mA Stimulation Research Articles

Electroacupuncture inhibited carrageenan-induced pain aversion by activating GABAergic neurons in the ACC

Pain aversion is an avoidance response to painful stimuli. Previous research has indicated that the anterior cingulate cortex (ACC) is involved in pain aversion processing. However, as interneurons, the role of GABAergic neurons in the ACC (GABAACC neurons) in pain aversion is still unclear. Electroacupuncture (EA) has been shown to ameliorate pain aversion, but the mechanism is not clarified. The present study provided evidence that inhibition of GABAACC neurons contributed to pain aversion. EA alleviated pain aversion by activating GABAACC neurons in an intensity-dependent manner. Specifically, 0.3 mA EA stimulation showed better effects on pain aversion than 0.1 mA stimulation, which could be reversed by chemical genetic inhibition of GABAACC neurons. These results provide a novel mechanism by which EA alleviates pain aversion by reversing GABAACC neurons.

Effect of Transcranial Direct Current Stimulation on Craving, Cognitive Functions, and Serum Brain-Derived Neurotrophic Factor Level in Individuals on Maintenance Treatment for Opioid Use Disorder, A Randomized Sham-Controlled Trial.

To investigate the effects of transcranial direct current stimulation (tDCS) on brain-derived neurotrophic factor (BDNF) levels, craving, and executive functions in individuals on maintenance treatment for opioid use. We randomized 70 right-handed men aged 18-55 years into 2 groups: the intervention group and the sham group. The intervention was 10 sessions of 2 mA stimulation over 5 days. Each session in the sham group ended after 30 seconds. Craving was measured using the Desire for Drug Questionnaire (DDQ), Obsessive Compulsive Drug Use Scale (OCDUS), and visual analog scale (VAS). The measurements were taken before and after the intervention, as well as 2 months later. BDNF was measured before and after the intervention. Repeated-measures analysis of variance, the generalized estimating equation model, and independent t test were used for data analysis. The mean differences (95% confidence intervals) in pre and post craving scores in the intervention group were (12.71 [9.10 to 16.32], P = 0.167) for VAS, (1.54 [1.12 to 1.96], P = 0.012) for OCDUS, and (1.71 [1.27 to 2.15], P = 0.125) for DDQ. These measures in the control group were -0.44 (-1.19 to 0.30), 0.01 (-0.21 to 0.23), and 0.126 (-0.11 to 0.36), respectively. BDNF serum levels significantly increased after the intervention (difference, 0.84 [0.69 to 0.99], P < 0.001); however, this change was not significant in the generalized estimating equation model. The effect of tDCS on craving was significant in OCDUS, but not significant in VAS and DDQ. The tDCS reduces craving and improves executive functions in the short term. BDNF serum level was not associated with tDCS.

Consecutive Dual-Session Transcranial Direct Current Stimulation in Chronic Subjective Severe to Catastrophic Tinnitus with Normal Hearing.

Transcranial direct current stimulation (tDCS) is emerging as a promising non-invasive intervention for tinnitus by aiming to modulate abnormal brain activity. This study investigated the efficacy of dual-session tDCS for the relief of perception, distress, and loudness in patients with severe chronic subjective tinnitus and assessed the duration of tinnitus suppression effects compared to single-session and control groups over a 2-month follow-up. In a prospective, randomized, single-blind, placebo-controlled trial, 30 participants with severe chronic subjective tinnitus underwent bifrontal tDCS. The control group (n = 9), single-session group (n = 10), and dual-session group (n = 11) received 2 mA stimulation for 20 min per session, twice a week for one month. The treatment response was monitored weekly using the Visual Analogue Scale (VAS), with additional assessments using the Tinnitus Handicap Inventory (THI) and Beck Depression Inventory (BDI) at the fourth and eighth weeks. The single- and dual-session groups showed statistically significant improvements in VAS, THI, and BDI scores compared to the control group. THI and BDI scores showed a significant difference between the single- and dual-session groups. The dual-session group demonstrated a more sustained tinnitus suppression effect than the single-session group. tDCS has been validated as an effective intervention for the suppression of tinnitus, with the dual-session protocol showing longer-term benefits. These findings support the potential of tDCS as a treatment for tinnitus, particularly in dual-session applications.

