total number of studies is still low, highlighting the need of further studies aiming to replicate these findings in larger samples as to provide a definite picture regarding tDCS efficacy in psychiatry.     

Transcranial direct current stimulation for knee osteoarthritis: a single-blind randomized sham-controlled trial

ObjectiveTo evaluate the effects of transcranial direct current stimulation on pain and other symptoms of knee osteoarthritis.MethodsWe performed a single-blind randomized sham-controlled trial with two parallel arms in an outpatient clinic of physical medicine and rehabilitation at a teaching hospital. We randomized 54 patients, 30–70 years of age, with knee osteoarthritis into two groups. They had morning stiffness ≤ 30 min, knee pain ≥ 3 months, joint crepitus, and Kellgren-Lawrence grade 1 or 2 on radiographs. For the active stimulation we administered 2 mA current, 20 min for each session and for the sham group 30 s stimulation and 20 min no current. Using the 10/20 International EEG system, the anode was fixed over the contralateral primary motor cortex (C3 or C4), and the cathode was placed on the ipsilateral supraorbital region (Fp1 or Fp2), with respect to the included knee. The program was repeated once daily over 5 consecutive days. Both groups received acetaminophen. We assessed the patients before and after the interventions, and three months post-intervention. The primary outcome was knee pain on the visual analog scale, and the secondary outcome was the Knee injury and Osteoarthritis Outcome Score.ResultsThere was a statistically significant reduction in the intensity of pain within sham and active groups (both p < 0.001), but no significant difference between the groups (p = 0.226). Analyses of the Knee injury and Osteoarthritis Outcome Scores showed no clinically important changes.ConclusionsTranscranial direct current stimulation does not reduce knee pain, does not abate other symptoms, and does not restore knee function in patients with knee osteoarthritis. The pain reduction in our study could be attributed to either placebo or the acetaminophen effect.     

Transcranial direct current stimulation in Parkinson's disease: Neurophysiological mechanisms and behavioral effects

Recent research has highlighted the potential of transcranial direct current stimulation (tDCS) to complement rehabilitation effects in the elderly and in patients with neurological diseases, including Parkinson's disease (PD). TDCS can modulate cortical excitability and enhance neurophysiological mechanisms that compensate for impaired learning in PD. The objective of this systematic review is to provide an overview of the effects of tDCS on neurophysiological and behavioral outcome measures in PD patients, both as a stand-alone and as an adjunctive therapy. We systematically reviewed the literature published throughout the last 10 years. Ten studies were included, most of which were sham controlled. Results confirmed that tDCS applied to the motor cortex had significant results on motor function and to a lesser extent on cognitive tests. However, the physiological mechanism underlying the long-term effects of tDCS on cortical excitability in the PD brain are still unclear and need to be clarified in order to apply this technique optimally to a wider population in the different disease stages and with different medication profiles.     

Transcranial direct current stimulation in disorders of consciousness: a review

It is a challenge to evaluate and treat the patients with disorders of consciousness (DOC) in the clinic. Due to the huge costs of prolonged intensive care, the management of these patients raises great financial strain on families and important ethical questions. To date, several studies have attempted to specifically detect pharmacologic or non-pharmacologic effectiveness, and until now, there are no evidence-based guidelines about the treatment of patients with DOC. Recently, because of ethical and procedural limitations on the use of invasive stimulation techniques, non-invasive brain stimulation, such as the transcranial direct current stimulation (tDCS), has been investigated for improving the level of consciousness in patients with DOC. This paper briefly reviewed the key clinical investigations using tDCS with the aim of better understanding the pathophysiological mechanism of DOC or improving the level of consciousness in patients with DOC. In conclusion, some beneficial results of tDCS protocols have been shown in patients with DOC, especially targeting the left dorsolateral prefrontal cortex in minimally conscious state. However, these investigations must be continued in larger controlled, randomized, blinded and prospective studies in order to transpose these preliminary data to clinical effects. Furthermore, an encouraging perspective for the future is the combination of neurophysiological or functional neuroimaging techniques with non-invasive brain stimulation to evaluate neuro-modulatory effects of stimulation in patients with DOC.     

