Transcranial direct current stimulation for depression in Alzheimer\u2019s disease: study protocol for a randomized controlled trial

Background:Transcranial direct current stimulation over the dorsolateral prefrontal cortex has been shown to be clinically useful in the treatment of drug addiction.Methods:We conducted a double-blind randomized clinical trial aiming to assess the effects of bilateral dorsolateral prefrontal cortex transcranial direct current stimulation (left cathodal/right anodal) on crack-cocaine addiction. We defined craving as the primary outcome, and other clinical measurements, including depressive and anxiety symtoms, and quality of life, as secondary outcomes. Seventeen male crack-cocaine users (mean age 30.4±9.8 SD) were randomized to receive 5 sessions of active transcranial direct current stimulation (2 mA, 35cm2, for 20 minutes), every other day, and 19 males (mean age 30.3±8.4 SD) to receive sham-transcranial direct current stimulation (placebo) as control group.Results:Craving scores were significantly reduced in the transcranial direct current stimulation group after treatment when compared with sham-transcranial direct current stimulation (P=.028) and baseline values (P=.003), and decreased linearly over 4 weeks (before, during, and after treatment) in the transcranial direct current stimulation group only (P=.047). Changes of anxiety scores towards increase in the sham-transcranial direct current stimulation and decrease in the transcranial direct current stimulation group (P=.03), and of the overall perception of quality of life (P=.031) and of health (P=.048) towards decrease in the sham-transcranial direct current stimulation group and increase in the transcranial direct current stimulation group differed significantly between groups.Conclusions:Repetitive bilateral transcranial direct current stimulation over the dorsolateral prefrontal cortex reduced craving for crack-cocaine use, decreased anxiety, and improved quality of life. We hypothesize that transcranial direct current stimulation effects may be associated with increased prefrontal processing and regulation of craving behavior.

To explore the effects of transcranial direct current stimulation followed by treadmill training on dual-task gait performance and contralesional cortical activity in chronic stroke patients. Forty-five chronic stroke participants were randomized into 3 groups: a bilateral transcranial direct current stimulation and treadmill training group; a cathodal transcranial direct current stimulation and treadmill training group; and a sham transcranial direct current stimulation and treadmill training group for 50 min per session (20 min transcranial direct current stimulation followed by 30 min treadmill training), 3 sessions per week for 4 weeks. Outcome measures included cognitive dual-task walking, motor dual-task walking, walking performance, contralesional cortical activity, and lower-extremity motor control. The cathodal transcranial direct current stimulation + treadmill training group showed significantly greater improvements in cognitive dual-task walking speed than the other groups (p cathodal vs sham = 0.006, p cathodal vs bilateral = 0.016). In the cathodal transcranial direct current stimulation + treadmill training group the silent period duration increased significantly more than in the other groups (p < 0.05). Changes in motor evoked potentials in the cathodal transcranial direct current stimulation + treadmill training group were greater than those in the sham transcranial direct current stimulation + treadmill training group (p < 0.05). No significant changes were observed in the bilateral transcranial direct current stimulation + treadmill training group. Cathodal transcranial direct current stimulation followed by treadmill training is an effective intervention for improving cognitive dual-task walking and modulating contralesional cortical activity in chronic stroke. No beneficial effects were observed after bilateral transcranial direct current stimulation and treadmill training.

