Contralateral Supraorbital Area Research Articles

Transcranial Direct Current Stimulation of the Dorsolateral Prefrontal Cortex Modulates Cognitive Function Related to Motor Execution During Sequential Task: A Randomized Control Study.

In daily life, we perform a variety of sequential tasks while making cognitive decisions to achieve behavioral goals. If transcranial direct current electrical stimulation (tDCS) can be used to modulate cognitive functions involved in motor execution, it may provide a new rehabilitation method. In the present study, we constructed a new task in which cognitive decisions are reflected in motor actions and investigated whether the performance of the task can be improved by tDCS of the left dorsolateral prefrontal cortex (DLPFC). Forty healthy participants were randomly assigned to a real or sham tDCS group. The anode electrode was placed at F3 (left DLPFC), and the cathode electrode was positioned in the contralateral supraorbital area. Participants underwent one session of tDCS (1.5 mA, 20 min) and a sequential non-dominant hand task was performed for nine trials before and after tDCS. The task consisted of S1 (a manual dexterity task) and S2 (a manual dexterity task requiring a decision). The results showed the S2 trajectory length was significantly shorter after real tDCS than after sham tDCS (p = 0.017), though the S1 trajectory length was not significant. These results suggest that a single tDCS session of the left DLPFC can improve the performance of cognitive tasks complementary to motor execution, but not on dexterity tasks. By elucidating the modulating effect of tDCS on cognitive functions related to motor execution, these results may be used to improve the performance of rehabilitation patients in the future.

Neuromodulation of somatosensory pain thresholds of the neck musculature using a novel transcranial direct current stimulation montage: a randomized double-blind, sham controlled study.

Anodal transcranial direct current stimulation (tDCS) of primary motor cortex (M1) and cathodal of the primary sensory cortex (S1) have previously shown to modulate the sensory thresholds when administered with the reference electrode located over the contralateral supraorbital area (SO). Combining the two stimulation paradigms into one with simultaneous stimulation of the two brain areas (M1+S1-tDCS) may result in a synergistic effect inducing a prominent neuromodulation, noticeable in the pain thresholds. The aim of this study is to assess the efficacy of the novel M1+S1-tDCS montage compared to sham-stimulation in modulating the pain thresholds in healthy adults. Thirty-nine (20 males) subjects were randomly assigned to either receiving 20min. active M1+S1-tDCS or sham tDCS in a double-blinded single session study. Thermal and mechanical pain thresholds were assessed before and after the intervention. There were no significant differences in the pain thresholds within either group, or between the M1+S1-tDCS group and the Sham-tDCS group (p>0.05), indicating that the intervention was ineffective in inducing a neuromodulation of the somatosensory system. Experimental investigations of novel tDCS electrode montages, that are scientifically based on existing studies or computational modelling, are essential to establish better tDCS protocols. Here simultaneous transcranial direct current stimulation of the primary motor cortex and primary sensory cortex showed no effect on the pain thresholds of the neck musculature in healthy subjects. This tDCS montage may have been ineffective due to how the electrical field reaches the targeted neurons, or may have been limited by the design of a single tDCS administration. The study adds to the existing literature of the studies investigating effects of new tDCS montages with the aim of establishing novel non-invasive brain stimulation interventions for chronic neck pain rehabilitation. North Denmark Region Committee on Health Research Ethics (VN-20180085) ClinicalTrials.gov (NCT04658485).

Electrode montage-dependent intracranial variability in electric fields induced by cerebellar transcranial direct current stimulation

Transcranial direct current stimulation (tDCS) is an increasingly popular tool to investigate the involvement of the cerebellum in a variety of brain functions and pathologies. However, heterogeneity and small effect sizes remain a common issue. One potential cause may be interindividual variability of the electric fields induced by tDCS. Here, we compared electric field distributions and directions between two conventionally used electrode montages (i.e., one placing the return electrode over the ipsilateral buccinator muscle and one placing the return electrode [25 and 35 cm2 surface area, respectively] over the contralateral supraorbital area; Experiment 1) and six alternative montages (electrode size: 9 cm2; Experiment 2) targeting the right posterior cerebellar hemisphere at 2 mA. Interindividual and montage differences in the achieved maximum field strength, focality, and direction of current flow were evaluated in 20 head models and the effects of individual differences in scalp–cortex distance were examined. Results showed that while maximum field strength was comparable for all montages, focality was substantially improved for the alternative montages over inferior occipital positions. Our findings suggest that compared to several conventional montages extracerebellar electric fields are significantly reduced by placing smaller electrodes in closer vicinity of the targeted area.

