Placebo tDCS Research Articles

Anodal tDCS improves neuromuscular adaptations to short-term resistance training of the knee extensors in healthy individuals.

Experimental studies showed improvement in physical performance following acute application of transcranial direct current stimulation (tDCS). This study examined the neuromuscular and neural response to a single training session (Part 1) and after a 3-week resistance training (Part 2) performed with the knee extensors, preceded by tDCS over the primary motor cortex. Twenty-four participants (age, 30 ± 7 years; stature, 172 ± 8 cm; mass, 72 ± 15 kg) were randomly allocated to perform either resistance training with anodal tDCS (a-tDCS), or by a placebo tDCS (Sham). Resistance training consisted of 3 × 10 isometric contractions of 3 s at 75% MVC. Measures of neuromuscular function (MVC, voluntary activation and potentiated twitch force), corticospinal excitability, and short and long cortical inhibition were assessed. Acute tDCS did not affect neuromuscular and neural responses to a single training session (all ps ≥ 0.10). Conversely, after the 3-week training program, MVC increased in both groups (p < 0.01), with a greater increase observed for a-tDCS vs. Sham (⁓6%, p = 0.04). Additionally, increased voluntary activation (⁓2%, p = 0.04) and corticospinal excitability (⁓22%, p = 0.04), accompanied with shorter silent period (-13%, p = 0.04) was found following a-tDCS vs. Sham. The potentiated twitch force and measures of short and long cortical inhibition did not change after training programme (all ps ≥ 0.29). Pre-training administration of tDCS only resulted in greater neuromuscular adaptations following 3-weeks of resistance training. These results provide new evidence that tDCS facilitates adaptations to resistance training in healthy individuals.

Long-lasting improvements in episodic memory among subjects with mild cognitive impairment who received transcranial direct current stimulation combined with cognitive treatment and telerehabilitation: a multicentre, randomized, active-controlled study.

In recent years, an increasing number of studies have examined the potential efficacy of cognitive training procedures in individuals with normal ageing and mild cognitive impairment (MCI). The aims of this study were to (i) evaluate the efficacy of the cognitive Virtual Reality Rehabilitation System (VRRS) combined with anodal transcranial direct current stimulation (tDCS) applied to the left dorsolateral prefrontal cortex compared to placebo tDCS stimulation combined with VRRS and (ii) to determine how to prolong the beneficial effects of the treatment. A total of 109 subjects with MCI were assigned to 1 of 5 study groups in a randomized controlled trial design: (a) face-to-face (FTF) VRRS during anodal tDCS followed by cognitive telerehabilitation (TR) (clinic-atDCS-VRRS+Tele@H-VRRS); (b) FTF VRRS during placebo tDCS followed by TR (clinic-ptDCS-VRRS+Tele@H-VRRS); (c) FTF VRRS followed by cognitive TR (clinic-VRRS+Tele@H-VRRS); (d) FTF VRRS followed by at-home unstructured cognitive stimulation (clinic-VRRS+@H-UCS); and (e) FTF cognitive treatment as usual (clinic-TAU). An improvement in episodic memory was observed after the end of clinic-atDCS-VRRS (p < 0.001). We found no enhancement in episodic memory after clinic-ptDCS-VRRS or after clinic-TAU.Moreover, the combined treatment led to prolonged beneficial effects (clinic-atDCS-VRRS+Tele@H-VRRS vs. clinic-ptDCS-VRRS+Tele@H-VRRS: p = 0.047; clinic-atDCS-VRRS+Tele@H-VRRS vs. clinic-VRRS+Tele@H-VRRS: p = 0.06). The present study provides preliminary evidence supporting the use of individualized VRRS combined with anodal tDCS and cognitive telerehabilitation for cognitive rehabilitation. https://clinicaltrials.gov/study/NCT03486704?term=NCT03486704&rank=1, NCT03486704.