Background/Aims Children with hemiplegic cerebral palsy have limitations in activities requiring reach and manipulation of objects with their affected upper extremity. Transcranial direct current stimulation and the cognitive orientation to occupational performance approach are relatively new interventions that may lead to promising results for these children. This article describes the method of a randomised clinical trial that will compare the effects of the combination of transcranial direct current stimulation and cognitive orientation to daily occupational performance with transcranial direct current stimulation and neurodevelopmental treatment. Methods A four-armed clinical trial with a sample size of 36 participants will be performed in Tehran. Participants will be randomly divided into four groups. Group A will receive neuro-developmental treatment with sham transcranial direct current stimulation, group B will receive neurodevelopmental treatment with transcranial direct current stimulation, group C will receive cognitive orientation to daily occupational performance with sham transcranial direct current stimulation, and group D will receive cognitive orientation to daily occupational performance with transcranial direct current stimulation. The examiner will be blind to the study and assessments will be done at baseline, after the end of the intervention and 1 month after the completion of the intervention (as follow up). Data analysis will be as repeated measure analysis of variance and intention to treat. Conclusions This article describes the protocol of a clinical trial that compares the effects of the combination of transcranial direct current stimulation and cognitive orientation to daily occupational performance with the combination of transcranial direct current stimulation and neurodevelopmental treatment on upper extremity goals and functions of children with hemiplegic cerebral palsy.

Individuals with schizophrenia typically suffer a range of cognitive deficits, including prominent deficits in working memory and executive function. These difficulties are strongly predictive of functional outcomes, but there is a paucity of effective therapeutic interventions targeting these deficits. Transcranial direct current stimulation is a novel neuromodulatory technique with emerging evidence of potential pro-cognitive effects; however, there is limited understanding of its mechanism. This was a double-blind randomized sham controlled pilot study of transcranial direct current stimulation on a working memory (n-back) and executive function (Stroop) task in 28 individuals with schizophrenia using functional magnetic resonance imaging. Study participants received 30 min of real or sham transcranial direct current stimulation applied to the left frontal cortex. The 'real' and 'sham' groups did not differ in online working memory task performance, but the transcranial direct current stimulation group demonstrated significant improvement in performance at 24 h post-transcranial direct current stimulation. Transcranial direct current stimulation was associated with increased activation in the medial frontal cortex beneath the anode; showing a positive correlation with consolidated working memory performance 24 h post-stimulation. There was reduced activation in the left cerebellum in the transcranial direct current stimulation group, with no change in the middle frontal gyrus or parietal cortices. Improved performance on the executive function task was associated with reduced activity in the anterior cingulate cortex. Transcranial direct current stimulation modulated functional activation in local task-related regions, and in more distal nodes in the network. Transcranial direct current stimulation offers a potential novel approach to altering frontal cortical activity and exerting pro-cognitive effects in schizophrenia.

Efficacy of transcranial direct-current stimulation in women with provoked vestibulodynia

BackgroundCognitive impairment after stroke is common and can cause disability with major impacts on quality of life and independence. Transcranial direct current stimulation may represent a promising tool for reconstitution of cognitive functions in stroke patients.ObjectivesThis study aimed to investigate the effect of transcranial direct current stimulation on cognitive functions in stroke patients.Patients and methodsForty male stroke patients were included. Patients were divided randomly into two equal groups (A and B). Group A received transcranial direct current stimulation (tDCS) in combination with selected cognitive training program by RehaCom. Group B received sham transcranial direct current stimulation in combination with the same cognitive training program.Cognitive evaluation and functional independence measure (FIM) were done for all patients before and after treatment.ResultsThere was a significant improvement in the scores of attention and concentration, figural memory, logical reasoning, reaction behavior, and FIM post treatment in both groups; the improvement was significantly higher in group A compared to group B.ConclusiontDCS is a safe and effective neuro-rehabilitation modality that improves post stroke cognitive dysfunctions. Moreover, tDCS has a positive impact on performance of daily activities.

Effects of transcranial direct current stimulation on hemichannel pannexin-1 and neural plasticity in rat model of cerebral infarction

