High-definition Cathodal Direct Current Stimulation for Treatment of Acute Ischemic Stroke: A Randomized Clinical Trial.

Importance: Cathodal transcranial direct current stimulation (C-tDCS) provides neuroprotection in preclinical models of acute ischemic stroke (AIS) by inhibiting peri-infarct excitotoxic effects and enhancing collateral perfusion due to its vasodilatory properties. Objective: To report the first-in-human pilot study using individualized high-definition (HD) C-tDCS as a treatment of AIS. Design, Setting, and Participants: This randomized clinical trial was sham controlled with 3 + 3 dose escalation design, and was conducted at a single center from October 2018 to July 2021. Eligible participants were treated for AIS within 24 hours from onset, had imaging evidence of cortical ischemia with salvageable penumbra, and were ineligible for reperfusion therapies. HD C-tDCS electrode montage was selected for each patient to deliver the electric current to the ischemic region only. Patients were followed for 90 days. Main Outcomes and Measures: Primary outcomes were feasibility, assessed as time from randomization to study stimulation initiation; tolerability, assessed by rate of patients completing the full study stimulation period; and safety, assessed by rates of symptomatic intracranial hemorrhage at 24 hours. The efficacy imaging biomarkers of neuroprotection and collateral enhancement were explored. Results: A total of 10 patients with AIS were enrolled, 7 were randomized to active treatment and 3 to sham. Patient age was mean (SD) 75 (10) years old, 6 (60%) were female, and National Institutes of Health Stroke Scale score was mean (SD) 8 (7). Two doses of HD C-tDCS (1 milliamp [mA] for 20 minutes and 2 mA for 20 minutes) were studied. The speed of HD C-tDCS implementation was a median (IQR) 12.5 minutes (9-15 minutes) in the last 4 patients. Patients tolerated the HD C-tDCS with no permanent stimulation cessation. The hypoperfused region was reduced by a median (IQR) 100% (46% to 100%) in the active group vs increased by 325% (112% to 412%) in sham. Change in quantitative relative cerebral blood volume early poststimulation was a median (IQR) 64% (40% to 110%) in active vs -4% (-7% to 1%) sham patients and followed a dose-response pattern. Penumbral salvage in the active C-tDCS group was median (IQR) 66% (29% to 80.5%) vs 0% (IQR 0% to 0%) in sham. Conclusion and Relevance: In this randomized, first-in-human clinical trial, HD C-tDCS was started efficiently and well tolerated in emergency settings, with signals of beneficial effect upon penumbral salvage. These results support advancing HD C-tDCS to larger trials. Trial Registration: ClinicalTrials.gov Identifier: NCT03574038.

Limited output transcranial electrical stimulation 2023 (LOTES-2023): Updates on engineering principles, regulatory statutes, and industry standards for wellness, over-the-counter, or prescription devices with low risk.

The objective and scope of this Limited Output Transcranial Electrical Stimulation 2023 (LOTES-2023) guidance is to update the previous LOTES-2017 guidance. These documents should therefore be considered together. The LOTES provides a clearly articulated and transparent framework for the design of devices providing limited output (specified low-intensity range) transcranial electrical stimulation for a variety of intended uses. These guidelines can inform trial design and regulatory decisions, but most directly inform manufacturer activities - and hence were presented in LOTES-2017 as "Voluntary industry standard for compliance controlled limited output tES devices". In LOTES-2023 we emphasize that these standards are largely aligned across international standards and national regulations (including those in USA, EU, and South Korea), and so might be better understood as "Industry standards for compliance controlled limited output tES devices". LOTES-2023 is therefore updated to reflect a consensus among emerging international standards, as well as best available scientific evidence. "Warnings" and "Precautions" are updated to align with current biomedical evidence and applications. LOTES standards applied to a constrained device dose range, but within this dose range and for different use-cases, manufacturers are responsible to conduct device-specific risk management.

Quasi-static pipeline in electroconvulsive therapy computational modeling.