Influence of a placebo tDCS treatment on cybersickness and EEG-neurofeedback success

Virtual Reality (VR) serves as a modern and powerful tool within the domain of neurofeedback (NF). Users can learn how to alter their own brain activation with the help of NF, for example visual feedback. VR can help to make the training more engaging and motivating with its immersive nature. However, cybersickness (CS) poses a serious problem, as it negatively affects up to 80% of all VR users. Especially women seem to be affected. Some studies suggest positive effects of placebo interventions, so that less CS in the users can be detected. Hence, we investigated whether a transcranial direct current stimulation (tDCS) placebo intervention can influence CS symptoms in a VR-based NF training and whether CS affects NF performance. Additionally, we focused on possible sex differences in the development of CS and the NF success. For this purpose, we tested 41 healthy participants in an EEG-NF-training with sensorimotor rhythm (SMR, 12–15 Hz) upregulation and VR feedback. Half of the participants got a placebo tDCS stimulation in advance to the training and were told that the stimulation would prevent them from getting cybersick. The other half received no such treatment. Both groups underwent six NF runs to three minutes each where they were asked to follow a ball along a predefined path in the virtual environment by increasing their SMR. Results showed that women experienced significantly more CS than men regardless of whether they received a placebo intervention or not. Women were also not able to increase their SMR successfully over the six NF runs. Male participants were able to increase their SMR. Also, only participants in the non-placebo group were able to increase their SMR, not those from the placebo group. The tDCS placebo intervention had little to no effect on sickness symptoms in VR, however it hampered the ability to increase SMR power. Also, CS seems to be associated with a worse NF training outcome, especially in women. Strategies to reduce CS inducing factors in VR environments could help participants to benefit more from a VR-based NF training. This should be especially considered in vulnerable groups that are more prone to CS.

Evaluation of the effects of osteopathic manipulative treatment associated with transcranial direct current stimulation in chronic nonspecific low back pain. A protocol for a randomised controlled trial

ObjectiveThis study aimed to investigate the effects of osteopathic manipulative treatment (OMT) combined with transcranial direct current stimulation (tDCS) in individuals with chronic nonspecific low back pain (CNSLBP). MethodsThis will be a randomized controlled clinical trial of three groups with blinded evaluators and participants. The study will be conducted at the at the Rehabilitation Center of the Irmandade da Santa Casa de Misericórdia de São Paulo, São Paulo, Brazil. Participants72 participants of both sexes, with CNSLBP. InterventionParticipants will be randomly allocated into three groups, with 24 participants per group (Group 1: active tDCS + active OMT; Group 2: placebo tDCS + placebo OMT; Group 3: placebo tDCS + active OMT). Assessments will be conducted before and after the intervention protocol and 1 month after the end of the entire process. For tDCS, 10 sessions of 20 minutes over 2 weeks (5 sessions per week). OMT will be performed by an osteopath, with two consultations, one per week, before the first and sixth sessions of tDCS. Main outcome measuresThe primary outcome will be the visual analog pain scale, and the Roland Morris disability and EuroQol-5D quality of life questionnaires will be used as secondary. AnalysisThe statistical analysis will be calculated using linear mixed models and based on intention-to-treat. The level of significance will be set at α = 5%.

Transcranial direct current stimulation to reduce chronic pelvic pain in endometriosis: Phase II Randomized Controlled Clinical Trial.

It is known that various chronic pain conditions lead to maladaptive changes in the central nervous system. Endometriosis is frequently associated with chronic pelvic pain (CPP). Its sufficient treatment remains a clinical challenge. Transcranial direct current stimulation (tDCS) has been shown to be a powerful method to reduce chronic pain. Therefore, this study aimed to investigate pain reduction via anodal tDCS in patients with endometriosis and CPP. This clinical phase-II, placebo-controlled, randomized, parallel designed study included 36 patients with endometriosis and CPP. All patients suffered from CPP defined as ≥ 3/10 on the visual analog scale (VAS) for ≥3 month in the past six months. Anodal or placebo tDCS (18 patients per arm) was applied over the primary motor cortex for 10 days. Primary outcome measure was pressure pain threshold (objective pain measure) as well as secondary outcomes were numerical rating scale (NRS, subjective pain measure), Von-Frey-monofilaments, and disease- and pain-related questionnaires. Data was collected at baseline, after the 10-day stimulation and at a follow-up session, which took place one week after ending tDCS. Statistical analyses were performed using ANOVA and t-tests. Significant decreased pain perception in both pain measurements: i) pressure pain threshold and ii) NRS were found for the active tDCS group compared to the placebo group. This proof-of-concept study shows that tDCS is a helpful/supporting pain therapy for patients with endometriosis and CPP. Moreover, further analyses revealed that one week after finishing the stimulation, pain reduction remained significantly decreased as indexed by pressure pain threshold indicating possible long-term analgesic effects. The present study provides evidence that tDCS is an effective therapy for pain reduction in endometriosis-associated CPP. The results found support the notion that CPP is developed and maintained in the central nervous system making a multimodal pain therapy necessary. NCT05231239.