Neurochemical Predictors of Generalized Learning Induced by Brain Stimulation and Training.

Methods of cognitive enhancement for humans are most impactful when they generalize across tasks. However, the extent to which such "transfer" is possible via interventions is widely debated. In addition, the contribution of excitatory and inhibitory processes to such transfer is unknown. Here, in a large-scale neuroimaging individual differences study with humans (both sexes), we paired multitasking training and noninvasive brain stimulation (transcranial direct current stimulation, tDCS) over multiple days and assessed performance across a range of paradigms. In addition, we varied tDCS dosage (1.0 and 2.0 mA), electrode montage (left or right prefrontal regions), and training task (multitasking vs a control task) and assessed GABA and glutamate concentrations via ultrahigh field 7T magnetic resonance spectroscopy. Generalized benefits were observed in spatial attention, indexed by visual search performance, when multitasking training was combined with 1.0 mA stimulation targeting either the left or right prefrontal cortex (PFC). This transfer effect persisted for ∼30 d post intervention. Critically, the transferred benefits associated with right prefrontal tDCS were predicted by pretraining concentrations of glutamate in the PFC. Thus, the effects of this combined stimulation and training protocol appear to be linked predominantly to excitatory brain processes.

Beta tACS of varying intensities differentially affect resting-state and movement-related M1-M1 connectivity.

Due to the interconnected nature of the brain, changes in one region are likely to affect other structurally and functionally connected regions. Emerging evidence indicates that single-site transcranial alternating current stimulation (tACS) can modulate functional connectivity between stimulated and interconnected unstimulated brain regions. However, our understanding of the network response to tACS is incomplete. Here, we investigated the effect of beta tACS of different intensities on phase-based connectivity between the left and right primary motor cortices in 21 healthy young adults (13 female; mean age 24.30 ± 4.84 years). Participants underwent four sessions of 20 min of 20 Hz tACS of varying intensities (sham, 0.5 mA, 1.0 mA, or 1.5 mA) applied to the left primary motor cortex at rest. We recorded resting-state and event-related electroencephalography (EEG) before and after tACS, analyzing changes in sensorimotor beta (13-30 Hz) imaginary coherence (ImCoh), an index of functional connectivity. Event-related EEG captured movement-related beta activity as participants performed self-paced button presses using their right index finger. For resting-state connectivity, we observed intensity-dependent changes in beta ImCoh: sham and 0.5 mA stimulation resulted in an increase in beta ImCoh, while 1.0 mA and 1.5 mA stimulation decreased beta ImCoh. For event-related connectivity, 1.5 mA stimulation decreased broadband ImCoh (4-90 Hz) during movement execution. None of the other stimulation intensities significantly modulated event-related ImCoh during movement preparation, execution, or termination. Interestingly, changes in ImCoh during movement preparation following 1.0 mA and 1.5 mA stimulation were significantly associated with participants' pre-tACS peak beta frequency, suggesting that the alignment of stimulation frequency and peak beta frequency affected the extent of neuromodulation. Collectively, these results suggest that beta tACS applied to a single site influences connectivity within the motor network in a manner that depends on the intensity and frequency of stimulation. These findings have significant implications for both research and clinical applications.

Neurocognitive effects of 3 mA prefrontal electrical stimulation in schizophrenia: A randomized sham-controlled tDCS-fMRI study protocol.