Background and Objective: Transcranial Direct Current Stimulation (tDCS) may exert therapeutic effects on tinnitus. This Randomized Control Trial (RCT) with double blind and placebo design investigates the potential therapeutic effects of Transcranial Direct Current Stimulation on chronic and intractable tinnitus using a new protocol. Acute repeated sessions of bifrontal Transcranial Direct Current Stimulation with two months follow up will be used for treatment of tinnitus symptoms and comorbid anxiety and depression. To best of our knowledge, this is the first randomized control trial investigating the effects of acute Transcranial Direct Current Stimulation exposure in intractable tinnitus. Methods: This randomized control trial is conducted as double blinded placebo controlled with parallel group in patients with chronic intractable tinnitus. The patients will be randomly divided into two real or intervention and sham or placebo Transcranial Direct Current Stimulation. The real Transcranial Direct Current Stimulation group will receive two sessions per day with intersession interval of 6 hours for 5 consecutive days per week for one week (total 10 sessions). The Transcranial Direct Current Stimulation parameters include bifrontal (anode/cathode over right/left dorsolateral prefrontal cortex (DLPFC) 2 mA current (current density 57.1 μA/cm2), each session 20 min through 35 cm2 electrodes. The sham group will receive the same Transcranial Direct Current Stimulation parameters and electrode montage and after 30 seconds, the device will be turned off without informing the patient. The primary outcome is the score of Tinnitus Handicap Inventory (THI) measured at baseline (pre-intervention) and post-intervention at immediately, one, and two months after last session. The secondary outcomes are tinnitus loudness, tinnitus distress, depression, and anxiety scores. The tinnitus loudness and distress are measured with a 0-10 Numerical Rating Scale (NRS) preintervention and post-intervention at immediately, one hour, one week, one, and two months after the last Transcranial Direct Current Stimulation session. Beck Depression (BDI-II) and Anxiety Inventories (BAI) is respectively used for measuring depression and anxiety score pre- and post-intervention. Finally, the adverse effects of and tolerability to Transcranial Direct Current Stimulation will be assessed in both real and sham groups using customized questionnaire. Discussion: To the best of our knowledge this is the first RCT investigating the effects of daily two sessions of Transcranial Direct Current Stimulation in repeated regime on chronic intractable tinnitus symptoms, depression, anxiety, and adverse effects in a long term study of two months follow-up.

Correct blinding is essential for preventing potential biases. The aim of this study was to assess the blinding of participants and a therapist following treatment with transcranial direct current stimulation in subjects with fibromyalgia using James’ and Bang’s blinding indexes. Eighty subjects were randomly allocated either active or sham stimulation groups in an intervention of five sessions lasting 20 min each. A questionnaire was delivered to both the therapist and patients after the last session to record their guess of which treatment had been applied. No differences between the groups were noted at baseline in terms of demographic or clinical data. James’ BI was 0.83 (CI 95%: 0.76–0.90) for the patients and 0.55 (CI 95%: 0.45–0.64) for the therapist. Bang’s BI for subjects was −0.08 (CI 95%: −0.24–0.09) and −0.8 (CI 95%: −0.26–0.1) for the active and sham transcranial direct current stimulation groups, respectively. Bang’s BI for the therapist was 0.21 (CI 95%: −0.02–0.43) and 0.13 (CI 95%: −0.09–0.35) for the active and sham transcranial direct current stimulation groups, respectively. Protocols of active and sham transcranial direct current stimulation applied in this study have shown satisfactory blinding of the therapist and subjects with fibromyalgia.

The aim of this study was to investigate the effects of transcranial direct current stimulation (TDCS) combined with tinnitus retraining therapy (TRT) on clinical efficacy and sleep disorder in patients with chronic tinnitus. 126 patients with chronic tinnitus treated in our hospital from May 2020 to June 2022 were retrospectively analyzed. These subjects were randomly divided into two groups: the electrical stimulation group and the combined group, in line with the random table method, with 63 patients in each group. Patients in the electrical stimulation group received TDCS treatment, and patients in the combined group were given TDCS combined with TRT. The clinical effects, tinnitus severity [Tinnitus Evaluation Questionnaire (TEQ) score and Tinnitus handicap inventory (THI) score], sleep status [Sleep Status Rating Scale (SRSS) score and Pittsburgh Sleep Quality Index (PSQI) score], psychological status [Hamilton Anxiety Scale (HAMA) score and Self Rating Depression Scale (SDS) score] and the quality of life (Quality of Life Scale) of these subjects in two groups were analyzed. The clinical effect of simple TDCS was 82.53%, which was sharply lower compared to 95.24% in the combined group (p<0.05). After the treatment, TEQ score, THI score, SRSS score, PSQI score, HAMA score, and SDS score were decreased in both groups (p<0.05), and the combined group was much lower than the TDCS group (p<0.01). Compared with the pre-treatment period, the scores of restrictions in daily living, medical resource utilization, somatic symptoms, and emotional disturbance were elevated in both groups after treatment, and the combined group had markedly higher scores than the TDCS group (p<0.05). TDCS combined with TRT had obvious effects in treating chronic tinnitus, which largely reduced the severity of tinnitus, improved patients' sleep quality and psychological status, and improved the quality of life, indicating a certain worthy of clinical application and promotion.

