Anodal transcranial direct-current stimulation and non-verbal intelligence in autism spectrum disorder: A randomized controlled trial.

AIM: To understand the impact of anodal transcranial direct-current stimulation (tDCS) on non-verbal intelligence in high-functioning young adults with autism spectrum disorder (ASD). METHOD: Thirty individuals with ASD were randomly divided into three groups receiving 2 mA, 20 minutes daily anodal tDCS for 10 sessions. Group A received 10 sham tDCS sessions, group B five real followed by five sham sessions, and group C received 10 real tDCS sessions. The total score of non-verbal intelligence was measured using the Test of Nonverbal Intelligence, Fourth Edition. The left dorsolateral prefrontal cortex (LDLPFC) was targeted using the International 10-20 electroencephalography system, and concurrent cognitive training was avoided. RESULTS: Group C demonstrated a mean difference of 4.10 (95% confidence interval 1.41-6.79; p = 0.005) in Test of Nonverbal Intelligence scores compared with group A, with an effect size of 0.47. No significant differences were observed between groups A and B (p = 0.296), or between groups B and C (p = 0.140). INTERPRETATION: Ten sessions of anodal tDCS to the LDLPFC led to improved non-verbal intelligence among individuals with ASD. These results emphasize the potential of tDCS as a discrete method for boosting cognitive abilities in the high-functioning population with ASD. Future studies with larger groups of participants and extended observation periods are necessary to validate these findings.

Long-term effects of transcranial direct current stimulation in the treatment of autism spectrum disorder: A randomized controlled trial.

AIM: To compare the efficacy of 0, 5, and 20 sessions of transcranial direct current stimulation (tDCS) for reducing symptoms of autism spectrum disorder (ASD). METHOD: Thirty-six male children with ASD (mean age 2 years 3 months, SD 4 months, age range 1 years 6 months-2 years 11 months) were balanced and stratified by age, sex, and baseline severity of ASD, to: (1) a control group that received 20 sessions of sham tDCS; (2) a 5-session tDCS group (5-tDCS) that received 5 sessions of active tDCS followed by 15 sessions of sham tDCS; and (3) a 20-session tDCS group (20-tDCS) that received 20 sessions of active tDCS. All groups participated in the special school activity of Khon Kaen Special Education Center, Thailand. The primary outcome was autism severity as measured by the Childhood Autism Severity Scale. RESULTS: The 5-tDCS and 20-tDCS groups evidenced greater reductions in autism severity than the control group at days 5 and 14, and months 6 and 12. There were no significant differences in the outcome between the 5- and 20-tDCS groups at any time point. Within-group analysis showed clinically meaningful improvements starting at month 6 for the participants in the control group, and clinically meaningful improvements starting on day 5 in both active tDCS groups, all of which were maintained to month 12. INTERPRETATION: The 5- and 20-session tDCS seems to reduce autism severity faster than sham tDCS. These effects maintained at least for 1 year. WHAT THIS PAPER ADDS: Twenty sessions of transcranial direct current stimulation (tDCS) were not superior to five sessions. Sham tDCS with a special school activity can reduce autism severity starting at 6 months after treatment. The benefits observed for 5 and 20 sessions of tDCS last for at least 12 months.

Brain Metabolite Changes After Anodal Transcranial Direct Current Stimulation in Autism Spectrum Disorder.

OBJECTIVES: Previous research has provided evidence that transcranial direct current stimulation (tDCS) can reduce severity of autism spectrum disorder (ASD); however, the exact mechanism of this effect is still unknown. Magnetic resonance spectroscopy has demonstrated low levels of brain metabolites in the anterior cingulate cortex (ACC), amygdala, and left dorsolateral prefrontal cortex (DLPFC) in individuals with ASD. The aim of this study was to investigate the effects of anodal tDCS on social functioning of individuals with ASD, as measured by the social subscale of the Autism Treatment Evaluation Checklist (ATEC), through correlations between pretreatment and posttreatment concentrations of brain metabolites in the areas of interest (DLPFC, ACC, amygdala, and locus coeruleus) and scores on the ATEC social subscale. METHODS: Ten participants with ASD were administered 1 mA anodal tDCS to the left DLPFC for 20 min over five consecutive days. Measures of the ATEC social subscale and the concentrations of brain metabolites were performed before and immediately after the treatment. RESULTS: The results showed a significant decrease between pretreatment and immediately posttreatment in the ATEC social subscale scores, significant increases in N-acetylaspartate (NAA)/creatine (Cr) and myoinositol (mI)/Cr concentrations, and a decrease in choline (Cho)/Cr concentrations in the left DLPFC and locus coeruleus after tDCS treatment. Significant associations between decreased ATEC social subscale scores and changed concentrations in NAA/Cr, Cho/Cr, and mI/Cr in the locus coeruleus were positive. CONCLUSION: Findings suggest that beneficial effects of tDCS in ASD may be due to changes in neuronal and glia cell activity and synaptogenesis in the brain network of individuals with ASD. Further studies with larger sample sizes and control groups are warranted.

