Modulatory effects of anodal transcranial direct current stimulation on perception and pain thresholds in healthy volunteers

Background and purpose: We aimed to evaluate whether transcranial direct current stimulation (tDCS) is effective in modulating sensory and pain perception thresholds in healthy subjects as to further explore mechanisms of tDCS in pain relief. Methods: Twenty healthy subjects received stimulation with tDCS under four different conditions of stimulation: anodal tDCS of the primary motor cortex (M1), dorsolateral prefrontal cortex (DLPFC), occipital cortex (V1), and sham tDCS. The order of conditions was randomized and counterbalanced across subjects. Perception threshold and pain threshold to peripheral electrical stimulation of the right index finger were evaluated by a blinded rater. Results: The results showed a significant effect of the interaction time versus stimulation condition for perception (P = 0.046) and pain threshold (P = 0.015). Post hoc comparisons revealed that anodal stimulation of M1 increased both perception (P < 0.001, threshold increase of 6.5%) and pain (P = 0.001, threshold increase of 8.3%) thresholds significantly, whilst stimulation of the DLPFC increased pain threshold only (P = 0.046, threshold increase of 10.0%). There were no significant effects for occipital or sham stimulation. Conclusions: These results show that both M1 and DLFPC anodal tDCS can be used to modulate pain thresholds in healthy subjects; thus, the mechanism of tDCS in modulating pain involves pathways that are independent of abnormal pain‐related neural activity.     

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.     

Alternate sessions of transcranial direct current stimulation (tDCS) reduce chronic pain in women affected by chikungunya. A randomized clinical trial

ContextThousands of people worldwide have been infected by the chikungunya virus (CHIKV), and the persistence of joint pain symptoms has been considered the main problem. Neuromodulation techniques such as transcranial direct current stimulation (tDCS) act on brain areas involved in the processing of chronic pain. It was previously demonstrated that tDCS for five consecutive days significantly reduced pain in the chronic phase of chikungunya (CHIK).ObjectiveTo analyze the effect of alternate tDCS sessions on pain and functional capacity in individuals affected by CHIK.MethodsIn a randomized clinical trial, 58 women in the chronic phase of CHIK were divided into two groups: active-tDCS (M1-S0, 2 mA, 20 min) and sham-tDCS. The Visual Analogue Scale (VAS) and the Brief Pain Inventory (BPI) were used to assess pain, while the Health Assessment Questionnaire (HAQ) assessed functional capacity. These scales were used before and after six sessions of tDCS in nonconsecutive days on the primary motor cortex, and at follow-up consultation 7 and 15 days after the last session. A repeated measures mixed-model ANOVA was used for comparison between groups (significant p-values < 0.05).ResultsA significant pain reduction (Z [3, 171] = 14.303; p < 0.0001) was observed in the tDCS group compared to the sham group; no significant difference in functional capacity was observed (Z [1.57] = 2.797; p = 0.1).ConclusionOur results suggest that six nonconsecutive sessions of active tDCS on M1 reduce pain in chronic CHIKV arthralgia.     

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.     

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.     

Modulation of moving phosphene thresholds by transcranial direct current stimulation of V1 in human

Small moving sensations, so-called moving phosphenes are perceived, when V5, a visual area important for visual motion analysis, is stimulated by transcranial magnetic stimulation (TMS). However, it is still a matter of debate if only V5 takes part in movement perception or other visual areas are also involved in this process. In this study we tested the involvement of V1 in the perception of moving phosphenes by applying transcranial direct current stimulation (tDCS) to this area. tDCS is a non-invasive stimulation technique known to modulate cortical excitability in a polarity-specific manner. Moving and stationary phosphene thresholds (PT) were measured by TMS before, immediately after and 10, 20 and 30 min after the end of 10 min cathodal and anodal tDCS in nine healthy subjects. Reduced PTs were detected immediately and 10 min after the end of anodal tDCS while cathodal stimulation resulted in an opposite effect. Our results show that the excitability shifts induced by V1 stimulation can modulate moving phosphene perception. tDCS elicits transient, but yet reversible effects, thus presenting a promising tool for neuroplasticity research.     