Schizophrenia (SCZ) is characterized by cognitive deficits that are linked to prefrontal cortex dysfunction. While transcranial direct current stimulation (tDCS) shows promise for improving cognition, the effects of intensified 3mA tDCS protocols on brain physiology are unknown. This project aims to elucidate the neurophysiological and cognitive effects of an intensified prefrontal tDCS protocol in SCZ. The study is designed as a randomized, double-blind, 2-arm parallel-group, sham-controlled, trial. Forty-eight participants with SCZ and cognitive impairment (measured via a set of executive functions tests) will be randomly allocated to receive either a single session of active (n = 24) or sham (n = 24) tDCS (20-min, 3-mA). The anodal and cathodal electrodes are positioned over the left and right DLPFC respectively. The stimulation occurs concurrently with the working memory task, which is initiated precisely 5 minutes after the onset of tDCS. Structural and resting-state (rs-fMRI) scans are conducted immediately before and after both active and sham tDCS using a 3 Tesla scanner (Siemens Prisma model) equipped with a 64-channel head coil. The primary outcome will be changes in brain activation (measures vis BOLD response) and working memory performance (accuracy, reaction time). The results of this study are helpful in optimizing tDCS protocols in SCZ and inform us of neurocognitive mechanisms underlying 3 mA stimulation. This study will additionally provide initial safety and efficacy data on a 3 mA tDCS protocol to support larger clinical trials. Positive results could lead to rapid and broader testing of a promising tool for debilitating symptoms that affect the majority of patients with SCZ. The results will be made available through publications in peer-reviewed journals and presentations at national and international conferences.

Effects of Transcranial Direct Current Stimulation on Motor and Cognitive Dysfunction in an Experimental Traumatic Brain Injury Model.

To investigate the therapeutic and neuroprotective effects of transcranial direct current stimulation (tDCS) application on the traumatic brain injury (TBI)-induced glutamate and calcium excitotoxicity and loss of motor and cognitive functions. Forty rats were equally divided in the sham, TBI, tDCS + TBI + tDCS, and TBI + tDCS groups. Mild TBI was induced by dropping a 450-g iron weight from a height of 1 m onto the skull of the rats. The tDCS + TBI + tDCS group was prophylactically administered 1 mA stimulation for 30 min for 7 days starting 5 days before inducing TBI. In the TBI + tDCS group, tDCS (1 mA for 30 min) was administered 2 h after TBI, on days 1 and 2. Cognitive and locomotor functions were assessed using the novel object recognition and open field tests. The calcium, glutamate, and N-methyl-D-aspartate receptor 1 (NMDAR1) levels in the hippocampus were measured using enzyme-linked immunosorbent assay. Although the motor and cognitive functions were substantially reduced in the TBI group when compared with the sham, they improved in the treatment groups (p < 0.05). The calcium, glutamate, and NMDAR1 levels were considerably higher in the TBI group than in the sham (p < 0.001). However, they were considerably lower in the tDCS + TBI + tDCS and TBI + tDCS groups than in the TBI groups (p < 0.05). In particular, the change in the tDCS + TBI + tDCS group was higher than that in the TBI + tDCS group. Application of tDCS before the development of TBI improved motor and cognitive dysfunction. It demonstrated a neuroprotective and therapeutic effect by reducing the excitotoxicity via the regulation of calcium and glutamate levels.

Transspinal Direct Current Electrical Stimulation Selectively Affects the Excitability of the Corticospinal System, Depending on the Intensity but Not Motor Skills.

Transspinal direct current stimulation (tsDCS) is a non-invasive technique used to modulate spinal cord activity. However, the effects and mechanisms of this stimulation are currently not comprehensively known. This study aimed to estimate the effect of different intensities of tsDCS applied at the level of cervical enlargement of the spinal cord (C7-Th1 segments) on the excitability of the corticospinal system (CSS) and the correction of motor skills in healthy subjects. The effect of tsDCS was estimated by the motor-evoked potentials (MEP) elicited by transcranial magnetic stimulation (TMS) in the primary motor cortex (M1). The study involved 54 healthy adults aged 22 ± 4 years. The application of 11 min anodal tsDCS at the level of the cervical spine C7-Th1 with a current intensity of 2.5 mA did not change the MEP amplitude of the upper limb muscles, in contrast to the data that we previously obtained with a current intensity of 1.5 mA. We also found no difference in the effect of 2.5 mA stimulation on motor skill correction in healthy subjects in the nine-hole peg test (9-HPT) and the serial reaction time task (SRT) as with 1.5 mA stimulation. Our data show that an increase in the intensity of stimulation does not lead to an increase in the effects but rather reduces the effects of stimulation. These results provide information about the optimally appropriate stimulation current intensities to induce CSS excitability and the ability of tsDCS to influence motor skills in healthy adults.