Living and Training at 825 m for 8 Weeks Supplemented With Intermittent Hypoxic Training at 3,000 m Improves Blood Parameters and Running Performance.

Wonnabussapawich, P, Hamlin, MJ, Lizamore, CA, Manimmanakorn, N, Leelayuwat, N, Tunkamnerdthai, O, Thuwakum, W, and Manimmanakorn, A. Living and training at 825 m for 8 weeks supplemented with intermittent hypoxic training at 3,000 m improves blood parameters and running performance. J Strength Cond Res 31(12): 3287-3294, 2017-We aimed to investigate the effect of an 8-week low-altitude training block supplemented with intermittent hypoxic training, on blood and performance parameters in soccer players. Forty university-level male soccer players were separated into altitude (n = 20, 825 m) or sea-level (n = 20, 125 m) groups. Before (1-2 days ago) and after (1 and 14 days later) training, players were asked to give a resting venous blood sample and complete a series of performance tests. Compared with sea level, the altitude group increased erythropoietin, red blood cell (RBC) count, and hematocrit 1 day after training (42.6 ± 24.0%, 1.8 ± 1.3%, 1.4 ± 1.1%, mean ± 95% confidence limits (CL), respectively). By 14 days after training, only RBC count and hemoglobin were substantially higher in the altitude compared with the sea-level group (3.2 ± 1.8%, 2.9 ± 2.1% respectively). Compared with sea level, the altitude group 1-2 days after training improved their 50-m (-2.9 ± 1.4%) and 2,800-m (-2.9 ± 4.4%) run times and demonstrated a higher maximal aerobic speed (4.7 ± 7.4%). These performance changes remained at 14 days after training with the addition of a likely higher estimated V[Combining Dot Above]O2max in the altitude compared with the sea-level group (3.2 ± 3.0%). Eight weeks of low-altitude training, supplemented with regular bouts of intermittent hypoxic training at higher altitude, produced beneficial performance improvements in team-sport athletes, which may increase the viability of such training to coaches and players that cannot access more traditional high altitude venues.

Transient Changes in Brain Metabolites after Transcranial Direct Current Stimulation in Spastic Cerebral Palsy: A Pilot Study.

BACKGROUND: Muscle spasticity is a disability caused by damage to the pyramidal system. Standard treatments for spasticity include muscle stretching, antispastic medications, and tendon release surgeries, but treatment outcomes remain unsatisfactory. Anodal transcranial direct current stimulation (tDCS) in patients with muscle spasticity is known to result in significant improvement in spastic tone (p < 0.001). However, the mechanism of action by which tDCS treatment affects spasticity remains unclear. This pilot study aimed to investigate the effect of anodal tDCS upon brain metabolites in the left basal ganglia and ipsilateral primary motor cortex (M1) in children with spastic cerebral palsy (CP). MATERIALS AND METHODS: This study consisted of three steps: a baseline evaluation, a treatment period, and a follow-up period. During the treatment period, patients were given 20 min of 1 mA anodal tDCS over the left M1 for five consecutive days. Outcomes were compared between pre- and immediate posttreatment in terms of brain metabolites, Tardieu scales, and the quality of upper extremity skills test. RESULTS: Ten patients with spastic CP were enrolled. Following tDCS, there were significant increases in the ratio of N-acetylaspartate (NAA)/creatine (Cr) (p = 0.030), choline (Cho)/Cr (p = 0.043), and myoinositol (mI)/Cr (p = 0.035) in the basal ganglia. Moreover, increased glutamine-glutamate (Glx)/Cr ratio in the left M1 (p = 0.008) was found. In addition, we also observed improvements in the extent of spasticity and hand function (p = 0.028). CONCLUSION: Five consecutive days of anodal tDCS over the left M1 appeared statistically to reduce the degree of spasticity and increase NAA, Cho, mI, and Glx. Future research studies, involving a larger sample size of spastic CP patients undergoing tDCS is now warranted.

Exercise Intensity and Substrate Utilization in Healthy Sedentary Females Using the Life-Build-Line Device.

