Determining the Effect of Transcranial Direct Current Stimulation on Depression and Anxiety in Methadone Consumers: A Randomized Controlled: Erratum

BackgroundPatients with Alzheimer’s disease frequently elicit neuropsychiatric symptoms as well as cognitive deficits. Above all, depression is one of the most common neuropsychiatric symptoms in Alzheimer’s disease but antidepressant drugs have not shown significant beneficial effects on it. Moreover, electroconvulsive therapy has not ensured its safety for potential severe adverse events although it does show beneficial clinical effect. Transcranial direct current stimulation can be the safe alternative of neuromodulation, which applies weak direct electrical current to the brain. Although transcranial direct current stimulation has plausible evidence for its effect on depression in young adult patients, no study has explored it in older subjects with depression in Alzheimer’s disease. Therefore, we present a study protocol designed to evaluate the safety and clinical effect of transcranial direct current stimulation on depression in Alzheimer’s disease in subjects aged over 65 years.MethodThis is a two-arm, parallel-design, randomized controlled trial, in which patients and assessors will be blinded. Subjects will be randomized to either an active or a sham transcranial direct current stimulation group. Participants in both groups will be evaluated at baseline, immediately, and 2 weeks after the intervention.DiscussionThis study investigates the safety and effect of transcranial direct current stimulation that may bring a significant impact on both depression and cognition in patients with Alzheimer’s disease, and may be useful to enhance their quality of life.Trial registrationClinicalTrials.gov, NCT02351388. Registered on 27 January 2015. Last updated on 30 May 2016.

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.

INTRODUCTION: Temporomandibular disorder (TMD) is currently considered a central sensitization syndrome that belongs to the orofacial nociplastic pain group and offers great challenges for clinical practice. It can also be identified in individuals with sickle cell disease. Neuromodulation is a promising therapy that can help individuals with refractory chronic pain. To our knowledge, there is no treatment proposal for these individuals with chronic orofacial pain resulting from sickle cell disease. OBJECTIVE: This is a protocol of a randomized, double-blind, cross-over clinical trial. The purpose of this protocol is to investigate whether the immediate effect of transcranial direct current stimulation can be increased by adding the effect of peripheral sensory electrical stimulation. METHODS: Twenty women between 18 and 49 years of age will be screened to participate in this cross-over study where they will all receive the three types of protocol with a one-week washout. Active transcranial Direct Current Stimulation (tDCS) + active Peripheral Electrical Stimulation (PES); Active tDCS + PES sham and tDCS sham + PES sham. Stimulation with tDCS will be at 2 mA anodic over the motor cortex for 20 minutes ipsilateral to the most painful temporomandibular joint (TMJ). Peripheral electrical stimulation will be at 100 Hz over the most painful TMJ masseter muscle for 30 min. OUTCOME: The main outcome will be pain intensity assessed by VAS scale and by a pressure algometer in grams. In addition, endogenous pain modulation will be analyzed through the temporal summation of pain with Aesthesio precision tactile sensory filaments and conditioned pain modulation (CPM) evaluated by an algometer and thermal conditioned stimulus, as secondary outcomes. Data will be analyzed using ANOVA of repeated measures, controlling for confounding variables.

Objective To investigate the effect of high-definition transcranial direct current stimulation on visual spatial working memory in patients with schizophrenia. Methods Sixty-six patients with schizophrenia were enrolled in a randomized, double-blind, placebo-controlled study. The subjects were randomized into a true stimulation group of 33 patients and a placebo control group of 33 patients, each patient only received one stimulation. After receiving a stimulus, the left dorsolateral prefrontal lobe was stimulated by high-precision transcranial direct current. The true stimulation group was stimulated with a current of 1.5 mA for 20 min. The control group used pseudo-stimulation, and only the current was passed within 30 s of the beginning and the end of the stimulation. Both groups completed the neuropsychological background test and the n-back task before stimulation, and the stimulation was performed after five days. After the stimulation, the two groups completed the n-back task again, and compared the Changes in grades to reflect changes in working memory before and after the pseudo-stimulation. Results Before the stimulation, the response rate of the 3-back task was compared with that of the control group ((0.32±0.21), (0.32±0.22)), the true stimulation group ((0.28±0.19), (0.35±0.21)), and the difference was statistically significant (F=5.298, P=0.025). Conclusion Using high-definition transcranial direct current stimulation to stimulate the left dorsolateral prefrontal cortex using can improve the visual memory function of patients. In the future, this technique can be applied to the cognitive promotion of memory impairment in patients with schizophrenia. Key words: Transcranial direct current stimulation; Working memory; Schizophrenia