The intensity of transspinal direct current stimulation affects the excitability of the corticospinal system

BACKGROUND: Transspinal direct current stimulation (tsDCS) affects the corticospinal system, one of the central human systems associated with controlling precise voluntary movements. Stimulation effects are very sensitive to montage and protocols of applied stimulation because they can involve different neuronal mechanisms. AIM: This study aimed to estimate the effects of parameters of anodal tsDCS applied at the level of the spinal cord (C7–Th1 segments) with cervical enlargement to determine the excitability of the corticospinal system and the correction of motor skills in healthy people. METHODS: The study involved 81 healthy adults aged 21.19±3.20 years. The effect of tsDCS was assessed using motor-evoked potentials from the first dorsal interosseous (FDI) muscle by transcranial magnetic stimulation in the primary motor cortex before stimulation, immediately after stimulation, and after 15 min. RESULTS: The application of 11-min anodal tsDCS at the C7–Th1 level with a current of 1.5 mA affects the FDI muscle, initially reducing the amplitude of transcranial magnetic stimulation induced motor-evoked potentials immediately after stimulation. The amplitude of the motor-evoked potentials increases after 15 min of stimulation. tsDCS with an intensity of 2.5 mA does not affect the change in the amplitude of motor-evoked potentials. Similarly, no difference was found in the effect of 1.5 mA stimulation on the correction of motor skills in healthy adults at the nine-hole peg test and the serial reaction time task as with 2.5 mA. CONCLUSION: This study adds information about the optimally appropriate current intensities of stimulation to induce corticospinal system excitability and the ability of tsDCS to influence motor skills in healthy adults.

Transcranial direct current stimulation as treatment for major depression in a home treatment setting (HomeDC trial): study protocol and methodology of a double-blind, placebo-controlled pilot study

IntroductionTranscranial direct current stimulation (tDCS) of prefrontal cortex regions has been reported to exert therapeutic effects in patients with major depressive disorder (MDD). Due to its beneficial safety profile, its easy mode of application, and its cost-effectiveness, tDCS has recently been proposed for treatment at home. This would offer new chances for regionally widespread and long-term application. However, tDCS at home must meet the new methodological challenges of handling and adherence. At the same time, data from randomized controlled trials (RCT) investigating this mode of application are still lacking. In this pilot RCT, we therefore investigate the feasibility, safety, and effectiveness of a new antidepressant tDCS application set-up.Methods and analysisThe HomeDC trial will be conducted as a double-blind, placebo-controlled, parallel-group design trial. Thirty-two study participants with MDD will be randomly assigned to active or sham tDCS groups. Participants will self-administer prefrontal tDCS for 6 weeks. Active tDCS will be conducted with anode over F3, cathode over F4, for 5 sessions/week, with a duration of 30 min/day, and 2 mA stimulation intensity. Sham tDCS, conversely, follows an identical protocol in regard to electrode montage and timing, but with no electric stimulation between the ramp-in and ramp-out periods. Both conditions will be administered either as a monotherapy or an adjunctive treatment to a stable dose of antidepressant medication. Adjunctive magnetic resonance imaging (MRI) and electric field (E-field) modelling will be conducted at baseline. Primary outcome is feasibility based on successfully completed stimulations and drop-out rates. The intervention is considered feasible when 20 out of 30 sessions have been fully conducted by at least 75% of the participants. Effectiveness and safety will be assessed as secondary outcomes.DiscussionIn the HomeDC trial, the technical requirements for a placebo-controlled tDCS study in a home-based treatment setting have been established. The trial addresses the crucial points of the home-based tDCS treatment approach: uniform electrode positioning, frequent monitoring of stimulation parameters, adherence, and ensuring an appropriate home treatment environment. This study will further identify constraints and drawbacks of this novel mode of treatment.Trial registrationwww.ClinicalTrials.gov. Trial registration number: NCT05172505. Registration date: 12/13/2021.