BACKGROUND: Computational models of current flow during Electroconvulsive Therapy (ECT) rely on the quasi-static assumption, yet tissue impedance during ECT may be frequency specific and change adaptively to local electric field intensity. OBJECTIVES: We systematically consider the application of the quasi-static pipeline to ECT under conditions where 1) static impedance is measured before ECT and 2) during ECT when dynamic impedance is measured. We propose an update to ECT modeling accounting for frequency-dependent impedance. METHODS: The frequency content on an ECT device output is analyzed. The ECT electrode-body impedance under low-current conditions is measured with an impedance analyzer. A framework for ECT modeling under quasi-static conditions based on a single device-specific frequency (e.g., 1 kHz) is proposed. RESULTS: Impedance using ECT electrodes under low-current is frequency dependent and subject specific, and can be approximated at >100 Hz with a subject-specific lumped parameter circuit model but at <100 Hz increased non-linearly. The ECT device uses a 2 µA 800 Hz test signal and reports a static impedance that approximate 1 kHz impedance. Combined with prior evidence suggesting that conductivity does not vary significantly across ECT output frequencies at high-currents (800-900 mA), we update the adaptive pipeline for ECT modeling centered at 1 kHz frequency. Based on individual MRI and adaptive skin properties, models match static impedance (at 2 µA) and dynamic impedance (at 900 mA) of four ECT subjects. CONCLUSIONS: By considering ECT modeling at a single representative frequency, ECT adaptive and non-adaptive modeling can be rationalized under a quasi-static pipeline.

Transcranial direct current stimulation during a prolonged cognitive task: the effect on cognitive and shooting performances in professional female basketball players.

The negative effect of prolonged cognitive demands on psychomotor skills in athletes has been demonstrated. Transcranial direct current stimulation (tDCS) could be used to mitigate this effect. This study examined the effects of tDCS over the left dorsolateral prefrontal cortex (DLPFC) during a 30-min inhibitory Stroop task on cognitive and shooting performances of professional female basketball players. Following a randomised, double-blinded, sham-controlled, cross-over design, players were assigned to receive anodal tDCS (a-tDCS, 2 mA for 20 min) or sham-tDCS in two different sessions. Data from 8 players were retained for analysis. Response Time decreased significantly over time (p < 0.001; partial η2 = 0.44; no effect of condition, or condition vs. time interaction). No difference in mean accuracy and shooting performance was observed between tDCS conditions. The results suggest that a-tDCS exert no additional benefits in reducing the negative effects of prolonged cognitive demands on technical performance compared to sham (placebo).Practitioner summary: Prolonged cognitive demands can negatively affect the athletes' performance. We tested whether transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (DLPFC) could attenuate these effects on cognitive and shooting performance in professional female basketball players. However, tDCS did not exert any additional benefits compared to sham.Abbreviations: tDCS: transcranial direct current stimulation; a-tDCS: anodal transcranial direct current stimulation; PFC: prefrontal cortex; DLPFC: dorsolateral prefrontal cortex; PCT: prolonged cognitive task; TT: time trial; RT: response time; NASA-TLX: National Aeronautics and Space Administration Task Load Index; RPE: ratings of perceived exertion; CR-10 scale: category rating scale; EEG: electroencephalogram; AU: arbitrary units.

Acute effect of high-definition and conventional tDCS on exercise performance and psychophysiological responses in endurance athletes: a randomized controlled trial.

Transcranial direct current stimulation (tDCS) has been used aiming to boost exercise performance and inconsistent findings have been reported. One possible explanation is related to the limitations of the so-called "conventional" tDCS, which uses large rectangular electrodes, resulting in a diffuse electric field. A new tDCS technique called high-definition tDCS (HD-tDCS) has been recently developed. HD-tDCS uses small ring electrodes and produces improved focality and greater magnitude of its aftereffects. This study tested whether HD-tDCS would improve exercise performance to a greater extent than conventional tDCS. Twelve endurance athletes (29.4 ± 7.3 years; 60.15 ± 5.09 ml kg-1 min-1) were enrolled in this single-center, randomized, crossover, and sham-controlled trial. To test reliability, participants performed two time to exhaustion (TTE) tests (control conditions) on a cycle simulator with 80% of peak power until volitional exhaustion. Next, they randomly received HD-tDCS (2.4 mA), conventional (2.0 mA), or active sham tDCS (2.0 mA) over the motor cortex for 20-min before performing the TTE test. TTE, heart rate (HR), associative thoughts, peripheral (lower limbs), and whole-body ratings of perceived exertion (RPE) were recorded every minute. Outcome measures were reliable. There was no difference in TTE between HD-tDCS (853.1 ± 288.6 s), simulated conventional (827.8 ± 278.7 s), sham (794.3 ± 271.2 s), or control conditions (TTE1 = 751.1 ± 261.6 s or TTE2 = 770.8 ± 250.6 s) [F(1.95; 21.4) = 1.537; P = 0.24; η2p = 0.123]. There was no effect on peripheral or whole-body RPE and associative thoughts (P > 0.05). No serious adverse effect was reported. A single session of neither HD-tDCS nor conventional tDCS changed exercise performance and psychophysiological responses in athletes, suggesting that a ceiling effect may exist.