Home-based transcranial direct current stimulation in mild neurocognitive disorder due to possible Alzheimer's disease. A randomised, single-blind, controlled-placebo study.

Mild neurocognitive disorder (mNCD), a pre-dementia stage close to Mild Cognitive Impairment, shows a progressive and constant decline in the memory domain. Of the non-pharmacological therapeutic interventions that may help to decelerate the neurodegenerative progress, transcranial direct current stimulation (tDCS) shows beneficial effects on the learning curve, immediate recall, immediate verbal memory and executive functions. The purpose of this research was to study the effect of tDCS on general cognition, immediate and delayed memory and executive functions by comparing an active group with a placebo group of mNCD patients. Participants were 33 mNCD due to possible AD, randomly assigned to two groups: 17 active tDCS and 16 placebo tDCS. Ten sessions of tDCS were conducted over the left dorsolateral prefrontal cortex. Several neuropsychological scales were administered to assess the primary outcome measures of general cognitive function, immediate and delayed memory and learning ability, whereas the secondary outcome measures included executive function tests. All participants were evaluated at baseline and at the end of the intervention. Mixed ANOVAs were performed. Significant effects were obtained on general cognitive function, immediate and delayed memory and learning ability, with increases in scores in the active tDCS group. However, there were no significant effects on executive function performance. The present study demonstrated the effectiveness of tDCS in an active tDCS group, compared to a placebo group, in improving general cognition and immediate and delayed memory, as previous studies found. Taken together, our data suggest that tDCS is a simple, painless, reproducible and easy technique that is useful for treating cognitive alterations found in neurodegenerative diseases.

Limited Add-On Effects of Unilateral and Bilateral Transcranial Direct Current Stimulation on Visuo-Motor Grip Force Tracking Task Training Outcome in Chronic Stroke. A Randomized Controlled Trial

Background: This randomized controlled trial investigated if uni- and bihemispheric transcranial direct current stimulation (tDCS) of the motor cortex can enhance the effects of visuo-motor grip force tracking task training and transfer to clinical assessments of upper extremity motor function.Methods: In a randomized, double-blind, sham-controlled trial, 40 chronic stroke patients underwent 5 days of visuo-motor grip force tracking task training of the paretic hand with either unilateral or bilateral (N = 15/group) or placebo tDCS (N = 10). Immediate and long-term (3 months) effects on training outcome and motor recovery (Upper Extremity Fugl-Meyer, UE-FM, Wolf Motor Function Test, and WMFT) were investigated.Results: Trained task performance significantly improved independently of tDCS in a curvilinear fashion. In the anodal stimulation group UE-FM scores were higher than in the sham group at day 5 (adjusted mean difference: 2.6, 95%CI: 0.6–4.5, p = 0.010) and at 3 months follow up (adjusted mean difference: 2.8, 95%CI: 0.8–4.7, p = 0.006). Neither training alone, nor the combination of training and tDCS improved WMFT performance.Conclusions: Visuo-motor grip force tracking task training can facilitate recovery of upper extremity function. Only minimal add-on effects of anodal but not dual tDCS were observed.Clinical Trial Registration: https://clinicaltrials.gov/ct2/results?recrs=&cond=&term=NCT01969097&cntry=&state=&city=&dist=, identifier: NCT01969097, retrospectively registered on 25/10/2013.

Effect of anodal high-definition transcranial direct current stimulation on the pain sensitivity in a healthy population: a double-blind, sham-controlled study.