Background: Life-Build-Line (LBL) is a new exercise device that is convenient, and not so expensive. Together with the style of movement, it may boost one to adhere to the exercise regimen and thereby promote better health. However, no study has proved its exercise intensity and effect on substrate utilization. Objective: To investigate exercise intensity in healthy sedentary women using LBL and measure their substrate utilization during exercise. The former session was determined by measuring absolute [i.e., energy expenditure (EE)] and relative [i.e., percentage of rate of peak oxygen consumption (V̇O2 peak), maximal heart rate (HRmax ), rating of perceived exertion (RPE), and rating of perceived dyspnea (RPD)] indicators, whereas the latter was determined by measuring oxygen consumption and carbon dioxide production (V̇CO2). Material and Method: Ten female subjects randomly performed two visits of exercise at least seven days apart. The first was a peak exercise test, and the second consisted of three 30-minute sessions of rest, exercise with LBL, and recovery. The V̇O2, V̇CO2, and EE were determined based on the expired air at the last five minutes of resting and exercise, whereas electrocardiograms were recorded to measure HR throughout the three sessions. Subjects were asked to provide RPE and RPD at the end of the exercise session. Results: During exercise with LBL, average %V̇O2 peak and %HRmax were 43.5%±2.32% and 52.8%±1.81%, respectively, while EE, RPE, and RPD were 3.01±0.53 metabolic equivalents, 12.2±1.8, and 3.0±1.41, respectively. In addition, fat and especially CHO utilization were increased by the exercise. Conclusion: These findings indicate that LBL offers a means of low-intensity exercise in healthy females while still providing physiological and metabolic benefits

Transcranial Direct Current Stimulation for Treatment of Childhood Pharmacoresistant Lennox-Gastaut Syndrome: A Pilot Study.

BACKGROUND: Lennox-Gastaut syndrome (LGS) is a severe childhood epileptic syndrome with high pharmacoresistance. The treatment outcomes are still unsatisfied. Our previous study of cathodal transcranial direct current stimulation (tDCS) in children with focal epilepsy showed significant reduction in epileptiform discharges. We hypothesized that cathodal tDCS when applied over the primary motor cortex (M1) combined with pharmacologic treatment will be more effective for reducing seizure frequency in patients with LGS than pharmacologic treatment alone. MATERIALS AND METHODS: Study participants were randomized to receive either (1) pharmacologic treatment with five consecutive days of 2 mA cathodal tDCS over M1 for 20 min or (2) pharmacologic treatment plus sham tDCS. Measures of seizure frequency and epileptic discharges were performed before treatment and again immediately post-treatment and 1-, 2-, 3-, and 4-week follow-up. RESULT: Twenty-two patients with LGS were enrolled. Participants assigned to the active tDCS condition reported significantly more pre- to post-treatment reductions in seizure frequency and epileptic discharges that were sustained for 3 weeks after treatment. CONCLUSION: Five consecutive days of cathodal tDCS over M1 combined with pharmacologic treatment appears to reduce seizure frequency and epileptic discharges. Further studies of the potential mechanisms of tDCS in the LGS are warranted. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02731300 (https://register.clinicaltrials.gov).

Improvement of pulmonary function with arm swing exercise in patients with type 2 diabetes.

[Purpose] Obesity and hyperglycemia play roles in the impairment of pulmonary function in type 2 diabetes mellitus (T2DM) patients. Low-intensity exercise is known to reduce body fat and improve hyperglycemia. The arm swing exercise (ASE), a low-intensity exercise, is easy and convenient to perform without any equipment and is suitable for daily practice. Therefore, we aimed to investigate the effects of ASE on lung function and obesity in overweight T2DM patients. [Subjects and Methods] Twenty-four subjects continued their daily life routines for 8 weeks (control period), and then performed ASE for 8 weeks (30 minutes per day, 3 days per week) (ASE period). Pulmonary function tests were performed, and fasting blood glucose, haemoglobin A1c (HbA1c), lipid profiles, high-sensitive C-reactive protein (HSCRP), insulin concentration, and anthropometric parameters were measured before and after each period. [Results] After the ASE period, the forced vital capacity, forced expiratory volume in the first second of expiration, and maximal voluntary ventilation were increased when compared with after the control period. HbA1c, a low-density lipoprotein, malondialdehyde, oxidized glutathione, and the percent body fat were significantly decreased when compared with after the control period. However, other parameters, such as lung volume, anthropometric parameters, and fasting blood glucose, insulin, high-density lipoprotein, triglycerides, total cholesterol and glutathione concentrations, showed no differences between the two periods. [Conclusion] These data suggest that there is improvement of pulmonary functions in T2DM patients after ASE training.