Randomized clinical trial comparing of transcranial direct current stimulation (tDCS) and transcutaneous electrical nerve stimulation (TENS) in knee osteoarthritis

BackgroundDue to the limitations of pharmacological and surgical management of knee osteoarthritis (OA), several non-pharmacologic approaches including transcutaneous electrical nerve stimulation (TENS) and transcranial direct current stimulation (tDCS) have been introduced, with promising results.ObjectiveWe aimed to investigate and compare the therapeutic effects of TENS and tDCS for the treatment of patients with knee OA.MethodsIn this double-blinded randomized controlled trial, a total of 40 adult patients with knee OA were randomly allocated to either the TENS or the tDCS group. Patients in either group received 6 sessions of the TENS or tDCS for 2 weeks. Knee strengthening exercises were performed twice daily for the entire treatment period. Patients were evaluated using the visual analogue scale (VAS) and Western Ontario and McMaster Universities (WOMAC).ResultsSignificant improvement was observed in all outcomes in both TENS and tDCS groups at each follow up compared to baseline although the early improvement (first follow-up) in the WOMAC index was not significant in the TENS group. Based on the within-subject analysis, the behavior of two treatment groups did not differ regarding the changes in the course of the VAS, WOMAC score and its subscales, i.e. stiffness, pain and function (p = 0.263, 0.051, 0.198, 0.075, and 0.146, respectively).ConclusionsBased on the results of this study, the effect of tDCS and TENS was not significantly different on pain and function of patients with knee OA.     

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).     

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 transcranial direct current stimulation on working memory in patients with Parkinson's disease

OBJECTIVES: Cognitive impairment is a common feature in Parkinson's disease (PD) and is an important predictor of quality of life. Past studies showed that some aspects of cognition, such as working memory, can be enhanced following dopaminergic therapy and transcranial magnetic stimulation. The aim of our study was to investigate whether another form of noninvasive brain stimulation, anodal transcranial direct current stimulation (tDCS), which increases cortical excitability, is associated with a change in a working memory task performance in PD patients. METHODS: We studied 18 patients (12 men and 6 women) with idiopathic PD. The patients performed a three-back working memory task during active anodal tDCS of the left dorsolateral prefrontal cortex (LDLPFC), anodal tDCS of the primary motor cortex (M1) or sham tDCS. In addition, patients underwent two different types of stimulation with different intensities: 1 and 2 mA. RESULTS: The results of this study show a significant improvement in working memory as indexed by task accuracy, after active anodal tDCS of the LDLPFC with 2 mA. The other conditions of stimulation: sham tDCS, anodal tDCS of LDLPFC with 1 mA or anodal tDCS of M1 did not result in a significant task performance change. CONCLUSION: tDCS may exert a beneficial effect on working memory in PD patients that depends on the intensity and site of stimulation. This effect might be explained by the local increase in the excitability of the dorsolateral prefrontal cortex.     

Enhancing cognitive control training with transcranial direct current stimulation: a systematic parameter study

BackgroundCognitive control (CC) is an important prerequisite for goal-directed behaviour and efficient information processing. Impaired CC is associated with reduced prefrontal cortex activity and various mental disorders, but may be effectively tackled by transcranial direct current stimulation (tDCS)-enhanced training. However, study data are inconsistent as efficacy depends on stimulation parameters whose implementations vary widely between studies.ObjectiveWe systematically tested various tDCS parameter effects (anodal/cathodal polarity, 1/2 mA stimulation intensity, left/right prefrontal cortex hemisphere) on a six-session CC training combined with tDCS.MethodsNine groups of healthy humans (male/female) received either anodal/cathodal tDCS of 1/2 mA over the left/right PFC or sham stimulation, simultaneously with a CC training (modified adaptive Paced Auditory Serial Addition Task [PASAT]). Subjects trained thrice per week (19 min each) for two weeks. We assessed performance progress in the PASAT before, during, and after training. Using a hierarchical approach, we incrementally narrowed down on optimal stimulation parameters supporting CC. Long-term CC effects as well as transfer effects in a flanker task were assessed after the training period as well as three months later.ResultsCompared to sham stimulation, anodal but not cathodal tDCS improved performance gains. This was only valid for 1 mA stimulation intensity and particularly detected when applied to the left PFC.ConclusionsOur results confirm beneficial, non-linear effects of anodal tDCS on cognitive training in a large sample of healthy subjects. The data consolidate the basis for further development of functionally targeted tDCS, supporting cognitive control training in mental disorders and guiding further development of clinical interventions.     

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.     