Adaptive current-flow models of ECT: Explaining individual static impedance, dynamic impedance, and brain current density.

BACKGROUND: Improvements in electroconvulsive therapy (ECT) outcomes have followed refinement in device electrical output and electrode montage. The physical properties of the ECT stimulus, together with those of the patient's head, determine the impedances measured by the device and govern current delivery to the brain and ECT outcomes. OBJECTIVE: However, the precise relations among physical properties of the stimulus, patient head anatomy, and patient-specific impedance to the passage of current are long-standing questions in ECT research and practice. To this end, we develop a computational framework based on diverse clinical data sets. METHODS: We developed anatomical MRI-derived models of transcranial electrical stimulation (tES) that included changes in tissue conductivity due to local electrical current flow. These "adaptive" models simulate ECT both during therapeutic stimulation using high current (∼1 A) and when dynamic impedance is measured, as well as prior to stimulation when low current (∼1 mA) is used to measure static impedance. We modeled two scalp layers: a superficial scalp layer with adaptive conductivity that increases with electric field up to a subject-specific maximum (σSS¯), and a deep scalp layer with a subject-specific fixed conductivity (σDS). RESULTS: We demonstrated that variation in these scalp parameters may explain clinical data on subject-specific static impedance and dynamic impedance, their imperfect correlation across subjects, their relationships to seizure threshold, and the role of head anatomy. Adaptive tES models demonstrated that current flow changes local tissue conductivity which in turn shapes current delivery to the brain in a manner not accounted for in fixed tissue conductivity models. CONCLUSIONS: Our predictions that variation in individual skin properties, rather than other aspects of anatomy, largely govern the relationship between static impedance, dynamic impedance, and ECT current delivery to the brain, themselves depend on assumptions about tissue properties. Broadly, our novel modeling pipeline opens the door to explore how adaptive-scalp conductivity may impact transcutaneous electrical stimulation (tES).

Effect of Transcranial Direct Current Stimulation on Professional Female Soccer Players' Recovery Following Official Matches.

This study investigated the effect of transcranial direct current stimulation (tDCS) combined with a recovery training session on the well-being and self-perceived recovery of professional female soccer players after official matches. Data from 13 world-class players were analyzed after participating in four official soccer matches of the first division of the Brazilian Women's Soccer Championship (7-, 10-, and 13-day intervals). We applied anodal tDCS (a-tDCS) over the left dorsolateral prefrontal cortex with 2 mA for 20 minutes (+F3/-F4 montage) the day after each match. Participants underwent two randomly ordered sessions of a-tDCS or sham. Players completed the Well-Being Questionnaire (WBQ) and the Total Quality Recovery (TQR) scale before each experimental condition and again the following morning. A two-way repeated-measures ANOVA showed a significant time x condition interaction on the WBQ (F(1,11)=5.21; p=0.043; ηp2=0.32), but not on the TQR (F(1,12) = 0.552; p = 0.47; ηp2 = 0.044). There was a large effect size (ES) for a-tDCS for the WBQ score (ES = 1.02; 95%CI = 0.17;1.88), and there was a moderate WBQ score increase (ES = 0.53; 95%CI = -0.29;1.34) for the sham condition. We found similar increases in the TQR score for a-tDCS (ES = 1.50; 95%CI = 0.63-2.37) and the sham condition (ES = 1.36; 95%CI = 0.51-2.22). These results suggest that a-tDCS (+F3/-F4 montage) combined with a recovery training session may slightly improve perceived well-being beyond the level of improvement after only the recovery training session among world-class female soccer players. Prior to widely adopting this recovery approach, further study is needed with larger and more diverse samples, including for female teams of different performance levels.

Alternate sessions of transcranial direct current stimulation (tDCS) reduce chronic pain in women affected by chikungunya. A randomized clinical trial.