There is a growing body of literature suggesting transcranial direct current stimulation (tDCS) is effective in accelerating certain types of memory including working memory, language learning, and object recognition. Recent studies have provided new evidence that non-declarative memories such as motor skill acquisition may be enhanced through direct stimulation of motor cortex. Additionally, Galea and Celnik (J Neurophysiol 102:294–301, [10]) showed that inhibition of the prefrontal cortex following motor training led to enhanced procedural memory consolidation. This effort examined the effects of excitatory transcranial direct current stimulation (tDCS) over the primary motor cortex on memory acquisition and inhibitory tDCS over dorsolateral prefrontal cortex in memory consolidation. Thirty-six Air Force members volunteered to participate. They were divided into four groups: anodal tDCS over motor cortex, cathodal stimulation over dorsolateral prefrontal cortex (DLPFC), both anodal tDCS over motor cortex and cathodal tDCS over DLPFC, or sham tDCS over motor cortex and DLFPC. All participants received their stimulation condition while training on a procedural task that required them to identify incoming aircraft as friend or foe. Twenty-four hours after the training session, participants returned to the lab for retention testing. When comparing the day 1 (training) scores to the day 2 (test) score, the results showed the cathodal tDCS group performed 2× better than sham and all real tDCS groups exhibited scores significantly higher than sham. The evidence suggests that inhibition of the prefrontal cortex leads to the greatest improvement in performance. We hypothesize that this is a result of a shift in dominance of the declarative memory system to the non-declarative procedural system, which improves consolidation of the procedural memories gained during training.

This study aimed at the effects of anodal transcranial direct current stimulation (tDCS) over the right posterior parietal cortex on the control of visual attention during walking in healthy adults. Twenty-four healthy participants received two conditions of tDCS (anodal and sham) in a double-blind, cross-over, and sham-controlled experimental study. The stimulus-response compatibility (SRC) effects were measured for assessing the control of visual attention at pre-intervention periods, immediate post-intervention periods, and 30 min after the intervention. Two-way repeated-measure analysis of variance was used to analyze the effects of time and stimulation condition in the entire field of view and each field of view (left and right). No significant changes in the SRC effects were observed in the entire field of view with respect to time (P = 0.14), tDCS condition (P = 0.42), and the combination of time and stimulation conditions (P = 0.66). Likewise, no significant changes in the SRC effects were observed in the left and right fields of view with respect to time (P = 0.08 and P = 0.78, respectively), tDCS condition (P = 0.17 and P = 0.98, respectively), and the combination of time and stimulation conditions (P = 0.37 and P = 0.85). Future studies using different stimulus conditions of tDCS (e.g., different electrode montage or timing of application) are required to evaluate the effects of tDCS on the control of visual attention during walking.

Introduction: Pain following spinal cord injury (SCI) is notoriously difficult to manage and often refractory to treatment. Novel approaches, such as non-invasive brain stimulation, targeting central mechanisms associated with chronic pain, have shown early promise as a safe treatment in various patient groups, including spinal cord injury. To date the number of small clinical trials using non-invasive brain stimulation to treat chronic pain in SCI has produced mixed results. We report here the findings of a UK based trial examining the effects of anodal transcranial direct current stimulation (TdCs) administration on pain in spinal injury patients. Methods: Sixteen spinal injury patients from the National Spinal Injury Centre, Stoke Mandeville Hospital, Aylesbury, UK participated in a single centre, double blind randomized control trial. Patients were randomly allocated to either the active (n=8) or sham (n=8) treatment groups. tDCS was administered by electrodes with anode placement over the dominant M1 and the cathode electrode over the contralateral supraorbit scalp area. Subjects received either active (2 mA anodal current) or sham tDCS for 20 min daily treatment for 5 consecutive days with the dose based on previously reported chronic pain studies in spinal cord injury patients. A mixed ANOVA was used to evaluate both tDCS treatment and time effects on validated assessment measures for pain and depression up to 2 weeks following treatment intervention. Results: No adverse effects of the treatment were observed in this study, nor were there any significant differences between groups in rating perception of stimulation. While treatment appeared to have reduced group pain scores on a visual analogue scale [VAS], there were no statistically significant differences between active and sham treatment groups when re-examined in the 2 week follow up. Conclusion: There were some reductions in self-assessed VAS pain score in our small group of SCI patients during treatment in both the sham and active tDCS and at two weeks’ post treatment. However, our study appears to indicate only a placebo-like effect of tDCS on chronic pain in SCI, and not one attributed to the active, anodal stimulation over motor cortex. We also did not observe any significant effects over time or treatment for an assessment of neuropathic pain. We observed some trends of non-significant reduction in some of selfassessed pain scores measures, however, these are inconclusive. Studies of clinical efficacy of pain treatment by tDCS in spinal cord injury should therefore be conducted on a larger scale, and with a longer follow up period to address the limited evidence available.

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.