Significant group-level hotspots found in deep brain regions during transcranial direct current stimulation (tDCS): A computational analysis of electric fields

ObjectiveTranscranial direct current stimulation (tDCS) is a neuromodulation scheme that delivers a small current via electrodes placed on the scalp. The target is generally assumed to be under the electrode, but deep brain regions could also be involved due to the large current spread between the electrodes. This study aims to computationally evaluate if group-level hotspots exist in deep brain regions for different electrode montages.MethodsWe computed the tDCS-generated electric fields (EFs) in a group of subjects using interindividual registration methods that permitted the projection of EFs from individual realistic head models (n = 18) to a standard deep brain region.ResultsThe spatial distribution and peak values (standard deviation of 14%) of EFs varied significantly. Nevertheless, group-level EF hotspots appeared in deep brain regions. The caudate had the highest field peaks in particular for F3-F4 montage (70% of maximum cortical EF), while other regions reach field peaks of 50%.ConclusionstDCS at deeper regions may include not only modulation via underlying cortical or subcortical circuits but also modulation of deep brain regions.SignificanceThe presented EF atlas in deep brain regions can be used to explain tDCS mechanism or select the most appropriate tDCS montage.     

Modulation of cortical responses by transcranial direct current stimulation of dorsolateral prefrontal cortex: A resting-state EEG and TMS-EEG study

Background

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique with potential for cost-effective therapeutic neuromodulation. Although positive therapeutic effects were found by stimulating the dorsolateral prefrontal cortex (DLPFC), few studies have investigated physiological effects of DLPFC-tDCS.

Enhancing decision-making and cognitive impulse control with transcranial direct current stimulation (tDCS) applied over the orbitofrontal cortex (OFC): A randomized and sham-controlled exploratory study

BackgroundDecision-making and impulse control (both cognitive and motor) are complex interrelated processes which rely on a distributed neural network that includes multiple cortical and subcortical regions. Among them, the orbitofrontal cortex (OFC) seems to be particularly relevant as demonstrated by several neuropsychological and neuroimaging investigations.MethodsIn the present study we assessed whether transcranial direct current stimulation (tDCS) applied bilaterally over the OFC is able to modulate decision-making and cognitive impulse control. More specifically, 45 healthy subjects were randomized to receive a single 30-min session of active or sham anodal tDCS (1.5 mA) applied over either the left or the right OFC (coupled with contralateral cathodal tDCS). They were also assessed pre- and post-tDCS with a battery of computerized tasks.ResultsOur results show that participants who received active anodal tDCS (irrespective of laterality), vs. those who received sham tDCS, displayed more advantageous decision-making (i.e., increased Iowa Gambling Task “net scores” [p = 0.04]), as well as improved cognitive impulse control (i.e., decreased “interference” in the Stroop Word-Colour Task [p = 0.007]). However, we did not observe tDCS-related effects on mood (assessed by visual analogue scales), attentional levels (assessed by the Continuous Performance Task) or motor impulse control (assessed by the Stop-Signal Task).ConclusionsOur study potentially serves as a key translational step towards the development of novel non-invasive neuromodulation-based therapeutic interventions directly targeting vulnerability factors for psychiatric conditions such as suicidal behaviour and addiction.     

Effects of transcranial direct current stimulation coupled with repetitive electrical stimulation on cortical spreading depression

We have recently shown that two techniques of brain stimulation - repetitive electrical stimulation (ES) (that mimics transcranial magnetic stimulation) and transcranial direct current stimulation (tDCS) - modify the velocity of cortical spreading depression (CSD) significantly. Herein we aimed to study the effects of these two techniques combined on CSD. Thirty-two Wistar rats were divided into four groups according to the treatment: sham tDCS/sham ES, sham tDCS/1 Hz ES, anodal tDCS/1 Hz ES, cathodal tDCS/1 Hz ES. Our findings show that 1 Hz ES reduced CSD velocity, and this effect was modified by either anodal or cathodal tDCS. Anodal tDCS induced larger effects than cathodal tDCS. Hereby CSD velocity was actually increased significantly after anodal tDCS/1 Hz ES. Our results show that combining two techniques of brain stimulation can modify significantly the effects of ES alone on cortical excitability as measured by the neurophysiological parameter of cortical spreading depression and therefore provide important insights into the effects of this new approach of brain stimulation on cortical activity.     

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.