Early electroacupuncture intervention delays progression of disease in mice with amyotrophic lateral sclerosis by down-regulating TLR4/NF-κB signaling

To observe the effect of early electroacupuncture (EA) intervention on Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway in mice with amyotrophic lateral sclerosis (ALS), so as to explore its mechanisms underlying alleviation of ALS. Fifty-four ALS (ALS-SOD1G93A) mice with SOD1G93A gene mutation identified by PCR were randomly divided into model group, 60 day(d) EA group and 90 d EA group(n=18 mice in each group), and other 18 ALS-SOD1G93A negative mice were used as the control group. At the age of 60 and 90 days, mice of the two EA groups received EA (2 Hz, 1 mA) stimulation of bilateral "Jiaji" (EX-B2) of L1-L2 and L5-L6 for 20 min, twice a week for 4 weeks,respectively. When being 60 days old, the mice in the model and control groups were subjected to the same binding as that in the two EA groups but without EA intervention. The tail suspension test was used to judge the onset time of disease and the survival period, and rotary rod fatigue test was used to evaluate the hind limb motor function. Nissl staining method was used to observe the content of Nissl bodies in the anterior horn of the lumbar spinal cord. Immunohistochemical staining was used to observe the expression of ionized calcium binding adaptor molecule-1 (Iba-1) in the anterior horn of the lumbar spinal cord, and Western blot was used to detect the relative expression of TLR4, NF-κB and tumor necrosis factor-α (TNF-α) in the lumbar spinal cord. The disease onset time apparently delayed in the 60 d EA group than in the model group (P<0.01). The survival time was apparently shorter in the model group than in the control group (P<0.01), and obviously prolonged in the 60 d EA and 90 d EA groups than in the model group (P<0.01). The rotatory rod time was obviously shorter in the model group than in the control group (P<0.05), and apparently longer in the 60 d EA group than in the model group and 90 d EA group (P<0.05). Compared with the control group, the model group had a decrease in the number of Nissl bodies in the anterior horn of the lumbar spinal cord (P<0.01), and an increase in the expression levels of Iba-1, TLR4, NF-κB and TNF-α in the lumbar spinal cord (P<0.01). In contrast to the model group, both 60 d EA and 90 d EA groups had an apparent increase in the number of Nissl bodies and a marked decrease in the expression levels of Iba-1, TLR4, NF-κB and TNF-α in the lumbar spinal cord (P<0.05, P<0.01). The therapeutic effects of 60 d EA group were evidently superior to those of 90 d EA group in delaying the onset time of disease, prolonging the survival time and rotatory rod time, increasing the number of Nissl bodies, and in down-regulating the expression of Iba-1, TLR4, NF-κB and TNF-α (P<0.05, P<0.01). The early intervention of EX-B2 EA is more effective in delaying the progression of ALS than post-onset intervention in ALS-SOD1G93A mice, which may be related to its functions in inhibiting the excessive activation of microglia, and down-regulating TLR4/NF-κB signaling.

Transcranial Direct Current Stimulation Modulates Working Memory Maintenance Processes in Healthy Individuals.

The effects of transcranial direct current stimulation (tDCS) at the pFC are often investigated using cognitive paradigms, particularly working memory tasks. However, the neural basis for the neuromodulatory cognitive effects of tDCS, including which subprocesses are affected by stimulation, is not completely understood. We investigated the effects of tDCS on working memory task-related spectral activity during and after tDCS to gain better insights into the neurophysiological changes associated with stimulation. We reanalyzed data from 100 healthy participants grouped by allocation to receive either sham (0 mA, 0.016 mA, and 0.034 mA) or active (1 mA or 2 mA) stimulation during a 3-back task. EEG data were used to analyze event-related spectral power in frequency bands associated with working memory performance. Frontal theta event-related synchronization (ERS) was significantly reduced post-tDCS in the active group. Participants receiving active tDCS had slower RTs following tDCS compared with sham, suggesting interference with practice effects associated with task repetition. Theta ERS was not significantly correlated with RTs or accuracy. tDCS reduced frontal theta ERS poststimulation, suggesting a selective disruption to working memory cognitive control and maintenance processes. These findings suggest that tDCS selectively affects specific subprocesses during working memory, which may explain heterogenous behavioral effects.