Aims: To test the effect of repetitive active transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) associated with a hypocaloric diet (HD) on glucose homeostasis in overweight or obese adults. Method: We selected in a RCT double-blind study, overweight or obese adults with different degrees of glucose tolerance to complete a 4-week (20 sessions; five consecutive weekdays) of fixed-dose tDCS (2mA, 20min) delivered over the right DLPFC associated with a standard HD. Subjects were randomly assigned (1:1) and stratified by sex to active tDCS group (AG) or sham tDCS group (SG). Changes on the glycemic and insulinemic response were assessed in a 4h liquid meal tolerance test (LMTT), performed before (t0) and after (t20) the 4-week intervention. Plasma glucose and insulin concentrations were used to determine glucose and insulin AUCs, indices of insulin sensitivity (MISI, Matsuda Insulin Sensitivity Index), insulin secretion (ISI, Insulin Secretion Index), and pancreatic β-cell function (DI, Disposition Index). Data were analyzed with generalized estimating equations adjusted for age, carbohydrate intake, and weight loss (%). Results: Twenty-eight participants were randomized (79% obese; 29% IGT, 4% T2D; 37.6 [5.8] years). Changes over the time (mean [95% CI]) for FPG was higher in AG than in SG (∆t20-t0 = −7.8 [−14.0, −1.6] vs. ∆t20-t0 = −0.9 [−4.0, 2.1] mg/dL; p = 0.043) after the intervention. Likewise, the MISI was improved in AG compared with SG (∆t20-t0 = 3.2 [1.5 to 4.9] vs. ∆t20-t0 = 0.5 [−1.5, 2.5] pmol-1x mmol-1; p = 0.044). There were no significant differences between groups in fasting insulin, glucose and insulin AUCs, ISI, or DI over the study. Conclusions: Repetitive active tDCS over the right DLPFC may be a promising non-invasive technique that could be used to improve glucose homeostasis in overweight or obese individuals on a low-calorie diet. ClinicalTrials.org: NCT02683902. Disclosure C. de Araujo: None. R.C. Fitz: None. G.R. Natividade: None. A.F. Osório: None. P.N. Merello: None. P. Schestatsky: None. F. Gerchman: Speaker's Bureau; Self; Novo Nordisk Inc. Other Relationship; Self; Sanofi-Aventis. Funding Hospital de Clínicas de Porto Alegre (FIPE15-0119, 16-0417)

Effect of direct current stimulation on bone growth after distraction epiphysiolysis of the rabbit tibia

Transcranial direct current stimulation (tDCS) is an emerging, noninvasive technique of neurostimulation for treating pain. However, the mechanisms and pathways involved in its analgesic effects are poorly understood. Therefore, we investigated the effects of direct current stimulation (DCS) on thermal and mechanical nociceptive thresholds and on the activation of the midbrain periaqueductal gray (PAG) and the dorsal horn of the spinal cord (DHSC) in rats; these central nervous system areas are associated with pain processing. Male Wistar rats underwent cathodal DCS of the motor cortex and, while still under stimulation, were evaluated using tail-flick and paw pressure nociceptive tests. Sham stimulation and naive rats were used as controls. We used a randomized design; the assays were not blinded to the experimenter. Immunoreactivity of the early growth response gene 1 (Egr-1), which is a marker of neuronal activation, was evaluated in the PAG and DHSC, and enkephalin immunoreactivity was evaluated in the DHSC. DCS did not change the thermal nociceptive threshold; however, it increased the mechanical nociceptive threshold of both hind paws compared with that of controls, characterizing a topographical effect. DCS decreased the Egr-1 labeling in the PAG and DHSC as well as the immunoreactivity of spinal enkephalin. Altogether, the data suggest that DCS disinhibits the midbrain descending analgesic pathway, consequently inhibiting spinal nociceptive neurons and causing an increase in the nociceptive threshold. This study reinforces the idea that the motor cortex participates in the neurocircuitry that is involved in analgesia and further clarifies the mechanisms of action of tDCS in pain treatment.

Perceiving human motion, recognizing actions, and interpreting emotional body language are tasks we perform daily and which are supported by a network of brain areas including the human posterior superior temporal sulcus (pSTS). Here, we applied transcranial direct current stimulation (tDCS) with anodal (excitatory) or cathodal (inhibitory) electrodes mounted over right pSTS (target) and orbito-frontal cortex (reference) while healthy participants performed a bodily emotion recognition task using biological motion point-light displays (PLDs). Performance (accuracy and reaction times) was also assessed on a control task which was matched to the emotion recognition task in terms of cognitive and motor demands. Each subject participated in two experimental sessions, receiving either anodal or cathodal stimulation, which were separated by one week to avoid residual effects of previous stimulations. Overall, tDCS brain stimulation did not affect the recognition of emotional states from PLDs. However, when emotions with a negative or positive–neutral emotional valence were analyzed separately, effects of stimulation were shown for recognizing emotions with a negative emotional valence (sadness and anger), indicating increased recognition performance when receiving anodal (excitatory) stimulation compared to cathodal (inhibitory) stimulation over pSTS. No stimulation effects were shown for the recognition of emotions with positive–neutral emotional valences. These findings extend previous studies showing structure–function relationships between STS and biological motion processing from PLDs and provide indications that stimulation effects may be modulated by the emotional valence of the stimuli.