Right and left inferior frontal opercula are involved in discriminating angry and sad facial expressions

BackgroundNeuroimaging studies suggest that the inferior frontal operculum (IFO) is part of a neuronal network involved in facial expression processing, but the causal role of this region in emotional face discrimination remains elusive. ObjectiveWe used cathodal (inhibitory) tDCS to test whether right (r-IFO) and left (l-IFO) IFO play a role in discriminating basic facial emotions in healthy volunteers. Specifically, we tested if the two sites are selectively involved in the processing of facial expressions conveying high or low arousal emotions. Based on the Arousal Hypothesis we expected to find a modulation of high and low arousal emotions by cathodal tDCS of the r-IFO and the l-IFO, respectively. MethodsFirst, we validated an Emotional Faces Discrimination Task (EFDT). Then, we targeted the r-IFO and the l-IFO with cathodal tDCS (i.e. the cathode was placed over the right or left IFO, while the anode was placed over the contralateral supraorbital area) during facial emotions discrimination on the EFDT. Non-active (i.e. sham) tDCS was a control condition. ResultsOverall, participants manifested the “happy face advantage”. Interestingly, tDCS to r-IFO enhanced discrimination of faces expressing anger (a high arousal emotion), whereas, tDCS to l-IFO decreased discrimination of faces expressing sadness (a low arousal emotion). ConclusionsOur findings revealed a differential causal role of r-IFO and l-IFO in the discrimination of specific high and low arousal emotions. Crucially, these results suggest that cathodal tDCS might reduce the neural noise triggered by facial emotions, improving discrimination of high arousal emotions but disrupting discrimination of low arousal emotions. These findings offer new insights for treating clinical population with deficits in processing facial expressions.

Motor cortex transcranial direct current stimulation effects on knee osteoarthritis pain in elderly subjects with dysfunctional descending pain inhibitory system: A randomized controlled trial

BackgroundAlthough evidence has indicated a positive effect of transcranial direct current stimulation (tDCS) on reducing pain, few studies have focused on the elderly population with knee osteoarthritis (KOA). ObjectiveTo evaluate whether tDCS reduces KOA pain in elderly individuals with a dysfunctional descending pain inhibitory system (DPIS). MethodsIn a double-blind trial, individuals ≥ 60 years with KOA pain and a dysfunctional DPIS, we randomly assigned patients to receive 15 daily sessions of 2 mA tDCS over the primary motor cortex (anode) and contralateral supraorbital area (cathode) (M1-SO) for 20 min or sham tDCS. Change in pain perception indexed by the Brief Pain Inventory (BPI) at the end of intervention was the primary outcome. Secondary outcomes included: disability, quantitative sensory testing, pain pressure threshold and conditioned pain modulation (CPM). Subjects were followed-up for 2 months. ResultsOf the 104 enrolled subjects, with mean (SD) age of 73.9 (8.01) years and 88 (84.6%) female, 102 finished the trial. In the intention-to-treat analysis, the active tDCS group had a significantly greater reduction in BPI compared to the sham group (difference, 1.59; 95% CI, 0.95 to 2.23; P < 0.001; Cohen’s d, 0.58); and, also a significantly greater improvement in CPM-pressure in the knee (P = 0.01) and CPM-pain in the hand (P = 0.01). These effects were not sustained at follow-up. The intervention was well tolerated, with no severe adverse effects. ConclusionM1-SO tDCS is associated with a moderate effect size in reducing pain in elderly patients with KOA after 15 daily sessions of stimulation. This intervention has also shown to modulate the DPIS.

Anodal stimulation of primary motor cortex in elderly women with fibromyalgia: A randomized, double-blind, placebo-controlled trial

It is thought that an excessive motor cortical facilitation is involved in the physiopathology of chronic pain in fibromyalgia. Studies have shown that transcranial direct current stimulation (tDCS) changes motor cortex excitability according to the stimulation polarity. Based on these effects, it is conceivable to hypothesize that tDCS, which can modulate brain activity, may induce pain relief in patients with fibromyalgia. Fifty older women with fibromyalgia were included in this randomized, doubleblind, single-center placebo controlled trial study. Patients received sham stimulation or real tDCS with the anode centered over the primary motor cortex (M1) and the cathode over the contralateral supraorbital area (2 mA for 20 minutes for 10 sessions). Pain intensity was evaluated using the visual analog scale for pain. Assessments were done before treatment and 30 days after the last session of stimulations. The mean age of participants was 58.20 years (SD = 7.80) with an age range from 55 to 74 years.Results showed no statistically significant baseline difference among patients in demographics and clinical characteristics. Comparing visual pain analogue between the sham and treatment groups revealed a statistically significant difference (p value < 0.001) for VAS immediately after intervention and 1 month post intervention between the sham and treatment groups. Analysis of data also showed a significant reduction in pain immediately after intervention and one month post-intervention in the treatment group compared to the sham group. Anodal tDCS is an effective non-invasive technique for pain reduction in elderly women with FM. The clinical improvements observed in the current study may have considerable impacts on pain experienced by elderly women with FM.