The potential applicability of facial nerve monitoring as a navigation tool in parotid gland surgery.

The aim of this study was to assess the relationship between the stimulation amplitude and the distance to the facial nerve. This study was designed as a prospective clinical study. A total of 20 patients (12 males, 8 females) were included. Partial superficial parotidectomy was performed in all patients with intraoperative facial monitoring. Measurements were made on the main trunk and major branches. Stimulation was started at 1 mA and incrementally increased to 2 and 3 mA's. The shortest distance creating a robust response (>100 mV) was recorded. At 1 mA, 2 mA and 3 mA stimulation intensity, the average distance between the tip of the stimulation probe and the main trunk was 2.20 ± 0.76 mm (range 1-3 mm), 3.80 ± 0.95 mm (range 2-5 mm), 4.80 ± 1.05 mm (range 3-7 mm) respectively. The stimulus intensity was inversely proportional in respect to the distance between the nerve and the tip of the stimulus probe (P < .00). The same relation was present in the facial nerve major branch measurements (P < .00). The proportional stimulation amplitude and distance to the facial nerve is thought to be a reliable auxillary method to assist the surgeon by facilitating the estimation of the distance to the facial nerve during extracapsular dissection and minimally invasive cases where the facial nerve isn't routinely dissected. Level 3.

Effects of electroacupuncture on sexual development and ovarian estrogen receptor β expression in female adolescent obese rats

To observe the effect of electroacupuncture on sexual development and ovarian estrogen receptor β(ER-β) expression in female adolescent obese rats induced by high-fat diet, so as to explore its underlying mechanisms of improving adolescent obesity. Female SD rats (age of 21 days) were randomly divided into control, model and acupuncture groups, with 6 rats in each group. The obese model was established by feeding high-fat diet for 6 weeks. Rats of the acupuncture group received electroacupuncture(2 Hz, 0.5-1.2 mA)stimulation at bilateral "Sanyinjiao"(SP6), "Fenglong"(ST40) and "Zusanli"(ST36) for 30 min, once a day for 14 days. The body mass and abdominal circumference of rats were measured before and after treatment. The contents of serum follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) were detected by ELISA. The number of corpus luteum and follicle were observed by HE staining. The expression levels of ER-β mRNA and protein in ovary were detected by fluorescence quantitative PCR and Western blot, respectively. Compared with the control group, the body mass and abdominal circumference, the contents of serum FSH and E2, and the expression levels of ER-β mRNA and protein in ovary were significantly increased (P<0.05)in the model group, while the number of mature follicles and corpus luteum increased significantly. Compared with the model group, the body mass and abdominal circumference, the contents of serum FSH and E2, and the expression levels of ER-β mRNA and protein in ovary were significantly decreased (P<0.05) in the acupuncture group, while the number of mature follicles and corpus luteum decreased significantly. Electroacupuncture can effectively improve the levels of sex hormone and the development of ovary, down-regulate the expression levels of ER-β mRNA and protein in ovary, so as to regulate the process of sexual development of female adolescent obese rats induced by high-fat diet.

TDCS augments decision-making efficiency in an intensity dependent manner: A training study

The application of transcranial direct current stimulation (tDCS) to the prefrontal cortex has the potential to improve performance more than cognitive training alone. Such stimulation-induced performance enhancements can generalize beyond trained tasks, leading to benefits for untrained tasks/processes. We have shown evidence that stimulation intensity has non-linear effects on augmenting cognitive training outcomes. However, it is currently unclear how stimulation intensity augments cognitive processing to impact training and transfer effects. Here, we applied decision-making modelling via the linear ballistic accumulator framework to understand what aspects of cognitive processes underlying speeded single-/dual-task decision-making performance change with tDCS intensity. One hundred and twenty-three participants were split into four groups: sham, 0.7 mA, 1.0 mA and 2.0 mA stimulation intensities. Participants completed four training sessions whilst tDCS was delivered. The 0.7 mA & 1.0 mA intensities provided the greatest benefit for performance (increased decision-making efficiency as measured by drift rates) on the trained task - more than sham or 2.0 mA stimulation. The latent decision components integrated both accuracy and reaction times to estimate performance more broadly. We see an inverted u-shaped function of stimulation intensity and cognitive performance in the trained-on task, where either no stimulation or too much stimulation is sub-optimal for performance. By contrast, 1.0 mA and 2.0 mA intensities led to increased drift rates in an untrained (transfer) single task. In sum, tDCS intensity non-linearly modulates cognitive processes related to decision-making efficiency.