ABSTRACTMultitasking is the ability to perform more than one task simultaneously. The need to multitask is common in many industries especially within the military with tasks such as air traffic controllers, cyber defense operators and image analysts. However, as the time on task increases, information throughput can become overwhelming resulting in a performance decrement. Through task prioritizing, the operator is able to maintain performance on specific subtasks in which they selected as high importance while other subtasks experience a decrement. The objective of this study was to evaluate the effects of transcranial direct current stimulation (tDCS) applied to the left dorsolateral prefrontal cortex (ldLPFC) on information processing capabilities to improve individual and overall multitasking performance while performing the multi-attribute task battery (MATB). Two groups of 8 participants each received either 2 mA of anodal or sham tDCS while performing MATB. In addition, eye tracking was implemented to record eye movement patterns. In doing so, we were able to determine how much time the operator allocated to each of the subtasks within MATB and how their task priorities changed as workload demands increased. The findings provided evidence that 2 mA of anodal tDCS during MATB significantly improved overall information throughput compared to the sham group. With respect to the individual subtasks, communication and system monitoring displayed the greatest enhancement with anodal tDCS. Our data suggests that tDCS could be a useful tool to enhance information processing capabilities during a multitasking paradigm resulting in improved processing capabilities and information throughput.

Background: Beneficial effects of transcranial direct current stimulation (tDCS) are relevant to cognition and functional capacity, in addition to psychiatric symptoms in patients with schizophrenia. However, whether tDCS would improve higher-order cognition, e.g., semantic memory organization, has remained unclear. Recently, text-mining analyses have been shown to reveal semantic memory. The purpose of the current study was to determine whether tDCS would improve semantic memory, as evaluated by text-mining analyses of category fluency data, in patients with schizophrenia.Methods: Twenty-eight patients entered the study. Cognitive assessment including the category fluency task was conducted at baseline (before tDCS treatment) and 1 month after t administration of tDCS (2 mA × 20 min, twice per day) for 5 days, according to our previous study. The category fluency data were also obtained from 335 healthy control subjects. The verbal outputs (i.e., animal names) from the category fluency task were submitted to singular valued decomposition (SVD) analysis. Semantic memory structures were estimated by calculating inter-item cosines (i.e., similarities) among animal names frequently produced in the category fluency task. Data were analyzed longitudinally and cross-sectionally to compare the semantic structure within the patient group (i.e., baseline vs. follow-up) and between groups (patients vs. healthy controls). In the former, semantic associations for frequent items were compared in the form of cosine profiles, while in the latter, the difference in the magnitude of the correlations for inter-item cosines between healthy controls and patients (baseline, follow-up) was examined.Results: Cosine profiles in the patient group became more cluster-based (i.e., pet, carnivores, and herbivores) at follow-up compared to those at baseline, yielding higher cosines within subcategories. The correlational coefficient of inter-item cosines between healthy controls and patients was significantly greater at follow-up compared to baseline; semantic associations in patients approached the normality status after multi-session tDCS.Conclusions: To our knowledge, this is the first study to demonstrate the facilitative effect of tDCS on semantic memory organization in patients with schizophrenia. Text-mining analysis was indicated to effectively evaluate semantic memory structures in patients with psychiatric disorders.

Motor recovery is related to the corticospinal tract (CST) lesion in post-stroke patients. The CST originating from the supplementary motor area (SMA) affects the recovery of impaired motor function. We confirmed the effects of transcranial direct current stimulation (tDCS) over the SMA combined with walk training on CST excitability. This study involved a stroke patient with severe sensorimotor deficits and a retrospective AB design. Walk training was conducted only in phase A. Phase B consisted of anodal tDCS (1.5 mA) combined with walk training. Walking speed, stride time variability (STV; reflecting gait stability), and beta-band intramuscular coherence—derived from the paired tibialis anterior on the paretic side (reflecting CST excitability)—were measured. STV quantified the coefficient of variation in stride time using accelerometers. Intramuscular coherence during the early stance phase noticeably increased in phase B compared with phase A. Intramuscular coherence in both the stance and swing phases was reduced at follow-up. Walking speed showed no change, while STV was noticeably decreased in phase B compared with phase A. These results suggest that tDCS over the SMA during walking improves gait stability by enhancing CST excitability in the early stance phase.