Different Effects of 2 mA and 4 mA Transcranial Direct Current Stimulation on Muscle Activity and Torque in a Maximal Isokinetic Fatigue Task.

Studies investigating the effects of transcranial direct current stimulation (tDCS) on fatigue and muscle activity have elicited measurable improvements using stimulation intensities ≤2 mA and submaximal effort tasks. The purpose of this study was to determine the effects of 2 mA and 4 mA anodal tDCS over the primary motor cortex (M1) on performance fatigability and electromyographic (EMG) activity of the leg muscles during a maximal isokinetic task in healthy young adults. A double-blind, randomized, sham-controlled crossover study design was applied. Twenty-seven active young adults completed four sessions, each spaced by 5–8 days. During session 1, dominance was verified with isokinetic strength testing, and subjects were familiarized with the fatigue task (FT). The FT protocol included 40 continuous maximum isokinetic contractions of the knee extensors and flexors (120°/s, concentric/concentric). During Sessions 2–4, tDCS was applied for 20 min with one of three randomly assigned intensities (sham, 2 mA or 4 mA) and the FT was repeated. The anode and cathode of the tDCS device were placed over C3 and the contralateral supraorbital area, respectively. A wireless EMG system collected muscle activity during the FT. The 2 mA tDCS condition had significantly less torque (65.9 ± 32.7 Nm) during the FT than both the sham (68.4 ± 33.9 Nm, p < 0.001) and 4 mA conditions (68.4 ± 33.9 Nm, p = 0.001). Furthermore, the 2 mA condition (33.8 ± 11.7%) had significantly less EMG activity during the FT than both the sham (39.7 ± 10.6%, p < 0.001) and 4 mA conditions (40.5 ± 13.4%, p = 0.001). Contrary to previous submaximal isometric fatigue investigations, the 2 mA tDCS condition significantly reduced torque production and EMG activity of the leg extensors during a maximal isokinetic FT compared with the sham and 4 mA conditions. Also, torque production and EMG activity in the 4 mA condition were not significantly different from sham. Thus, the effects of tDCS, and the underlying mechanisms, might not be the same for different tasks and warrants more investigation.

A computational pipeline to find lobule-specific electric field distribution during non-invasive cerebellar stimulation.

Cerebellar Transcranial direct current stimulation (ctDCS) of cerebellar lobules is challenging due to the complexity of the cerebellar structure. Therefore, we present a freely available computational pipeline to determine the subject-specific lobule-specific electric field distribution during ctDCS. The computational pipeline isolates subject-specific cerebellar lobules based on a spatially unbiased atlas template (SUIT) for the cerebellum, and then calculates the lobule-specific electric field distribution during ctDCS. The computational pipeline was tested using Colin27 Average Brain. The 5 cm × 5 cm anode was placed 3 cm lateral to inion, and the same sized cathode was placed on the contralateral supra-orbital area (called Manto montage) and buccinators muscle (called Celnik montage). A published 4x1 HD-ctDCS electrode montage was also implemented for a comparison using analysis of variance. The electric field strength of both the Celnik and the Manto montages affected the lobules Crus II, VIIb, VIII, and IX of the targeted cerebellar hemispheres while Manto montage had a more bilateral effect. The HD-ctDCS montage primarily affected the lobules Crus I, Crus II, VIIb of the targeted cerebellar hemisphere. Our freely available subject-specific computational modeling pipeline can be used to analyze lobulespecific electric field distribution to select an optimal ctDCS electrode montage.

Meta-analysis of RCTs on the effect of vestibulodynia treatment on female sexual function

Vulvodynia and vestibulodynia affect to some 10% of women, tend to be recurrent, and alter sexual function. A large number of treatments have been suggested, although clinical results are controversial. We carried out a systematic review and meta-analysis of randomized clinical trials (RCTs) to assess changes in sexual function with different treatments. Five datafiles were searched without language restriction, for RCTs comparing any clinical intervention as compared to placebo, sham intervention, or no therapy, until October 2018. The authors independently evaluated eligibility based on articles’ titles, abstracts, and full-text articles. A total of 304 unique records were found, and four RCTs provided information about six interventions: (i) Transcranial direct current stimulation (intensity = 2 mA) for 20 minutes, 10 sessions over a two-weeks period, with the anode positioned over the primary motor cortex, and the cathode, over the contralateral supraorbital area; (ii) transcutaneous electrical nerve stimulation twice a week delivered through a vaginal probe, 20 sessions (10 weeks); (iii) 20 units of botulinum toxin A in 0.5 mL injected symmetrically in the muscle bulbospongiosus; (iv) topical lidocaine; (v) oral desimipramine; and (vi) combined topical lidocaine + oral desimipramine. Sexual function assessment was performed with the Female Sexual Function Index (FSFI), the Index of Sexual Satisfaction (ISS), and the Female Sexual Dysfunction (FSD). Random effects meta-analyses with the inverse variance method were used to evaluate the effects of interventions on outcomes. Effects were expressed as mean differences (MD) and their 95% confidence intervals (CI). There were significant increases in FSFI scores (n = 3 interventions; MD = 5.60; 95%CI 0.98 to 10.22; I2 = 57%; p = 0.02); and for the ISS (n = 3 interventions; MD = −5.14; 95%CI −5.14; 95% CI −9.52 to −0.75; I2 = 51%; p = 0.02). There was not significant difference using the FSD (n = 2 interventions; MD = −3. 69: 95%CI = −2.81 to 10.20; I2 = 0%; p = 0.27). Further studies are needed to confirm found trends to identify the appropriate treatment for vestibulodynia.