Remotely monitored transcranial direct current stimulation in pediatric cerebral palsy: open label trial protocol

BackgroundPediatric applications of non-invasive brain stimulation using transcranial direct current stimulation (tDCS) have demonstrated its safety with few adverse events reported. Remotely monitored tDCS, as an adjuvant intervention to rehabilitation, may improve quality of life for children with cerebral palsy (CP) through motor function improvements, reduced treatment costs, and increased access to tDCS therapies. Our group previously evaluated the feasibility of a remotely monitored mock tDCS setup in which families and children successfully demonstrated the ability to follow tDCS instructional guidance.Methods and designHere, we designed a protocol to investigate the feasibility, safety, and tolerability of at-home active transcranial direct current stimulation in children with CP with synchronous supervision from laboratory investigators. Ten participants will be recruited to participate in the study for 5 consecutive days with the following sessions: tDCS setup practice on day 1, sham tDCS on day 2, and active tDCS on days 3-5. Sham stimulation will consist of an initial 30-second ramp up to 1.5 mA stimulation followed by a 30-second ramp down. Active stimulation will be delivered at 1.0 - 1.5 mA for 20 minutes and adjusted based on child tolerance. Feasibility will be evaluated via photographs of montage setup and the quality of stimulation delivery. Safety and tolerability will be assessed through an adverse events survey, the Box and Blocks Test (BBT) motor assessment, and a setup ease/comfort survey.DiscussionWe expect synchronous supervision of at-home teleneuromodulation to be tolerable and safe with increasing stimulation quality over repeated sessions when following a tDCS setup previously determined to be feasible. The findings will provide opportunity for larger clinical trials exploring efficacy and illuminate the potential of remotely monitored tDCS in combination with rehabilitation interventions as a means of pediatric neurorehabilitation. This will demonstrate the value of greater accessibility of non-invasive brain stimulation interventions and ultimately offer the potential to improve care and quality of life for children and families with CP.Trial RegistrationOctober 8, 2021(https://clinicaltrials.gov/ct2/show/NCT05071586)

A meta-analytical review of transcranial direct current stimulation parameters on upper limb motor learning in healthy older adults and people with Parkinson's disease.

Current literature lacks consolidated evidence for the impact of stimulation parameters on the effects oftranscranial direct current stimulation (tDCS) in enhancing upper limb motor learning. Hence, we aim to synthesise available methodologies and results to guide future research on the usage of tDCS on upper limb motor learning, specifically in older adults and Parkinson's disease (PD). Thirty-two studies (Healthy older adults, N=526, M=67.25, SD=4.30 years; PD, N=216, M=66.62, SD=6.25 years) were included in the meta-analysis. All included studies consisted of active and sham protocols. Random effect meta-analyses were conducted for (i)subjects (healthy older adults and PD); (ii) intensity (1.0, 1.5, 2mA); (iii) electrode montage (unilateral anodal, bilateral anodal, unilateral cathodal); (iv) stimulation site (cerebellum, frontal, motor, premotor, SMA, somatosensory); (v)protocol (online, offline). Significant tDCS effect on motor learning was reported for both populations, intensity 1.0 and 2.0mA, unilateral anodal and cathodal stimulation, stimulation site of the motor and premotor cortex, and both online and offline protocols. Regression showed no significant relationship between tDCS effects and density. The efficacy of tDCS is also not affected by the number of sessions. However, studies that reported only single session tDCS found significant negative association between duration with motor learning outcomes. Our findings suggest that different stimulation parameters enhanced upper limb motor learning in older adults and PD. Future research should combine tDCS with neuroimaging techniques to help with optimisation of the stimulation parameters, considering the type of task and population.