Reduction of spasticity in cerebral palsy by anodal transcranial direct current stimulation.

OBJECTIVE: To evaluate the anti-spasticity effects of anodal transcranial direct current stimulation (tDCS) in individuals with spastic cerebral palsy (CP). MATERIAL AND METHOD: Forty-six children and adolescents with cerebral palsy were randomly assigned to either active (1 mA anodal) or sham (placebo) tDCS over the left primary motor cortex (Ml) on five consecutive days. Both group also received routine physical therapy. Measures of spasticity and passive range of motion (PROM) were administered before treatment, immediately after treatment, and at 24- and 48-hours follow-up. RESULTS: Participants assigned to active tDCS treatment evidenced significantly more pre- to immediately post-treatment reductions in spasticity than participants assigned to the sham (p = 0.004, p

Pain reduction in myofascial pain syndrome by anodal transcranial direct current stimulation combined with standard treatment: a randomized controlled study.

BACKGROUND: Myofascial pain syndrome (MPS) in the shoulder is among the most prevalent pain problems in the middle-aged population worldwide. Evidence suggests that peripheral and central sensitization may play an important role in the development and maintenance of shoulder MPS. Given previous research supporting the potential efficacy of anodal transcranial direct current stimulation (tDCS) for modulating pain-related brain activity in individuals with refractory central pain, we hypothesized that anodal tDCS when applied over the primary motor cortex (M1) combined with standard treatment will be more effective for reducing pain in patients with MPS than standard treatment alone. METHODS AND MATERIALS: Study participants were randomized to receive either (1) standard treatment with 5 consecutive days of 1 mA anodal tDCS over M1 for 20 minutes; or (2) standard treatment plus sham tDCS. Measures of pain intensity, shoulder passive range of motion (PROM), analgesic medication use, and self-reported physical functioning were administered before treatment and again at posttreatment and 1-, 2-, 3-, and 4-week follow-up. RESULTS: Thirty-one patients with MPS were enrolled. Participants assigned to the active tDCS condition reported significantly more pretreatment to posttreatment reductions in pain intensity that were maintained at 1-week posttreatment, and significant improvement in shoulder adduction PROM at 1-week follow-up than participants assigned to the sham tDCS condition. CONCLUSIONS: Five consecutive days of anodal tDCS over M1 combined with standard treatment appears to reduce pain intensity and may improve PROM, faster than standard treatment alone. Further tests on the efficacy and duration of effects of tDCS in the treatment of MPS are warranted.

Protein phosphatase 1 coordinates CFTR-dependent airway epithelial HCO3- secretion by reciprocal regulation of apical and basolateral membrane Cl(-)-HCO3- exchangers.

BACKGROUND AND PURPOSE: Our recent studies on human airway serous-like Calu-3 cells showed that cAMP agonists stimulated a HCO3(-) rich secretion containing up to 80 mM HCO3(-). This alkaline secretion relied on a coordinated switch in the activity of distinct Cl(-)-HCO3(-) anion exchangers (AE) located at different regions of the cell. At the apical membrane, cAMP agonists activated the electroneutral AE pendrin (SLC26A4), together with cystic fibrosis transmembrane conductance regulator (CFTR), while at the basolateral membrane the agonists inhibited AE2 (SLC4A2). However, the underlying mechanism(s) that orchestrates this cAMP-dependent switch in AE activity has not been elucidated. EXPERIMENTAL APPROACH: Apical and basolateral Cl(-)-HCO3(-) exchange was assessed by measuring Cl(-)-dependent changes in intracellular pH (pH(i)). KEY RESULTS: We show that protein phosphatase 1 (PP1), together with CFTR, play central roles in this reciprocal regulation of AE activity. Activation of pendrin by cAMP agonists, but not inhibition of the basolateral exchanger, was protein kinase A-dependent. Knocking down CFTR expression, or blocking its activity with GlyH-101, led to incomplete inhibition of the basolateral AE by cAMP, supporting a role for CFTR in this process. Addition of the PP1/2A inhibitor, okadaic acid, but not the PP2A specific inhibitor fostreicin, mimicked the effect of cAMP stimulation. Furthermore, okadaic acid-treated Calu-3 monolayers produced a more alkaline fluid than untreated cells, which was comparable with that produced by cAMP stimulation. CONCLUSIONS AND IMPLICATIONS: These results identify PP1 as a novel regulator of AE activity which, in concert with CFTR, coordinates events at both apical and basolateral membranes, crucial for efficient HCO3(-) secretion from Calu-3 cells.