Cerebellar Lobules Optimal Stimulation (CLOS): A Computational Pipeline to Optimize Cerebellar Lobule-Specific Electric Field Distribution.

ObjectiveCerebellar transcranial direct current stimulation (ctDCS) is challenging due to the complexity of the cerebellar structure which is reflected by the well-known variability in ctDCS effects. Therefore, our objective is to present a freely available computational modeling pipeline for cerebellar lobules’ optimal stimulation (CLOS).MethodsCLOS can optimize lobule-specific electric field distribution following finite element analysis (FEA) using freely available computational modeling pipelines. We modeled published ctDCS montages with 5 cm × 5 cm anode placed 3 cm lateral to inion, and the same sized cathode was placed on the: (1) contralateral supra-orbital area (called Manto montage), and (2) buccinators muscle (called Celnik montage). Also, a published (3) 4×1 HD-ctDCS electrode montage was modeled. We also investigated the effects of the subject-specific head model versus Colin 27 average head model on lobule-specific electric field distribution. Three-way analysis of variance (ANOVA) was used to determine the effects of lobules, montage, and head model on the electric field distribution. The differences in lobule-specific electric field distribution across different freely available computational pipelines were also evaluated using subject-specific head model. We also presented an application of our computational pipeline to optimize a ctDCS electrode montage to deliver peak electric field at the cerebellar lobules VII-IX related to ankle function.ResultsEta-squared effect size after three-way ANOVA for electric field strength was 0.05 for lobule, 0.00 for montage, 0.04 for the head model, 0.01 for lobule∗montage interaction, 0.01 for lobule∗ head model interaction, and 0.00 for montage∗head model interaction. The electric field strength of both the Celnik and the Manto montages affected the lobules Crus I/II, VIIb, VIII, and IX of the targeted cerebellar hemisphere where Manto montage had a spillover to the contralateral cerebellar hemisphere. The 4×1 HD-ctDCS montage primarily affected the lobules Crus I/II of the targeted cerebellar hemisphere. All three published ctDCS montages were found to be not optimal for ankle function (lobules VII-IX), so we presented a novel HD-ctDCS electrode montage.DiscussionOur freely available CLOS pipeline can be leveraged to optimize electromagnetic stimulation to target cerebellar lobules related to different cognitive and motor functions.

Transcranial Direct Current Stimulation for Patients With Pharmacoresistant Epileptic Spasms: A Pilot Study.

Background: Epileptic spasms (ES) is a severe seizure type and lack of adequate methods for controlling of clinical attacks. Previous studies have indicated that cathodal transcranial direct current stimulation (tDCS) reduces seizure frequency for patients with epilepsy. ES are proposed to have a focal cortical origin. We hypothesized that patients with ES exhibit hyperactive network hubs in the parietal lobe, and that cathodal tDCS targeting the bilateral parietal region can reduce seizure frequency in patients with pharmacoresistant ES.Materials and Methods: The present study consisted of three basic phases: (a) a pre-treatment monitoring period for 14 days; (b) a consecutive 14-day treatment period during which patients were treated with 1 or 2 mA cathode tDCS for 40 min once per day; (c) and a follow-up period for at least 28 days. During the first 20 min of treatment, the cathode was placed over the right parietal lobe (P4) with the reference electrode over the contralateral supra-orbital area. In the second 20 min, the cathode was placed over the left parietal lobe (P3), with the reference electrode over the contralateral supra-orbital area. All patients received active tDCS treatment, and some patients underwent more than one treatment block. Patients maintained a seizure diary throughout the study. Antiepileptic drug therapy remained unchanged throughout the study. K-related samples Friedman tests and two-related samples tests were used to analyze data from all patients.Results: Seven patients with pharmacoresistant ES were included, receiving a total of eighteen 14-day blocks of tDCS treatment. We observed a significant difference in seizure frequency at the second month (p = 0.028, unadjusted), as well as a trend toward decreased seizure frequency at the fourth month (p = 0.068, unadjusted) of the first follow-up, relative to baseline. Three of seven patients (42.9%) exhibited sustained seizure reduction, while one (14.3%) experienced a short-term reduction in seizure frequency following cathodal tDCS treatment. Treatment was well tolerated in all patients.Conclusions: Repeated tDCS with the cathode placed over the bilateral parietal region is safe and may be effective for reducing seizure frequency in a subgroup of patients with pharmacoresistant ES.