CONTEXT: Thousands of people worldwide have been infected by the chikungunya virus (CHIKV), and the persistence of joint pain symptoms has been considered the main problem. Neuromodulation techniques such as transcranial direct current stimulation (tDCS) act on brain areas involved in the processing of chronic pain. It was previously demonstrated that tDCS for five consecutive days significantly reduced pain in the chronic phase of chikungunya (CHIK). OBJECTIVE: To analyze the effect of alternate tDCS sessions on pain and functional capacity in individuals affected by CHIK. METHODS: In a randomized clinical trial, 58 women in the chronic phase of CHIK were divided into two groups: active-tDCS (M1-S0, 2 mA, 20 min) and sham-tDCS. The Visual Analogue Scale (VAS) and the Brief Pain Inventory (BPI) were used to assess pain, while the Health Assessment Questionnaire (HAQ) assessed functional capacity. These scales were used before and after six sessions of tDCS in nonconsecutive days on the primary motor cortex, and at follow-up consultation 7 and 15 days after the last session. A repeated measures mixed-model ANOVA was used for comparison between groups (significant p-values < 0.05). RESULTS: A significant pain reduction (Z [3, 171] = 14.303; p < 0.0001) was observed in the tDCS group compared to the sham group; no significant difference in functional capacity was observed (Z [1.57] = 2.797; p = 0.1). CONCLUSION: Our results suggest that six nonconsecutive sessions of active tDCS on M1 reduce pain in chronic CHIKV arthralgia.

Effect of tDCS on well-being and autonomic function in professional male players after official soccer matches.

This study aimed to examine the effect of transcranial direct current stimulation (tDCS) used as a recovery strategy, on heart rate (HR) measures and perceived well-being in 12 male professional soccer players. tDCS was applied in the days after official matches targeting the left dorsolateral prefrontal cortex (DLPFC) with 2 mA for 20 min (F3-F4 montage). Participants were randomly assigned to anodal tDCS (a-tDCS) or sham tDCS sessions. Players completed the Well-Being Questionnaire (WBQ) and performed the Submaximal Running Test (SRT) before and after tDCS. HR during exercise (HRex) was determined during the last 30 s of SRT. HR recovery (HRR) was recorded at 60 s after SRT. The HRR index was calculated from the absolute difference between HRex and HRR. A significant increase was observed for WBQ (effect of time; p<0.001; ηp2=0.417) with no effect for condition or interaction. A decrease in HRR (p = 0.014; ηp2=0.241), and an increase in HRR index were observed (p = 0.045; ηp2=0.168), with no effect for condition or interaction. No change for HRex was evident (p>0.05). These results suggest that a-tDCS over the DLPFC may have a positive effect on enhancing well-being and parasympathetic autonomic markers, which opens up a possibility for testing tDCS as a promising recovery-enhancing strategy targeting the brain in soccer players. The findings suggest that brain areas related to emotional and autonomic control might be involved in these changes with a possible interaction effect of tDCS by placebo-related effects, but more research is needed to verify this effect.

CHAOS Challenge - combined (CT-MR) healthy abdominal organ segmentation.

Segmentation of abdominal organs has been a comprehensive, yet unresolved, research field for many years. In the last decade, intensive developments in deep learning (DL) introduced new state-of-the-art segmentation systems. Despite outperforming the overall accuracy of existing systems, the effects of DL model properties and parameters on the performance are hard to interpret. This makes comparative analysis a necessary tool towards interpretable studies and systems. Moreover, the performance of DL for emerging learning approaches such as cross-modality and multi-modal semantic segmentation tasks has been rarely discussed. In order to expand the knowledge on these topics, the CHAOS - Combined (CT-MR) Healthy Abdominal Organ Segmentation challenge was organized in conjunction with the IEEE International Symposium on Biomedical Imaging (ISBI), 2019, in Venice, Italy. Abdominal organ segmentation from routine acquisitions plays an important role in several clinical applications, such as pre-surgical planning or morphological and volumetric follow-ups for various diseases. These applications require a certain level of performance on a diverse set of metrics such as maximum symmetric surface distance (MSSD) to determine surgical error-margin or overlap errors for tracking size and shape differences. Previous abdomen related challenges are mainly focused on tumor/lesion detection and/or classification with a single modality. Conversely, CHAOS provides both abdominal CT and MR data from healthy subjects for single and multiple abdominal organ segmentation. Five different but complementary tasks were designed to analyze the capabilities of participating approaches from multiple perspectives. The results were investigated thoroughly, compared with manual annotations and interactive methods. The analysis shows that the performance of DL models for single modality (CT / MR) can show reliable volumetric analysis performance (DICE: 0.98 ± 0.00 / 0.95 ± 0.01), but the best MSSD performance remains limited (21.89 ± 13.94 / 20.85 ± 10.63 mm). The performances of participating models decrease dramatically for cross-modality tasks both for the liver (DICE: 0.88 ± 0.15 MSSD: 36.33 ± 21.97 mm). Despite contrary examples on different applications, multi-tasking DL models designed to segment all organs are observed to perform worse compared to organ-specific ones (performance drop around 5%). Nevertheless, some of the successful models show better performance with their multi-organ versions. We conclude that the exploration of those pros and cons in both single vs multi-organ and cross-modality segmentations is poised to have an impact on further research for developing effective algorithms that would support real-world clinical applications. Finally, having more than 1500 participants and receiving more than 550 submissions, another important contribution of this study is the analysis on shortcomings of challenge organizations such as the effects of multiple submissions and peeking phenomenon.