Transcranial direct current stimulation of the motor cortex induces distinct changes in thermal and mechanical sensory percepts

Objective

The aim of this single-blinded, complete crossover study was to evaluate the effects of tDCS on thermal and mechanical perception, as assessed by quantitative sensory testing (QST).

Methods

QST was performed upon the radial part of both hands of eight healthy subjects (3 female, 5 male, 25–41 years of age). These subjects were examined before and after cathodal, anodal or sham tDCS, applied in a random order. TDCS was administered for 15 min at a 1 mA current intensity, with the active electrode placed over the left primary motor cortex and the reference electrode above the right orbit.

Results

After cathodal tDCS, cold detection thresholds (CDT), mechanical detection thresholds (MDT), and mechanical pain thresholds (MPT) significantly increased in the contralateral hand, when compared to the baseline condition.

Conclusions

Cathodal tDCS temporarily reduced the sensitivity to A-fiber mediated somatosensory inputs.

Significance

Impairment of these somatosensory percepts suggests a short-term suppression of lemniscal or suprathalamic sensory pathways following motor cortex stimulation by cathodal tDCS.     

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).     

Transcranial direct current stimulation for the treatment of focal hand dystonia

The treatment of writer's cramp, a task‐specific focal hand dystonia, needs new approaches. A deficiency of inhibition in the motor cortex might cause writer's cramp. Transcranial direct current stimulation modulates cortical excitability and may provide a therapeutic alternative. In this randomized, double‐blind, sham‐controlled study, we investigated the efficacy of cathodal stimulation of the contralateral motor cortex in 3 sessions in 1 week. Assessment over a 2‐week period included clinical scales, subjective ratings, kinematic handwriting analysis, and neurophysiological evaluation. Twelve patients with unilateral dystonic writer's cramp were investigated; 6 received transcranial direct current and 6 sham stimulation. Cathodal transcranial direct current stimulation had no favorable effects on clinical scales and failed to restore normal handwriting kinematics and cortical inhibition. Subjective worsening remained unexplained, leading to premature study termination. Repeated sessions of cathodal transcranial direct current stimulation of the motor cortex yielded no favorable results supporting a therapeutic potential in writer's cramp. © 2011 Movement Disorder Society     

Transcranial direct current stimulation disrupts tactile perception

The excitability of the cerebral cortex can be modulated by various transcranial stimulation techniques. Transcranial direct current stimulation (tDCS) offers the advantage of portable equipment and could, therefore, be used for ambulatory modulation of brain excitability. However, modulation of cortical excitability by tDCS has so far mostly been shown by indirect measures. Therefore, we examined whether tDCS has a direct behavioral/perceptional effect. We compared tactile discrimination of vibratory stimuli to the left ring finger prior to, during and after tDCS applied for 7 min at 1-mA current intensity in 13 subjects. Stimulation was pseudorandomized into cathodal, anodal and sham conditions in a within-subject design. The active electrode was placed over the corresponding somatosensory cortex at C4 according to the 10-20 EEG system and the reference electrode at the forehead above the contralateral orbita. Cathodal stimulation compared with sham induced a prolonged decrease of tactile discrimination, while anodal and sham stimulation did not. Thus, cortical processing can be modulated in a behaviorally/perceptually meaningful way by weak transcranial current stimulation applied through portable technology. This finding offers a new perspective for the treatment of conditions characterized by alterations of cortical excitability.     

Transcranial direct current stimulation enhances mu rhythm desynchronization during motor imagery that depends on handedness

Transcranial direct current stimulation (tDCS) can modulate the amplitude of event-related desynchronization (ERD) that appears on the electroencephalogram (EEG) during motor imagery. To study the effect of handedness on the modulating effect of tDCS, we compared the difference in tDCS-boosted ERD during dominant and non-dominant hand motor imagery. EEGs were recorded over the left sensorimotor cortex of seven healthy right-handed volunteers, and we measured ERD induced either by dominant or non-dominant hand motor imagery. Ten minutes of anodal tDCS was then used to increase the cortical excitability of the contralateral primary motor cortex (M1), and ERD was measured again. With anodal tDCS, we observed only a small increase in ERD during non-dominant hand motor imagery, whereas the same stimulation induced a prominent increase in ERD during dominant hand motor imagery. This trend was most obvious in the participants who used their dominant hand more frequently. Although our study is preliminary because of a small sample size, these results suggest that the increase in ERD by applying anodal tDCS was stronger on the dominant side than on the non-dominant side. The background excitability of M1 may determine the strength of the effect of anodal tDCS on ERD by hand motor imagery.     