Transcranial direct current stimulation is a painless, non-invasive brain stimulation technique that allows one to induce polarity-specific excitability changes in the human brain. Here, we investigated, for the first time in a 'proof of principle' study, the behavioural effect of transcranial direct current stimulation on visuospatial attention in both healthy controls and stroke patients suffering from left visuospatial neglect. We applied anodal, cathoP:dal or sham transcranial direct current stimulation (57 microA/cm(2), 10 min) to the left or right posterior parietal cortex. Using a visual detection task in a group of right-handed healthy individuals (n = 20), we observed that transcranial direct current stimulation enhanced or impaired performance depending on stimulation parameters (i.e. current polarity) and stimulated hemisphere. These results are in good accordance with classic models of reciprocal interhemispheric competition ('rivalry'). In a second experiment, we investigated the potential of transcranial direct current stimulation to ameliorate left visuospatial neglect (n = 10). Interestingly, both the inhibitory effect of cathodal transcranial direct current stimulation applied over the unlesioned posterior parietal cortex and the facilitatory effect of anodal transcranial direct current stimulation applied over the lesioned posterior parietal cortex reduced symptoms of visuospatial neglect. Taken together, our findings suggest that transcranial direct current stimulation applied over the posterior parietal cortex can be used to modulate visuospatial processing and that this effect is exerted by influencing interhemispheric reciprocal networks. These novel findings also suggest that a transcranial direct current stimulation-induced modulation of interhemispheric parietal balance may be used clinically to ameliorate visuospatial attention deficits in neglect patients.

To investigate the combined effect of transcranial magnetic stimulation (TMS) and transcranial direct current stimulation on improving lower limb function in stroke patients. Randomized controlled trial. Subacute stroke patients. 169 post-stroke hemiplegia patients were randomly divided into 4 groups (control, transcranial direct current stimulation, transcutaneous auricular vagus nerve stimulation, and transcutaneous auricular vagus nerve stimulation combined with transcranial direct current stimulation) and evaluated using the Fugl-Meyer Assessment-Lower Extremity (FMA-LL), Timed Up-and-Go (TUG) test, Modified Barthel Index (MBI), Berg Balance Scale (BBS), gait parameters, and surface electromyography (sEMG). Significant improvements in FMA-LL, MBI, BBS, TUG, gait parameters, and sEMG were noted in the intervention groups compared with the control, with the transcutaneous auricular vagus nerve stimulation combined with transcranial direct current stimulation group showing the most pronounced improvements. Differences in some outcomes were also notable between the transcutaneous auricular vagus nerve stimulation and transcranial direct current stimulation groups. The combination of transcutaneous auricular vagus nerve stimulation and transcranial direct current stimulation effectively enhances gait, balance, and daily living activities in subacute stroke patients. These benefits are likely due to transcutaneous auricular vagus nerve stimulation activating the solitary and trigeminal nuclei and transcranial direct current stimulation stimulating the motor cortex. Wearable gait analysis systems and electromyography are valuable in clinical gait assessment for these patients.