Impact of brain atrophy on tDCS and HD-tDCS current flow: a modeling study in three variants of primary progressive aphasia.

BACKGROUND: During transcranial direct current stimulation (tDCS), the amount and distribution of current that reaches the brain depends on individual anatomy. Many progressive neurodegenerative diseases are associated with cortical atrophy, but the importance of individual brain atrophy during tDCS in patients with progressive atrophy, including primary progressive aphasia (PPA), remains unclear. OBJECTIVE: In the present study, we addressed the question whether brain anatomy in patients with distinct cortical atrophy patterns would impact brain current intensity and distribution during tDCS over the left IFG. METHOD: We developed state-of-the-art, gyri-precise models of three subjects, each representing a variant of primary progressive aphasia: non-fluent variant PPA (nfvPPA), semantic variant PPA (svPPA), and logopenic variant PPA (lvPPA). We considered two exemplary montages over the left inferior frontal gyrus (IFG): a conventional pad montage (anode over F7, cathode over the right cheek) and a 4 × 1 high-definition tDCS montage. We further considered whether local anatomical features, specifically distance of the cortex to skull, can directly predict local electric field intensity. RESULTS: We found that the differences in brain current flow across the three PPA variants fall within the distribution of anatomically typical adults. While clustering of electric fields was often around individual gyri or sulci, the minimal distance from the gyri/sulci to skull was not correlated with electric field intensity. CONCLUSION: Limited to the conditions and assumptions considered here, this argues against a specific need to adjust the tDCS montage for these patients any more than might be considered useful in anatomically typical adults. Therefore, local atrophy does not, in isolation, reliably predict local electric field. Rather, our results are consistent with holistic head anatomy influencing brain current flow, with tDCS producing diffuse and individualized brain current flow patterns and HD-tDCS producing targeted brain current flow across individuals.

Comparison of semi-automatic and deep learning-based automatic methods for liver segmentation in living liver transplant donors.

PURPOSE: To compare the accuracy and repeatability of emerging machine learning based (i.e. deep) automatic segmentation algorithms with those of well-established semi-automatic (interactive) methods for determining liver volume in living liver transplant donors at computerized tomography (CT) imaging. METHODS: A total of 12 (6 semi-, 6 full-automatic) methods are evaluated. The semi-automatic segmentation algorithms are based on both traditional iterative models including watershed, fast marching, region growing, active contours and modern techniques including robust statistical segmenter and super-pixels. These methods entail some sort of interaction mechanism such as placing initialization seeds on images or determining a parameter range. The automatic methods are based on deep learning and they include three framework templates (DeepMedic, NiftyNet and U-Net) the first two of which are applied with default parameter sets and the last two involve adapted novel model designs. For 20 living donors (6 training and 12 test datasets), a group of imaging scientists and radiologists created ground truths by performing manual segmentations on contrast material-enhanced CT images. Each segmentation is evaluated using five metrics (i.e. volume overlap and relative volume errors, average/RMS/maximum symmetrical surface distances). The results are mapped to a scoring system and a final grade is calculated by taking their average. Accuracy and repeatability were evaluated using slice by slice comparisons and volumetric analysis. Diversity and complementarity are observed through heatmaps. Majority voting and Simultaneous Truth and Performance Level Estimation (STAPLE) algorithms are utilized to obtain the fusion of the individual results. RESULTS: The top four methods are determined to be automatic deep models having 79.63, 79.46 and 77.15 and 74.50 scores. Intra-user score is determined as 95.14. Overall, deep automatic segmentation outperformed interactive techniques on all metrics. The mean volume of liver of ground truth is found to be 1409.93 mL ± 271.28 mL, while it is calculated as 1342.21 mL ± 231.24 mL using automatic and 1201.26 mL ± 258.13 mL using interactive methods, showing higher accuracy and less variation on behalf of automatic methods. The qualitative analysis of segmentation results showed significant diversity and complementarity enabling the idea of using ensembles to obtain superior results. The fusion of automatic methods reached 83.87 with majority voting and 86.20 using STAPLE that are only slightly less than fusion of all methods that achieved 86.70 (majority voting) and 88.74 (STAPLE). CONCLUSION: Use of the new deep learning based automatic segmentation algorithms substantially increases the accuracy and repeatability for segmentation and volumetric measurements of liver. Fusion of automatic methods based on ensemble approaches exhibits best results almost without any additional time cost due to potential parallel execution of multiple models.