The Effect of Anodal Transcranial Direct Current Stimulation Over Left and Right Temporal Cortex on the Cardiovascular Response: A Comparative Study.

Background: Stimulation of the right and left anterior insular cortex, increases and decreases the cardiovascular response respectively, thus indicating the brain’s lateralization of the neural control of circulation. Previous experiments have demonstrated that transcranial direct current stimulation (tDCS) modulates the autonomic cardiovascular control when applied over the temporal cortex. Given the importance of neural control for a normal hemodynamic response, and the potential for the use of tDCS in the treatment of cardiovascular diseases, this study investigated whether tDCS was capable of modulating autonomic regulation.Methods: Cardiovascular response was monitored during a post-exercise muscle ischemia (PEMI) test, which is well-documented to increase sympathetic drive. A group of 12 healthy participants performed a PEMI test in a control (Control), sham (Sham) and two different experimental sessions where the anodal electrode was applied over the left temporal cortex and right temporal cortex with the cathodal electrode placed over the contralateral supraorbital area. Stimulation lasted 20 min at 2 mA. The hemodynamic profile was measured during a PEMI test. The cardiovascular parameters were continuously measured with a transthoracic bio-impedance device both during the PEMI test and during tDCS.Results: None of the subjects presented any side effects during or after tDCS stimulation. A consistent cardiovascular response during PEMI test was observed in all conditions. Statistical analysis did not find any significant interaction and any significant main effect of condition on cardiovascular parameters (all ps > 0.316) after tDCS. No statistical differences regarding the hemodynamic responses were found between conditions and time during tDCS stimulation (p > 0.05).Discussion: This is the first study comparing the cardiovascular response after tDCS stimulation of left and right TC both during exercise and at rest. The results of the current study suggest that anodal tDCS of the left and right TC does not affect functional cardiovascular response during exercise PEMI test and during tDCS. In light of the present and previous findings, the effect of tDCS on the cardiovascular response remains inconclusive.

Evidence Transcranial Direct Current Stimulation Can Improve Saccadic Eye Movement Control in Older Adults.

Objectives: Ageing is associated with declines in voluntary eye movement control, which negatively impact the performance of daily activities. Therapies treating saccadic eye movement control deficits are currently lacking. To address the need for an effective therapy to treat age-related deficits in saccadic eye movement control, the current study investigated whether saccadic behaviour in older adults can be improved by anodal transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex using a montage that has been proven to be effective at improving nonoculomotor control functions. Method: The tDCS protocol entailed a 5 cm × 7 cm anodal electrode and an encephalic cathodal reference electrode positioned over the contralateral supraorbital area. In two experiments, healthy older men completed one active (1.5 mA current for 10 min) and one sham stimulation session, with the session order counterbalanced across participants, and eye movement testing following stimulation. In the first experiment, participants rested during the tDCS (offline), whereas in the follow-up experiment, participants engaged in antisaccades during the tDCS (online). Results: Analyses revealed improvements in saccadic performance following active anodal tDCS relative to sham stimulation in the online experiment, but not in the offline experiment, which was presumably due to the activation of the relevant networks during tDCS promoting more targeted effects. Discussion: These outcomes converge with findings pertaining to nonoculomotor cognitive functions, and provide evidence that tDCS can improve saccadic eye movement control in older adults.

Neurocognitive mechanisms behind emotional attention: Inverse effects of anodal tDCS over the left and right DLPFC on gaze disengagement from emotional faces.

Attention to relevant emotional information in the environment is an important process related to vulnerability and resilience for mood and anxiety disorders. In the present study, the effects of left and right dorsolateral prefrontal cortex (i.e., DLPFC) stimulation on attentional mechanisms of emotional processing were tested and contrasted. A sample of 54 healthy participants received 20 min of active and sham anodal transcranial direct current stimulation (i.e., tDCS) either of the left (n = 27) or of the right DLPFC (n = 27) on two separate days. The anode electrode was placed over the left or the right DLPFC, the cathode over the corresponding contra lateral supraorbital area. After each neurostimulation session, participants completed an eye-tracking task assessing direct processes of attentional engagement towards and attentional disengagement away from emotional faces (happy, disgusted, and sad expressions). Compared to sham, active tDCS over the left DLPFC led to faster gaze disengagement, whereas active tDCS over the right DLPFC led to slower gaze disengagement from emotional faces. Between-group comparisons showed that such inverse change patterns were significantly different and generalized for all types of emotion. Our findings support a lateralized role of left and right DLPFC activity in enhancing/worsening the top-down regulation of emotional attention processing. These results support the rationale of new therapies for affective disorders aimed to increase the activation of the left over the right DLPFC in combination with attentional control training, and identify specific target attention mechanisms to be trained.