Transcranial direct current stimulation improves tinnitus perception and modulates cortical electrical activity in patients with tinnitus: A randomized clinical trial

ObjectivesThis study aims to determine whether transcranial direct current stimulation (tDCS): a) is effective in the treatment of tinnitus by decreasing its annoyance and severity; b) modulates the cortical electrical activity of such individuals.MethodsA double-blind, placebo-controlled clinical trial was conducted with 24 patients with tinnitus, randomized into two groups: Group 1 (n = 12) received anodal tDCS over the left temporoparietal area (LTA) and cathodal tDCS over the right dorsolateral prefrontal cortex (DLPFC) and Group 2 (n = 12) received placebo intervention. Tinnitus perception using a visual analog scale (VAS) and the Tinnitus Handicap Inventory (THI) questionnaire, in addition to electroencephalogram (EEG) was measured with eyes opened and closed at baseline and after the intervention. For the treatment, patients were subjected to five consecutive sessions of tDCS with the anodal electrode over the LTA and cathodal electrode over the right DLPFC (7 × 5 cm, 2 mA for 20 min). tDCS was turned off after 30 s in the sham group.ResultsActive tDCS significantly improved tinnitus annoyance and severity. It was associated with decreased beta and theta EEG frequency bands with eyes opened and decreased alpha frequency with eyes closed. sLORETA identified changes in frequency bands in the frontal, temporoparietal, and limbic regions. Finally, there were negative correlations between baseline EEG frequency bands and tDCS-induced change in tinnitus annoyance and severity.ConclusionsThese results demonstrate that tDCS modulates the EEG activity and alleviates tinnitus perception. This effect may be related to baseline EEG activity.     

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.     

Transcranial direct current stimulation in inflammatory bowel disease patients modifies resting-state functional connectivity: A RCT

BackgroundChronic pain is known to be associated with functional and structural changes in the brain. Inflammatory bowel disease (IBD) presents with chronic abdominal pain in almost 35% of all patients.This study investigates structural and functional changes in magnetic resonance imaging (MRI) after transcranial direct current stimulation (tDCS) applied to ameliorate pain in IBD.MethodsThis phase-III, placebo-controlled, randomized study included 36 patients with IBD and chronic pain. MRI scans were performed before and following tDCS, which was applied for 5 days.Results/conclusionFor the first time, this study revealed an association of changes in resting-state functional MRI and pain reduction in IBD. There was a significant increase in functional connectivity after active tDCS within the visual medial and the right frontoparietal network being connected with the amygdala, the insula, and the primary somatosensory cortex indicating central pain mechanisms in IBD. Moreover, tDCS offers a novel therapeutic strategy for abdominal pain.     

Transcranial direct current stimulation improves seizure control in patients with Rasmussen encephalitis