High-definition transcranial direct current stimulation (HD-tDCS) of brain areas related to pain processing may provide analgesic effects evident in the sensory detection and pain thresholds. The somatosensory sensitivity was assessed after HD-tDCS targeting the primary motor cortex (M1) and/or the dorsolateral prefrontal cortex (DLPFC). Eighty-one (40 females) subjects were randomly assigned to 1 of 4 anodal HD-tDCS protocols (20 minutes) applied on 3 consecutive days: Sham-tDCS, DLPFC-tDCS, M1-tDCS, and DLPFC&M1-tDCS (simultaneous transcranial direct current stimulation [tDCS] of DLPFC and M1). Subjects and experimenter were blinded to the tDCS protocols. The somatosensory sensitivity were assessed each day, before and after each tDCS by detection and pain thresholds to thermal and mechanical skin stimulation, vibration detection thresholds, and pressure pain thresholds. Subjects were effectively blinded to the protocol, with no significant difference in rates of whether they received real or placebo tDCS between the 4 groups. Compared with the Sham-tDCS, none of the active HD-tDCS protocols caused significant changes in detection or pain thresholds. Independent of tDCS protocols, pain and detection thresholds except vibration detection were increased immediately after the first tDCS protocol compared with baseline (P < 0.05). Overall, the active stimulation protocols were not able to induce significant modulation of the somatosensory thresholds in this healthy population compared with sham-tDCS. Unrelated to the HD-tDCS protocol, a decreased sensitivity was found after the first intervention, indicating a placebo effect or possible habituation to the quantitative sensory testing assessments. These findings add to the increasing literature of null findings in the modulatory effects of HD-tDCS on the healthy somatosensory system.

Does transcranial direct current stimulation affect selective visual attention in children with left-sided infantile hemiplegia? A randomized, controlled pilot study

AbstractObjective:Infantile hemiplegia due to brain injury is associated with poor attention span, which critically affects the learning and acquisition of new skills, especially among children with left-sided infantile hemiplegia (LSIH). This study aimed to improve the selective visual attention (SVA) of children with LSIH through transcranial direct current stimulation (tDCS).Methods:A total of 15 children participated in this randomized, double-blinded, pilot study; of them, 10 experienced LSIH, and the remaining 5 were healthy age-matched controls. All the children performed the Computerized Stroop Color-Word Test (CSCWT) at baseline, during the 5th and 10th treatment sessions, and at follow-up. The experimental (n= 5) and control groups (n= 5) received tDCS, while the sham group (n= 5) received placebo tDCS. All three groups received cognitive training on alternate days, for 3 weeks, with the aim to improve SVA.Results:Two-way repeated measures analysis of variance (ANOVA) showed a statistically significant change in the mean scores of CSCWT between time points (baseline, 5th and 10th sessions, and follow-up) within-subject factor, group (experimental, sham) between-subject factor and interaction (time points X group) (p&lt; 0.005). Furthermore, a one-way repeated measures ANOVA showed significant differences between time point (p&lt; 0.005) for the experimental and control group but not the sham group.Conclusion:These pilot results suggest that future research should be conducted with adequate samples to enable conclusions to be drawn.

Can accelerated transcranial direct current stimulation improve memory functions? An experimental, placebo-controlled study

The aim of this study was to investigate whether transcranial Direct Current Stimulation (tDCS) could improve verbal memory functions in healthy old and younger participants. We hypothesized that active tDCS led to significantly improved memory function, compared to placebo tDCS. Forty healthy participants (20 old and 20 younger participants) were included in the study. We applied a novel stimulation protocol, where six sessions of anodal tDCS were administrated during two consecutive days. Each tDCS session lasted 30 min. The current intensity was 2mA and the stimulation area was the left temporal lobe at T3 in the 10–20 EEG system. Immediate recall, delayed recall and recognition memory were assessed with California Verbal Learning Test II (CVLT-II) and executive functions were assessed with the Trail Making Test (TMT) before the first tDCS session and after the last tDCS session. Half of the participants received placebo tDCS, whereas the other half received active tDCS. We did not reveal any significant differences between active and placebo tDCS in memory functions. However, there was a significant difference between active and placebo tDCS in executive function measured by the Trail Making Test (TMT). This experimental study failed to reveal significant differences between active and placebo accelerated tDCS for verbal memory functions. However, accelerated tDCS was found to be well-tolerated in this study.

Transcranial Direct Current Stimulation over the Left Dorsolateral Prefrontal Cortex Improves Inhibitory Control and Endurance Performance in Healthy Individuals