Efficacy of transcranial direct current stimulation over primary motor cortex (anode) and contralateral supraorbital area (cathode) on clinical pain severity and mobility performance in persons with knee osteoarthritis: An experimenter- and participant-blinded, randomized, sham-controlled pilot clinical study

BackgroundPrevious studies indicate that transcranial direct current stimulation (tDCS) with anode over motor cortex (M1) and cathode over contralateral supraorbital region (SO) may be effective in reducing pain, but these studies are limited in number and have not focused on older adults with osteoarthritis (OA). ObjectiveTo evaluate the preliminary efficacy and safety of M1-SO applied tDCS on clinical pain severity and mobility performance in adults with knee OA pain. MethodsForty 50- to 70-year-old community-dwelling participants with knee OA were randomly assigned to receive five daily sessions of 2 mA tDCS for 20 min (n = 20) or sham tDCS (n = 20). We measured clinical pain severity via Numeric Rating Scale, Western Ontario and McMaster Universities Osteoarthritis Index, and Short-Form McGill Pain Questionnaire. In addition, we measured mobility performance using the 6-Minute Walk Test and the Short Physical Performance Battery. Moreover, we obtained a sensation/safety questionnaire and measured cognition changes using the PROMIS-Applied Cognition-Abilities-Short Form 8a. ResultsActive tDCS over M1-SO significantly reduced Numeric Rating Scale of pain compared to sham tDCS after completion of the five daily sessions, and remained up to three weeks. No other measures were significantly different from sham. Participants tolerated tDCS over M1-SO well without serious adverse effects or cognition changes. ConclusionAlthough not consistent in all pain measurements, our findings demonstrate promising clinical efficacy for reduction in pain perception for older adults with knee OA. Trial registrationClinicalTrials.gov Identifier NCT02512393.

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

Provoked vestibulodynia is a highly prevalent condition characterized by acute recurrent pain located at the vaginal entrance in response to pressure application or attempted vaginal penetration. Despite a wide variety of treatments offered to women with provoked vestibulodynia, a high proportion of women are refractory to conventional treatment. Transcranial direct-current stimulation is a noninvasive brain stimulation technique that has been shown effective for improving various chronic pain conditions. Growing evidence suggests that the central nervous system could play a key role in provoked vestibulodynia. Targeting the central nervous system could therefore be a promising treatment for women with provoked vestibulodynia. The purpose of this study was to evaluate and compare the efficacy of active and sham transcranial direct-current stimulation in reducing pain intensity during intercourse in patients with provoked vestibulodynia. We conducted a triple-blind, parallel-group, randomized controlled trial. Women aged 17-45 years diagnosed with provoked vestibulodynia by a gynecologist using a validated protocol were randomized to 10sessions of either active transcranial direct-current stimulation (intensity= 2 mA) or 10 sessions of sham transcranial direct-current stimulation, over a 2-week period. Both active and sham transcranial direct-current stimulation were applied for 20 minutes, with the anode positioned over the primary motor cortex, and the cathode over the contralateral supraorbital area. Outcome measures were collected at baseline, 2 weeks after treatment, and at 3-month follow-up by an evaluator blinded to group assignment. The primary objective was to assess pain intensity during intercourse, using a numerical rating scale. Secondary outcomes focused on sexual function and distress, vestibular sensitivity, psychological distress, treatment satisfaction, and patient impression of change. Statistical analyses were conducted on the intention-to-treat basis, and treatment effects were evaluated using a mixed linear model for repeated measures. A total of 40 patients were randomly assigned to receive either active (n= 20) or sham (n= 20) transcranial direct-current stimulation treatments from November 2014 through February 2016. Baseline characteristics were similar between the active and sham transcranial direct-current stimulation groups. In full compliance with the study protocol, every participant followed all courses of the study treatment, including assessments at 2-week and 3-month follow-up. Pain during sexual intercourse was not significantly different between active and sham treatment groups 2 weeks after treatment (P= .84) and at follow-up (P= .09). Mean baseline and 2-week assessment pain intensity were, respectively, 6.8 (95% confidence interval, 5.9-7.7) and 5.6 (95% confidence interval, 4.7-6.5) for active transcranial direct-current stimulation (P= .03) vs 7.5 (95% confidence interval, 6.6-8.4) and 5.7 (95% confidence interval, 4.8-6.6) for sham transcranial direct-current stimulation (P= .001). Nonsignificant differences between the 2 groups were also found in their sexual function and distress after treatment (P > .20) and at follow-up (P > .10). Overall, at 2-week assessment 68% assigned to active transcranial direct-current stimulation reported being very much, much, or slightly improved compared to 65% assigned to sham transcranial direct-current stimulation (P= .82), and still comparable at follow-up: 42% vs 65%, respectively (P= .15). Findings suggest that active transcranial direct-current stimulation is not more effective than sham transcranial direct-current stimulation for reducing pain in women with provoked vestibulodynia. Likewise, no significant effects were found on sexual function, vestibular sensitivity, or psychological distress.