Effects of 6-month at-home transcranial direct current stimulation on cognition and cerebral glucose metabolism in Alzheimer's disease.

BACKGROUND: Although single or multiple sessions of transcranial direct current stimulation (tDCS) on the prefrontal cortex over a few weeks improved cognition in patients with Alzheimer's disease (AD), effects of repeated tDCS over longer period and underlying neural correlates remain to be elucidated. OBJECTIVE: This study investigated changes in cognitive performances and regional cerebral metabolic rate for glucose (rCMRglc) after administration of prefrontal tDCS over 6 months in early AD patients. METHODS: Patients with early AD were randomized to receive either active (n = 11) or sham tDCS (n = 7) over the dorsolateral prefrontal cortex (DLPFC) at home every day for 6 months (anode F3/cathode F4, 2 mA for 30 min). All patients underwent neuropsychological tests and brain 18F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) scans at baseline and 6-month follow-up. Changes in cognitive performances and rCMRglc were compared between the two groups. RESULTS: Compared to sham tDCS, active tDCS improved global cognition measured with Mini-Mental State Examination (p for interaction = 0.02) and language function assessed by Boston Naming Test (p for interaction = 0.04), but not delayed recall performance. In addition, active tDCS prevented decreases in executive function at a marginal level (p for interaction < 0.10). rCMRglc in the left middle/inferior temporal gyrus was preserved in the active group, but decreased in the sham group (p for interaction < 0.001). CONCLUSIONS: Daily tDCS over the DLPFC for 6 months may improve or stabilize cognition and rCMRglc in AD patients, suggesting the therapeutic potential of repeated at-home tDCS.

Anncolvar: Approximation of Complex Collective Variables by Artificial Neural Networks for Analysis and Biasing of Molecular Simulations.

The state of a molecular system can be described in terms of collective variables. These low-dimensional descriptors of molecular structure can be used to monitor the state of the simulation, to calculate free energy profiles or to accelerate rare events by a bias potential or a bias force. Frequent calculation of some complex collective variables may slow down the simulation or analysis of trajectories. Moreover, many collective variables cannot be explicitly calculated for newly sampled structures. In order to address this problem, we developed a new package called anncolvar. This package makes it possible to build and train an artificial neural network model that approximates a collective variable. It can be used to generate an input for the open-source enhanced sampling simulation PLUMED package, so the collective variable can be monitored and biased by methods available in this program. The computational efficiency and the accuracy of anncolvar are demonstrated on selected molecular systems (cyclooctane derivative, Trp-cage miniprotein) and selected collective variables (Isomap, molecular surface area).

Effects of Transcranial Direct Current Stimulation With Caffeine Intake on Muscular Strength and Perceived Exertion.