The dorsolateral prefrontal cortex (DLPFC) is a crucial brain region for inhibitory control, an executive function essential for behavioral self-regulation. Recently, inhibitory control has been shown to be important for endurance performance. Improvement in inhibitory control was found following transcranial direct current stimulation (tDCS) applied over the left DLPFC (L-DLPFC). This study examined the effect tDCS on both an inhibitory control and endurance performance in a group of healthy individuals. Twelve participants received either real tDCS (Real-tDCS) or placebo tDCS (Sham-tDCS) in randomized order. The anodal electrode was placed over the L-DLPFC while the cathodal electrode was placed above Fp2. Stimulation lasted 30min with current intensity set at 2mA. A Stroop test was administered to assess inhibitory control. Heart rate (HR), ratings of perceived exertion (RPE), and leg muscle pain (PAIN) were monitored during the cycling time to exhaustion (TTE) test, while blood lactate accumulation (∆B[La−]) was measured at exhaustion. Stroop task performance was improved after Real-tDCS as demonstrated by a lower number of errors for incongruent stimuli (p=0.012). TTE was significantly longer following Real-tDCS compared to Sham-tDCS (p=0.029, 17±8 vs 15±8min), with significantly lower HR (p=0.002) and RPE (p<0.001), while no significant difference was found for PAIN (p>0.224). ∆B[La−] was significantly higher at exhaustion in Real-tDCS (p=0.040). Our findings provide preliminary evidence that tDCS with the anodal electrode over the L-DLPFC can improve both inhibitory control and endurance cycling performance in healthy individuals.

Consecutive sessions of transcranial direct current stimulation do not remediate visual hallucinations in Lewy body dementia: a randomised controlled trial

BackgroundComplex visual hallucinations are common in Lewy body dementia (LBD) and can cause significant patient and caregiver distress. Current treatments are primarily pharmacological in nature and have limited efficacy and associated side effects. The objective of this study was to assess the effects of consecutive sessions of transcranial direct current stimulation (tDCS) on visual hallucination frequency and severity in LBD, at short-term and long-term follow-up stages.MethodsThe study was a randomised, double-blind, placebo-controlled trial involving 40 participants with LBD (Mage = 75.52 years, SDage = 8.69 years) which was conducted at a single site between November 2013 and December 2017. Participants received two consecutive 20-min sessions of active (0.048 mA/cm2) or placebo tDCS, separated by a 30-min break, over 5 consecutive days. The anodal electrode was applied to the right parietal cortex (P4) and the cathodal electrode was applied to the occipital cortex (Oz). The primary outcome measure was the Neuropsychiatric Inventory (NPI) hallucinations subscale, as completed by a caregiver/informant at baseline and day 5 (short-term) follow-up, and month 1 and month 3 (long-term) follow-up. Secondary outcome measures included visual cortical excitability, as measured using transcranial magnetic stimulation, computerised attentional and visuoperceptual tasks, and measures of global cognition and cognitive fluctuations.ResultsComplete study data were obtained from 36 participants. There was an overall improvement in visual hallucinations (NPI) for both groups at day 5 relative to baseline, with a medium-to-large effect size; however, compared to placebo, active tDCS did not result in any improvements in visual hallucinations (NPI) at day 5 relative to baseline, or at month 1 or month 3 follow-up time points. Additionally, comparisons of secondary outcome measures showed that active tDCS did not result in any improvements on any measure (visual cortical excitability, attentional and visuoperceptual tasks or cognitive measures) at any time point.ConclusionsRepeated consecutive sessions of parietal anodal tDCS, and occipital cathodal tDCS, do not improve visual hallucinations or visuoperceptual function, or alter visual cortical excitability in LBD.Trial registrationISRCTN, ISRCTN40214749. Registered on 25 October 2013.

Effects of Transcranial Direct Current Stimulation on Psychophysiological Responses to Maximal Incremental Exercise Test in Recreational Endurance Runners.

Previous studies have suggested that transcranial direct current stimulation (tDCS) might improve exercise performance and alter psychophysiological responses to exercise. However, it is presently unknown whether this simple technique has similar (or greater) effects on running performance. The purpose of this study was, therefore, to test the hypothesis that, compared with sham and cathodal tDCS, anodal tDCS applied over the M1 region would attenuate perception of effort, improve affective valence, and enhance exercise tolerance, regardless of changes in physiological responses, during maximal incremental exercise. In a double-blind, randomized, counterbalanced design, 13 healthy recreational endurance runners, aged 20–42 years, volunteered to participate in this study. On three separate occasions, the subjects performed an incremental ramp exercise test from rest to volitional exhaustion on a motor-driven treadmill following 20-min of brain stimulation with either placebo tDCS (sham) or real tDCS (cathodal and anodal). Breath-by-breath pulmonary gas exchange and ventilation and indices of muscle hemodynamics and oxygenation were collected continuously during the ramp exercise test. Ratings of perceived exertion (RPE) and affective valence in response to the ramp exercise test were also measured. Compared with sham, neither anodal tDCS nor cathodal tDCS altered the physiological responses to exercise (P > 0.05). Similarly, RPE and affective responses during the incremental ramp exercise test did not differ between the three experimental conditions at any time (P > 0.05). The exercise tolerance was also not significantly different following brain stimulation with either sham (533 ± 46 s) or real tDCS (anodal tDCS: 530 ± 44 s, and cathodal tDCS: 537 ± 40 s; P > 0.05). These results demonstrate that acute tDCS applied over the M1 region did not alter physiological responses, perceived exertion, affective valence, or exercise performance in recreational endurance runners.