P118 The effect of age and cognitive load on prefrontal neurofunctional lateralization: A tDCS study

Question Neuroimaging studies suggest that brain aging can be characterized by a reduction of hemispheric lateralization while performing tasks that require the use of complex cognitive functions. Recently, some authors proposed that even young people show bilateral neural activation as task demand increased. In most studies, however, task’s difficulty had been parametrically increased in a static and pre-specified way, while individual response to task-demand was not systematically controlled. In the present study we investigate changes in neurofunctional lateralization due to increasing subjective cognitive load in young and older participants performing tasks involving different cognitive functions. Methods 24 young participants and 12 older adults performed a digit span backward (complex cognitive function) and a finger tapping task (basic motor function) at 3 levels of subjective task difficulty (“easy” 5/5 correct answers, “medium” 3/5, “difficult” 1/5) which were established before starting the experiment. Participants took part at three sessions in three different days: two real stimulation conditions and a sham condition. In the real conditions anodal tDCS (20 min, 1.5 mA) was delivered through a target electrode (5 × 5 cm) positioned to stimulate both the inferior frontal gyrus and the primary motor area, once over the left hemisphere and once over the right one. The cathode was placed over the contralateral supraorbital area. Results A 3 (left, right, sham) × 3 (easy, medium, difficult) mixed-model with random intercepts for subjects was run within each group. For the young group a significant interaction between difficulty and stimulation was found: right tDCS deteriorates the performance only during the hardest condition. The preliminary results obtained from the 12 elderlies suggest instead that tDCS influence performance only for the “easy” and “medium” conditions. Conclusions The results support the hypothesis that hemispheric lateralization is influenced by the subjective level of difficulty of the task. Our findings are also consistent with the hypothesis of a limited reserve of cognitive resources. Results will be presented and discussed in relation to recent neurocognitive models of aging.

EP 135. Boosting cognitive control with transcranial alternating current stimulation

Introduction Response inhibition, as a hallmark of executive control, refers to the suppression of actions that are no longer required or that are inappropriate, which supports flexible and goal-directed behaviour in ever-changing environments. In this study, we intend to prove whether the boosting of theta activity by electrical stimulation in the prefrontal cortex (pre-SMA & IFC) would (1) increase theta power in prefrontal cortex; reduce alpha power in OPC; (2) reduce number of errors in a continuous performance task; (3) to see whether pre-SMA or IFG is the important structure for motor response inhibition and process monitoring. Methods The studies were approved by the Ethic Committee of the Faculty of Medicine Christian-Albrechts University Kiel. Stimulation Transcranial alternating current stimulation (tACS) was delivering by a battery driven stimulator (NeuroConn GmbH, Ilmenau, Germany) through conductive-rubber electrodes (9 cm 2 ). So far, 12 subjects participated in four different experimental studies and they received on separate days tACS at three frequencies (6 Hz over preSMA and over rIFG, 20 Hz (frequency of no interest) over rIFG and sham stimulation. The minimum period between sessions for a single subject was 7 days. To stimulate pre-SMA: 4 cm anterior to Cz ( matches Fz) and reference electrode over contralateral supraorbital area ; to stimulate IFG: crossing point between T8-Fz and AF8-Cz. Go/NoGo task each stimulus was displayed for 0.2 s and the inter-trial interval was 1.5 s. Participants were asked to respond to all digits except of “5” by pressing a button with the right index finger. Digits “1–4” and “6-9” are thus the Go stimuli and digit “5” the NoGo stimulus. Correct Go-trials were categorized as “hits”, correct No-Go-trials as “withholds”, and responses on No-Go as “false alarms”. Results Preliminary results with 14 subjects in each condition indicate that there’s a significant difference in reaction times between hits and false alarms (in all conditions), which is consistent with the literature. Regarding the differences between conditions, there are no significant statistical differences as of now, but this might be due to the small number of subjects in each condition. There seem to be slight trends for 6Hz pSMA compared to sham: Mean reaction times for hits and false alarms were highest for 6 Hz stimulation at the pSMA. Regarding the ratio of hits and false alarms (actual number divided by potential number), subjects had the highest ratio of hits in sham stimulation and the lowest ratio in 6 Hz stimulation of pSMA. The pattern for false alarms is similar: subjects had the lowest ratio of FAs in 6 Hz stimulation of pSMA with all other conditions appearing mostly equal. Conclusion Our behavioral results so far showed that tACS could have potential in modulating behavioral responses, however future studies could improve on this study by analyzing EEG-data as correlates of the behavioral data and having larger sample sizes.