To determine whether transcranial direct current stimulation augments the analgesic effect of breathing-controlled electrical stimulation in patients with spinal cord injury who have chronic neuropathic pain. Sham-controlled, single-blinded, single-centre, cross-over study of 12 participants with incomplete spinal cord injury. The treatment protocol included a 20-min transcranial direct current stimulation (sham or active), followed by a 20-min breathing-controlled electrical stimulation to the median nerve on the dominant side. The treatment session with sham or control transcranial direct current stimulation was given on different days in a randomized order. Visual analogue scale was used to assess neuropathic pain at baseline, 10 min after transcranial direct current stimulation, and 10 min after breathing-controlled electrical stimulation. Participants were blinded to the status of transcranial direct current stimulation. Out of the 12 participants, 10 completed sessions of both sham and active transcranial direct current stimulation, while the other 2 completed only active transcranial direct current stimulation and breathing-controlled electrical stimulation treatment. Out of the 12 participants, 7 showed analgesic effects after active transcranial direct current stimulation, while sham transcranial direct current stimulation produced some analgesic effects in 4 out of 10 participants. At the group level, there was no difference between active and sham transcranial direct current stimulation treatment. All except one participant responded positively to breathing-controlled electrical stimulation in all sessions. Visual analogue scale score for pain decreased significantly after breathing-controlled electrical stimulation combined with either active transcranial direct current stimulation or sham transcranial direct current stimulation treatment. The immediate analgesic effect of breathing-controlled electrical stimulation was confirmed. However, this effect was not augmented after one session of transcranial direct current stimulation treatment.

The aim of the study was to investigate the effect of cathodal transcranial direct current stimulation to the supplementary motor area to inhibit involuntary movements of a child. An 8-year-old boy who developed hypoxic encephalopathy after asphyxia at the age of 2 had difficulty in remaining standing without support because of involuntary movements. He was instructed to remain standing with his plastic ankle-foot orthosis for 10 s at three time points by leaning forward with his forearms on a desk. He received cathodal or sham transcranial direct current stimulation to the supplementary motor area at 1 mA for 10 min. Involuntary movements during standing were measured using an accelerometer attached to his forehead. The low-frequency power of involuntary movements during cathodal transcranial direct current stimulation significantly decreased compared with that during sham stimulation. No adverse effects were observed. Involuntary movement reduction by cathodal stimulation to supplementary motor areas suggests that stimulations modulated the corticobasal ganglia motor circuit. Cathodal stimulation to supplementary motor areas may be effective for reducing involuntary movements and may be safely applied to children with movement disorders.

Major depressive disorder is the leading cause of mental health-related burden globally and up to one-third of major depressive disorder patients never achieve remission. Transcranial Direct Current Stimulation is a non-invasive intervention used to treat individuals diagnosed with major depressive disorder and bipolar disorder. Since the last transcranial direct current stimulation review specifically focusing on cognitive symptoms in major depressive disorder, twice as many papers have been published. A systematic review was conducted with 5 electronic databases from database inception until March 21, 2022. Randomized controlled trials with at least 1 arm evaluating transcranial direct current stimulation in adults (diagnosed with major depressive disorder or bipolar disorder using the Diagnostic and Statistical Manual of Mental Disorders or International Classification of Diseases criteria) aged 18 or older were included. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were adopted. : A total of 972 participants were included across 14 studies (60.5% female; mean age of 47.0 years [SD = 16.8]). Nine studies focused on participants with major depressive disorder and all studies used the Diagnostic and Statistical Manual of Mental Disorders to diagnose the participants. Seven out of the 14 studies showed significant improvements in at least 1 cognitive outcome measure in the active transcranial direct current stimulation group compared to the sham group. Several cognitive measures were used across studies, and 12 of the 14 studies reported mild-to-moderate side effects from treatment. : Current transcranial direct current stimulation literature has shown limited evidence for the treatment of cognitive impairments in major depressive disorder and bipolar disorder. Future research that applies machine learning algorithms may enable us to distinguish responders from non-responders, increasing clinical benefits of transcranial direct current stimulation.