F155. THE NEUROPHYSIOLOGICAL AND BEHAVIOURAL EFFECTS OF TRANSCRANIAL DIRECT CURRENT STIMULATION ON WORKING MEMORY AND EXECUTIVE FUNCTIONING IN SCHIZOPHRENIA

BackgroundIndividuals with schizophrenia typically suffer a range of cognitive deficits, including in executive functioning (EF) and working memory (WM) [1,2]. Such difficulties are strongly predictive of functional outcomes, but there is a lack of effective therapeutic interventions [3].Transcranial direct current stimulation (tDCS) is a novel neuromodulatory technique with emerging evidence of potential pro-cognitive applications; however there has been a dearth of understanding of mechanistic effects of this intervention [4].The aim of this study was to evaluate the neurophysiological effects of tDCS during WM and EF assessment in individuals with schizophrenia.MethodsWe utilized functional magnetic resonance imaging (fMRI) to evaluate the impact of tDCS on WM and EF in individuals with schizophrenia, randomized to receive either ‘real’ or ‘sham’ (placebo tDCS). Participants completed a WM (blocked 0–3 back) and an EF (color-word Stroop) during 30 min of 2mA tDCS applied to Broadman area 10/46 (anode 35cm2); with cathode placed on right supraorbita. Sham stimulation was applied for 30 sec. tDCS was applied during fMRI (online) [5].In addition to whole brain, we also conducted task relevant region of interest analysis (ROI) to compare mean frontal and prefrontal (Broadman are 10/46 mask) and anterior cingulate cortex (ACC) activity between the two groups during tDCS. All analyses were restricted a p-value of 0.05, following family wise-error correction (FWE).ResultsThere were no between-group differences in socio-demographic or clinical characteristics (Tab 1.) Participants did not differ on WM task performance during online tDCS (Tab 2). However, there were significant between-group differences in manipulation of information with the real tDCS performing significantly better than sham, controlled for baseline (b=0.68, CI 0.14 - 1.21; p=0.044) after consolidation [6].During WM the ROI analysis demonstrated increased activation underneath the site of the anode in the medial frontal gyrus in the real tDCS group, as compared to sham. There was a positive correlation between with consolidated performance and the activity in the medial frontal gyrus.Further, tDCS demonstrated significantly reduced activation in the left cerebellum.During EF task, increased performance was associated with decreased activity in the ACC [5].DiscussionThis is the first tDCS study to examine the brain activity during WM and EF assessment in individuals with schizophrenia using fMRIThis data suggests that biasing the membrane potential of neuronal populations in the frontal cortex seems to improve their response to other inputs i.e. decreased BOLD activation in the WM and EF network. Although the mechanism of action of tDCS is not clear yet [6], one may speculate that if the BOLD response represents synaptic activity [7], including input from other areas, then tDCS might increase the probability that a synaptic input will generate a response in an output neuron, without the need of any additional energy expended by the cell. tDCS offers a potential new therapeutic approach to the treatment of cognitive deficits.

Bilateral extracephalic transcranial direct current stimulation improves endurance performance in healthy individuals