Aim. Rasmussen encephalitis is associated with severe seizures that are unresponsive to antiepileptic drugs, as well as immunosuppressants. Transcranial direct current stimulation (t‐DCS) is a non‐invasive and safe method tried mostly for focal epilepsies with different aetiologies. To date, there is only one published study with two case reports describing the effect of t‐DCS in Rasmussen encephalitis. Our aim was to investigate the effect of t‐DCS on seizures in Rasmussen encephalitis and to clarify its safety. Methods. Five patients (mean age: 19; three females), diagnosed with Rasmussen encephalitis were included in this study. Patients received first cathodal, then anodal (2 mA for 30 minutes on three consecutive days for non‐sham stimulations), and finally sham stimulation with two‐month intervals, respectively. Three patients received classic (DC) cathodal t‐DCS whereas two patients received cathodal stimulation with amplitude modulation at 12 Hz. Afterwards, all patients received anodal stimulation with amplitude modulation at 12 Hz. In the last part of the trial, sham stimulation (a 60‐second stimulation with gradually decreasing amplitude to zero in the last 15 seconds) was applied to three patients. Maximum current density was 571 mA/m2 using 70 mm × 50 mm wet sponge electrodes with 2‐mA maximum, current controlled stimulator, and maximum charge density was 1028 C/m2 for a 30‐minute stimulation period. Results. After cathodal stimulation, all but one patient had a greater than 50% decrease in seizure frequency. Two patients who received modulated cathodal t‐DCS had better results. The longest positive effect lasted for one month. A second trial with modulated anodal stimulation and a third with sham stimulation were not effective. No adverse effect was reported with all types of stimulations. Conclusion. Both classic and modulated cathodal t‐DCS may be suitable alternative methods for improving seizure outcome in Rasmussen encephalitis patients.     

Efficacy of pre-supplementary motor area transcranial direct current stimulation for treatment resistant obsessive compulsive disorder: A randomized,double blinded,sham controlled trial

BackgroundA significant proportion of obsessive compulsive disorder (OCD) patients do not respond to specific serotonin reuptake inhibitors (SSRIs). There is a need to evaluate novel treatment options for OCD.ObjectiveIn this double blinded, randomized, sham controlled study, we investigated the efficacy of add-on transcranial direct current stimulation (tDCS) in reducing the symptoms in SSRI-resistant OCD patients by employing anodal pre-supplementary motor area (pre-SMA) stimulation.MethodTwenty-five patients with DSM-IV OCD having persistent symptoms despite adequate and stable treatment with at least one SSRI were randomly allocated to receive 20 min of verum (active) 2-mA tDCS or sham stimulation twice daily on 5 consecutive days [anode over Pre-SMA; cathode over right supra-orbital area]. Response to treatment was defined as at least 35% reduction in the Yale-Brown Obsessive-Compulsive Scale (YBOCS) total score along with a Clinical Global Impression – Improvement (CGI-I) score of 1 (very much improved) or 2 (much improved).ResultsThe response rate was significantly greater in the verum tDCS(4 out of 12) compared to sham-tDCS (0 out of 13) [Fisher's exact test, p = 0.04]. Repeated measures analysis of variance with tDCS type (verum vs. sham) as between subjects factor showed that there was a significant tDCS-type X time-point interaction with significantly greater reduction of YBOCS total score [F (1,22) = 4.95,p = 0.04,partial-η² = 0.18] in verum-tDCS group.ConclusionsThe results of this RCT suggest that tDCS may be effective in treating SSRI-resistant OCD. Future studies should examine the efficacy in larger samples of OCD and explore other potential target regions using randomized sham-controlled designs, in addition to examining the sustainability of the beneficial effects.Trial registrationClinical Trials Registry India (http://ctri.nic.in/Clinicaltrials/login.php): Registration Number- CTRI/2016/04/006837).     

Transcranial direct current stimulation during treadmill training in children with cerebral palsy: A randomized controlled double-blind clinical trial

Impaired gait constitutes an important functional limitation in children with cerebral palsy (CP). Treadmill training has achieved encouraging results regarding improvements in the gait pattern of this population. Moreover, transcranial direct current stimulation (tDCS) is believed to potentiate the results achieved during the motor rehabilitation process. The aim of the present study was to determine the effect of the administration of tDCS during treadmill training on the gait pattern of children with spastic diparetic CP. A double-blind randomized controlled trial was carried out involving 24 children with CP allocated to either an experimental group (active anodal tDCS [1 mA] over the primary motor cortex of the dominant hemisphere) or control group (placebo tDCS) during ten 20-min sessions of treadmill training. The experimental group exhibited improvements in temporal functional mobility, gait variables (spatiotemporal and kinematics variables). The results were maintained one month after the end of the intervention. There was a significant change in corticospinal excitability as compared to control group. In the present study, the administration of tDCS during treadmill training potentiated the effects of motor training in children with spastic diparetic CP.     

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.     

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.