Lattari, E, Vieira, LAF, Oliveira, BRR, Unal, G, Bikson, M, de Mello Pedreiro, RC, Marques Neto, SR, Machado, S, and Maranhão-Neto, GA. Effects of transcranial direct current stimulation with caffeine intake on muscular strength and perceived exertion. J Strength Cond Res 33(5): 1237-1243, 2019-The aim of this study was to investigate the acute effects of transcranial direct current stimulation (tDCS) associated with caffeine intake on muscular strength and ratings of perceived exertion (RPE). Fifteen healthy young males recreationally trained (age: 25.3 ± 3.2 years, body mass: 78.0 ± 6.9 kg, height: 174.1 ± 6.1 cm) were recruited. The experimental conditions started with the administration of caffeine (Caff) or placebo (Pla) 1 hour before starting the anodal tDCS (a-tDCS or sham). There was an intake of 5 mg·kg of Caff or 5 mg·kg of Pla. After the intake, a-tDCS or sham was applied in the left dorsolateral prefrontal cortex with intensity of 2 mA and 20 minutes of duration. The experimental conditions were defined as Sham + Pla, a-tDCS + Pla, Sham + Caff, and a-tDCS + Caff. After the conditions, muscular strength and RPE were verified. Muscular strength was determined by volume load performed in bench press exercise. Muscular strength in Sham + Pla condition was lower compared with all others conditions (p < 0.05). The RPE in the Sham + Pla was greater compared with a-tDCS + Caff (p < 0.05). Muscular strength was greater in all experimental conditions, and a-tDCS + Caff had lower RPE compared with placebo. When very little gains in muscle strength are expected, both caffeine and tDCS were effective in increasing muscle strength. Besides, the improvement in RPE of the caffeine associated with a-tDCS could prove advantageous in participants experienced in strength training. In fact, coaches and applied sport scientists quantitating the intensity of training based on RPE.

Effect of transcranial direct current stimulation on exercise performance: A systematic review and meta-analysis.

BACKGROUND: Transcranial direct current stimulation (tDCS) has been used to improve exercise performance, though the protocols used, and results found are mixed. OBJECTIVE: We aimed to analyze the effect of tDCS on improving exercise performance. METHODS: A systematic search was performed on the following databases, until December 2017: PubMed/MEDLINE, Embase, Web of Science, SCOPUS, and SportDiscus. Full-text articles that used tDCS for exercise performance improvement in adults were included. We compared the effect of anodal (anode near nominal target) and cathodal (cathode near nominal target) tDCS to a sham/control condition on the outcome measure (performance in isometric, isokinetic or dynamic strength exercise and whole-body exercise). RESULTS: 22 studies (393 participants) were included in the qualitative synthesis and 11 studies (236 participants) in the meta-analysis. The primary motor cortex (M1) was the main nominal tDCS target (n = 16; 72.5%). A significant effect favoring anodal tDCS (a-tDCS) applied before exercise over M1 was found on cycling time to exhaustion (mean difference = 93.41 s; 95%CI = 27.39 s-159.43 s) but this result was strongly influenced by one study (weight = 84%), no effect was found for cathodal tDCS (c-tDCS). No significant effect was found for a-tDCS applied on M1 before or during exercise on isometric muscle strength of the upper or lower limbs. Studies regarding a-tDCS over M1 on isokinetic muscle strength presented mixed results. Individual results of studies using a-tDCS applied over the prefrontal and motor cortices either before or during dynamic muscle strength testing showed positive results, but performing meta-analysis was not possible. CONCLUSION: For the protocols tested, a-tDCS but not c-tDCS vs. sham over M1 improved exercise performance in cycling only. However, this result was driven by a single study, which when removed was no longer significant. Further well-controlled studies with larger sample sizes and broader exploration of the tDCS montages and doses are warranted.

Automatic M1-SO Montage Headgear for Transcranial Direct Current Stimulation (TDCS) Suitable for Home and High-Throughput In-Clinic Applications.

OBJECTIVES: Non-invasive transcranial direct current stimulation (tDCS) over the motor cortex is broadly investigated to modulate functional outcomes such as motor function, sleep characteristics, or pain. The most common montages that use two large electrodes (25-35 cm2 ) placed over the area of motor cortex and contralateral supraorbital region (M1-SO montages) require precise measurements, usually using the 10-20 EEG system, which is cumbersome in clinics and not suitable for applications by patients at home. The objective was to develop and test novel headgear allowing for reproduction of the M1-SO montage without the 10-20 EEG measurements, neuronavigation, or TMS. MATERIALS AND METHODS: Points C3/C4 of the 10-20 EEG system is the conventional reference for the M1 electrode. The headgear was designed using an orthogonal, fixed-angle approach for connection of frontal and coronal headgear components. The headgear prototype was evaluated for accuracy and replicability of the M1 electrode position in 600 repeated measurements compared to manually determined C3 in 30 volunteers. Computational modeling was used to estimate brain current flow at the mean and maximum recorded electrode placement deviations from C3. RESULTS: The headgear includes navigational points for accurate placement and assemblies to hold electrodes in the M1-SO position without measurement by the user. Repeated measurements indicated accuracy and replicability of the electrode position: the mean [SD] deviation of the M1 electrode (size 5 × 5 cm) from C3 was 1.57 [1.51] mm, median 1 mm. Computational modeling suggests that the potential deviation from C3 does not produce a significant change in brain current flow. CONCLUSIONS: The novel approach to M1-SO montage using a fixed-angle headgear not requiring measurements by patients or caregivers facilitates tDCS studies in home settings and can replace cumbersome C3 measurements for clinical tDCS applications.