BackgroundTranscranial direct current stimulation (tDCS) has been used to enhance endurance performance but its precise mechanisms and effects remain unknown. ObjectiveTo investigate the effect of bilateral tDCS on neuromuscular function and performance during a cycling time to task failure (TTF) test. MethodsTwelve participants in randomized order received a placebo tDCS (SHAM) or real tDCS with two cathodes (CATHODAL) or two anodes (ANODAL) over bilateral motor cortices and the opposite electrode pair over the ipsilateral shoulders. Each session lasted 10 min and current was set at 2 mA. Neuromuscular assessment was performed before and after tDCS and was followed by a cycling time to task failure (TTF) test. Heart rate (HR), ratings of perceived exertion (RPE), leg muscle pain (PAIN) and blood lactate accumulation (ΔB[La−]) in response to the cycling TTF test were measured. ResultsCorticospinal excitability increased in the ANODAL condition (P < 0.001) while none of the other neuromuscular parameters showed any change. Neuromuscular parameters did not change in the SHAM and CATHODAL conditions. TTF was significantly longer in the ANODAL (P = 0.003) compared to CATHODAL and SHAM conditions (12.61 ± 4.65 min; 10.61 ± 4.34 min; 10.21 ± 3.47 min respectively), with significantly lower RPE and higher ΔB[La−] (P < 0.001). No differences between conditions were found for HR (P = 0.803) and PAIN during the cycling TTF test (P = 0.305). ConclusionOur findings demonstrate that tDCS with the anode over both motor cortices using a bilateral extracephalic reference improves endurance performance.

P278 Transcranial direct current stimulation (tDCS) as treatment for major depression (DepressionDC) – Objectives and design of a prospective multicenter double blind randomized placebo controlled trial

Objectives Transcranial Direct Current Stimulation (tDCS) is considered as a putative therapeutical approach in Major Depressive Disorder (MDD) allowing for a non-invasive modulation of dysregulated frontal activity (Kalu et al., 2012). Findings of the largest 2 × 2 factorial randomized controlled trial (RCT) in MDD to date suggest an antidepressant effect of tDCS combined with a Selective Serotonin Reuptake Inhibitor (SSRI; Sertraline) that is superior to placebo treatment, tDCS alone and sertraline alone (Brunoni et al., 2013). With regard to a possible introduction of tDCS as treatment option for MDD a methodological sound replication trial is needed. Moreover, this study should overcome limitations of the previous trial (2 × 2 factorial design with small sample size; short treatment period; monocentre study). Methods In this randomized, placebo-controlled multicenter trial patients with MDD receive a 6-weeks treatment with prefrontal tDCS (anode over electrode position F3, cathode over F4, 5 sessions/week for 4 weeks followed by 2 sessions/week for 2 weeks, 30 min/day, 2 mA intensity) or sham tDCS (frequency and duration correspondent to active tDCS, ramp in and ramp out only without intermittent stimulation), as adjunctive treatment with a SSRI. Follow-up per patient is 3 and 6 months after the last tDCS session. Before, during, and after the treatment period different assessment scales will be conducted using a tablet-PC program which is specifically designed for this study to record neuropsychological features and the course of the individual symptomatology. Additionally, patients receive optional investigations including functional magnetic resonance imaging (fMRI) measuring functional and structural connectivity at baseline, after 6 weeks of tDCS treatment and 12 weeks after the last tDCS session. Discussion The purpose of this study is to explore the sustained efficacy and tolerability of repeated tDCS for the treatment of MDD and to assess the long-term efficacy of tDCS over 3–6 months. It is hypothesized that prefrontal tDCS in combination with an SSRI will provoke an antidepressant effect while antidepressant medication alone (sham tDCS) did not. This will be measured by the change from baseline in the Montgomery-Asberg Depression Rating Scale scores after 6 weeks of treatment.

Gender differences in cognitive Theory of Mind revealed by transcranial direct current stimulation on medial prefrontal cortex

Gender differences in social cognition are a long discussed issue, in particular those concerning Theory of Mind (ToM), i.e., the ability to explain and predict other people’s mental states. The aim of this randomized, double-blind, placebo-controlled study was to test the hypothesis that anodal tDCS over the medial prefrontal cortex (mPFC) selectively enhances cognitive ToM performance in females. In the first experiment we administered to sixteen females and sixteen males a cognitive ToM task during anodal or placebo tDCS over the mPFC. In the second experiment further sixteen females completed the task receiving anodal or placebo tDCS over the vertex. The results showed that anodal tDCS over the mPFC enhances ToM in females but not in males, an effect indicated by enhanced ToM in females that received anodal tDCS over the mPFC compared with females that received tDCS over the vertex. These findings are relevant for three reasons. First, we found evidence of gender-related differences in cognitive ToM, extending previous findings concerning affective ToM. Second, these differences emerge with anodal stimulation of the mPFC, confirming the crucial role of this area in cognitive ToM. Third, we show that taking into account gender-related differences is mandatory for the investigation of ToM.