Optimizing Rehabilitation for Phantom Limb Pain Using Mirror Therapy and Transcranial Direct Current Stimulation: A Randomized, Double-Blind Clinical Trial Study Protocol.

BackgroundDespite the multiple available pharmacological and behavioral therapies for the management of chronic phantom limb pain (PLP) in lower limb amputees, treatment for this condition is still a major challenge and the results are mixed. Given that PLP is associated with maladaptive brain plasticity, interventions that promote cortical reorganization such as non-invasive brain stimulation and behavioral methods including transcranial direct current stimulation (tDCS) and mirror therapy (MT), respectively, may prove to be beneficial to control pain in PLP. Due to its complementary effects, a combination of tDCS and MT may result in synergistic effects in PLP.ObjectiveThe objective of this study is to evaluate the efficacy of tDCS and MT as a rehabilitative tool for the management of PLP in unilateral lower limb amputees.MethodsA prospective, randomized, placebo-controlled, double-blind, factorial, superiority clinical trial will be carried out. Participants will be eligible if they meet the following inclusion criteria: lower limb unilateral traumatic amputees that present PLP for at least 3 months after the amputated limb has completely healed. Participants (N=132) will be randomly allocated to the following groups: (1) active tDCS and active MT, (2) sham tDCS and active MT, (3) active tDCS and sham MT, and (4) sham tDCS and sham MT. tDCS will be applied with the anodal electrode placed over the primary motor cortex (M1) contralateral to the amputation side and the cathode over the contralateral supraorbital area. Stimulation will be applied at the same time of the MT protocol with the parameters 2 mA for 20 minutes. Pain outcome assessments will be performed at baseline, before and after each intervention session, at the end of MT, and in 2 follow-up visits. In order to assess cortical reorganization and correlate with clinical outcomes, participants will undergo functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) before and after the intervention.ResultsThis clinical trial received institutional review board (IRB) approval in July of 2015 and enrollment started in December of 2015. To date 2 participants have been enrolled. The estimate enrollment rate is about 30 to 35 patients per year; thus we expect to complete enrollment in 4 years.ConclusionsThis factorial design will provide relevant data to evaluate whether tDCS combined with MT is more effective than each therapy alone, as well as with no intervention (sham/sham) in patients with chronic PLP after unilateral lower limb amputation. In addition, this randomized clinical trial will help to investigate the neurophysiological mechanisms underlying the disease, which could potentially provide relevant findings for further management of this chronic condition and also help to optimize the use of this novel intervention.Trial RegistrationClinicaltrials.gov NCT02487966; https://clinicaltrials.gov/ct2/show/NCT02487966 (Archived by WebCite at http://www.webcitation.org/6i3GrKMyf)

Modulation of large-scale brain networks by transcranial direct current stimulation evidenced by resting-state functional MRI

Brain areas interact mutually to perform particular complex brain functions such as memory or language. Furthermore, under resting-state conditions several spatial patterns have been identified that resemble functional systems involved in cognitive functions. Among these, the default-mode network (DMN), which is consistently deactivated during task periods and is related to a variety of cognitive functions, has attracted most attention. In addition, in resting-state conditions some brain areas engaged in focused attention (such as the anticorrelated network, AN) show a strong negative correlation with DMN; as task demand increases, AN activity rises, and DMN activity falls. We combined transcranial direct current stimulation (tDCS) with functional magnetic resonance imaging (fMRI) to investigate these brain network dynamics. Ten healthy young volunteers underwent four blocks of resting-state fMRI (10-minutes), each of them immediately after 20 minutes of sham or active tDCS (2 mA), on two different days. On the first day the anodal electrode was placed over the left dorsolateral prefrontal cortex (DLPFC) (part of the AN) with the cathode over the contralateral supraorbital area, and on the second day, the electrode arrangement was reversed (anode right-DLPFC, cathode left-supraorbital). After active stimulation, functional network connectivity revealed increased synchrony within the AN components and reduced synchrony in the DMN components. Our study reveals a reconfiguration of intrinsic brain activity networks after active tDCS. These effects may help to explain earlier reports of improvements in cognitive functions after anodal-tDCS, where increasing cortical excitability may have facilitated reconfiguration of functional brain networks to address upcoming cognitive demands.