Neuromodulation treats Chikungunya arthralgia: a randomized controlled trial.

The Chikungunya (CHIK) virus is epidemic in Brazil, with 170,000 cases in the first half of 2016. More than 60% of patients present relapsing and remitting chronic arthralgia with debilitating pain lasting years. There are no specific therapeutic agents to treat and rehabilitee infected persons with CHIK. Persistent pain can lead to incapacitation, requiring long-term pharmacological treatment. Advances in non-pharmacological treatments are necessary to promote pain relief without side effects and to restore functionality. Clinical trials indicate transcranial direct current stimulation (tDCS) can treat a broad range of chronic pain disorders, including diffuse neuromuscular pain and arthralgia. Here, we demonstrate that the tDCS across the primary motor cortex significantly reduces pain in the chronic phase of CHIK. High-resolution computational model was created to analyze the cortical electric field generated during tDCS and a diffuse and clustered brain current flow including M1 ipsilateral and contralateral, left DLPFC, nucleus accumbens, and cingulate was found. Our findings suggest tDCS could be an effective, inexpensive and deployable therapy to areas lacking resources with a significant number of patients with chronic CHIK persistent pain.

Asymmetric Orientation Distribution Functions (AODFs) revealing intravoxel geometry in diffusion MRI.

Characterization of anisotropy via diffusion MRI reveals fiber crossings in a substantial portion of voxels within the white-matter (WM) regions of the human brain. A considerable number of such voxels could exhibit asymmetric features such as bends and junctions. However, widely employed reconstruction methods yield symmetric Orientation Distribution Functions (ODFs) even when the underlying geometry is asymmetric. In this paper, we employ inter-voxel directional filtering approaches through a cone model to reveal more information regarding the cytoarchitectural organization within the voxel. The cone model facilitates a sharpening of the ODFs in some directions while suppressing peaks in other directions, thus yielding an Asymmetric ODF (AODF) field. We also show that a scalar measure of AODF asymmetry can be employed to obtain new contrast within the human brain. The feasibility of the technique is demonstrated on in vivo data obtained from the MGH-USC Human Connectome Project (HCP) and Parkinson's Progression Markers Initiative (PPMI) Project database. Characterizing asymmetry in neural tissue cytoarchitecture could be important for localizing and quantitatively assessing specific neuronal pathways.

Neighborhood resolved fiber orientation distributions (NRFOD) in automatic labeling of white matter fiber pathways.

Accurate digital representation of major white matter bundles in the brain is an important goal in neuroscience image computing since the representations can be used for surgical planning, intra-patient longitudinal analysis and inter-subject population connectivity studies. Reconstructing desired fiber bundles generally involves manual selection of regions of interest by an expert, which is subject to user bias and fatigue, hence an automation is desirable. To that end, we first present a novel anatomical representation based on Neighborhood Resolved Fiber Orientation Distributions (NRFOD) along the fibers. The resolved fiber orientations are obtained by generalized q-sampling imaging (GQI) and a subsequent diffusion decomposition method. A fiber-to-fiber distance measure between the proposed fiber representations is then used in a density-based clustering framework to select the clusters corresponding to the major pathways of interest. In addition, neuroanatomical priors are utilized to constrain the set of candidate fibers before density-based clustering. The proposed fiber clustering approach is exemplified on automation of the reconstruction of the major fiber pathways in the brainstem: corticospinal tract (CST); medial lemniscus (ML); middle cerebellar peduncle (MCP); inferior cerebellar peduncle (ICP); superior cerebellar peduncle (SCP). Experimental results on Human Connectome Project (HCP)'s publicly available "WU-Minn 500 Subjects + MEG2 dataset" and expert evaluations demonstrate the potential of the proposed fiber clustering method in brainstem white matter structure analysis.