Transcranial Direct Current Stimulation in Mesial Temporal Lobe Epilepsy and Hippocampal Sclerosis.

Transcranial direct current stimulation (tDCS) has been evaluated in medication refractory epilepsy patients. The results have been inconclusive and protocols have varied between studies. To evaluate the safety and efficacy of two protocols of tDCS in adult patients with mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE-HS). This is a randomized placebo-controlled, double-blinded clinical trial, with 3 arms, 3 sessions, 5 sessions and placebo stimulation. Frequency of seizures (SZs), interictal epileptiform discharges (IEDs) and adverse effects (AEs) were registered before and after treatment, and at 30 and 60 days follow-up. Descriptive statistics, k-related samples, Friedman's test, and relative risk (RR) estimation were used for analysis. We included twenty-eight subjects (3d n = 12, 5d n = 8, placebo n = 8), 16/28 (57%) men, age 37.8(±10.9) years old. There was a significant reduction of the frequency of SZs at one (p = 0.001) and two (p = 0.0001) months following cathodal tDCS compared to baseline in the 3 arms (p = 0.0001). The mean reduction of SZ frequency at two months in both active groups was significantly higher than placebo (-48% vs. -6.25%, p < 0.008). At 3 days (-43.4% vs. -6.25%, p < 0.007) and 5 days (-54.6% vs. -6.25%, p < 0.010) individual groups showed a greater reduction of SZs. A significant IED reduction effect was found between baseline and immediately after interventions (p = 0.041) in all groups. Side effects were minor. Cathodal tDCS technique of 3 and 5 sessions decreased the frequency of SZs and IEDs (between baseline and immediately post-tDCS) in adult patients with MTLE-HS compared to placebo tDCS.

Older adults get episodic memory boosting from noninvasive stimulation of prefrontal cortex during learning

Episodic memory displays the largest degree of age-related decline, a process that is accelerated in pathological conditions such as amnestic mild cognitive impairment and Alzheimer's disease. Previous studies have shown that the left lateral prefrontal cortex (PFC) contributes to the encoding of episodic memories along the life span. The aim of this randomized, double-blind, placebo-controlled study was to test the hypothesis that anodal trascranial direct current stimulation (tDCS) over the left lateral PFC during the learning phase would enhance delayed recall of verbal episodic memories in elderly individuals. Older adults learned a list of words while receiving anodal or placebo (sham) tDCS. Memory recall was tested 48 hours and 1 month later. The results showed that anodal tDCS strengthened episodic memories, an effect indicated by enhanced delayed recall (48 hours) compared to placebo stimulation (Cohen's d effect size = 1.01). The observation that PFC-tDCS during learning can boost verbal episodic memory in the elderly opens up the possibility to design-specific neurorehabilitation protocols targeted to conditions that affect episodic memory such as mild cognitive impairment.

Left parietal cortex transcranial direct current stimulation enhances gesture processing in corticobasal syndrome

Corticobasal syndrome (CBS) is a clinical entity characterized by higher cortical dysfunctions associated with asymmetric onset of levodopa-resistant parkinsonism, dystonia and myoclonus. One of the most typical and distressful features of CBS is limb apraxia, which affects patients in their everyday life. Transcranial direct current stimulation (tDCS) is a non-invasive procedure of cortical stimulation, which represents a promising tool for cognitive enhancement and neurorehabilitation. The present study investigated whether anodal tDCS over the parietal cortex (PARC), would improve ideomotor upper limb apraxia in CBS patients. Fourteen patients with possible CBS and upper limb apraxia were enrolled. Each patient underwent two sessions of anodal tDCS (left and right PARC) and one session of placebo tDCS. Ideomotor upper limb apraxia was assessed using the De Renzi ideomotor apraxia test that is performed only on imitation. A significant improvement of the De Renzi ideomotor apraxia test scores (post-stimulation versus pre-stimulation) after active anodal stimulation over the left PARC was observed (χ(2) = 17.6, P = 0.0005), whilst no significant effect was noticed after active anodal stimulation over the right PARC (χ(2) = 7.2, P = 0.07). A post hoc analysis revealed a selective improvement in the De Renzi ideomotor apraxia score after active anodal stimulation over the left PARC compared with placebo stimulation considering both right (P = 0.03) and left upper limbs (P = 0.01). These findings indicate that tDCS to the PARC improves the performance of an ideomotor apraxia test in CBS patients and might represent a promising tool for future rehabilitation approaches.