Effects of intervention combining transcranial direct current stimulation and foot core exercise on sensorimotor function in foot and static balance

ObjectiveThis study aimed to examine the effects of combining transcranial direct current stimulation (tDCS) and foot core exercise (FCE) on the sensorimotor function of the foot (i.e., toe flexor strength and passive ankle kinesthesia) and static balance.MethodsIn this double-blinded and randomized study, 30 participants were randomly assigned into two groups: tDCS combined with FCE and sham combined with FCE (i.e., control group). The participants received 2 mA stimulation for 20 min concurrently with FCE over 4 weeks (i.e., three sessions per week). After the first two groups completed the intervention, a reference group (FCE-only group) was included to further explore the placebo effects of sham by comparing it with the control group. Foot muscle strength, passive ankle kinesthesia, and static balance were assessed at baseline and after the intervention.ResultsCompared with the control group and baseline, tDCS combined with FCE could increase toe flexor strength (p < 0.001) and decrease the passive kinesthesia threshold of ankle eversion (p = 0.002). No significant differences in static balance were observed between tDCS + FCE and control groups. The linear regression models showed an association towards significance between the percent changes in metatarsophalangeal joint flexor strength and the anteroposterior average sway velocity of the center of gravity in one-leg standing with eyes closed following tDCS + FCE (r2 = 0.286; p = 0.057). The exploratory analysis also showed that compared with FCE alone, the sham stimulation did not induce any placebo effects during FCE.ConclusionParticipating in 4 weeks of intervention using tDCS in combination with FCE effectively enhances toe flexor strength and foot–ankle sensory function.

Electroacupuncture preconditioning improves pulmonary function via inhibiting inflammatory response and up-regulating expression of ACE2 and Ang (1-7) in lipopolysaccharide-induced acute lung injury rats

To observe the effect of electroacupuncture (EA) at "Zusanli"(ST36) pretreatment on lung functions, inflammatory response, and levels of angiotensin-converting enzyme 2 (ACE2) and angiotensin (1-7) ［Ang (1-7)］ in rats with sepsis-induced acute lung injury (ALI), so as to explore its mechanisms underlying improvement of ALI. Thirty male SD rats were randomly divided into normal, model and EA groups (n=10 in each group). The sepsis-related ALI model was established by intraperitoneal injection of lipopolysaccharide (LPS, 5 mg/kg). Rats of the EA group received EA (4 Hz/20 Hz, 1-3 mA) stimulation at bilateral ST36 for 30 min, once each day, for 7 days before modeling. The lung functions including forced vital capacity (FVC), forced expiratory volume at 0.1 second (FEV0.1) and FEV0.3 were detected using a respiratory function detector for small animals at 3 h after modeling. The bronchoalveolar lavage fluid (BALF) was collected for assaying the contents of Ang (1-7), tumor necrosis factor-α (TNF-α) and interleukin-1 β (IL-1β) using ELISA. The lung wet/dry weight (W/D) ratio, FEV0.1/FVC, and FEV0.3/FVC were calculated. The histopathological changes of lung tissues were displayed by hematoxylin-eosin (H.E.) staining. The expression of ACE2 and mitochondrial assembly receptor (MasR) mRNAs and proteins in the lung tissue was detected by fluorescence quantitative real-time PCR and Western blot, separately. Following modeling, the levels of FVC, FEV0.1, FEV0.3, ratio of FEV0.1/FVC and FEV0.3/FVC, content of Ang (1-7) in the BALF, and the expression levels of ACE2 and MasR mRNAs and proteins in the lung tissue were significantly decreased (P<0.01), while the level of W/D ratio and TNF-α and IL-1β contents in the BALF significantly increased (P<0.01) in the model group relevant to the normal group. In comparison with the model group, the levels of FVC, FEV0.1, FEV0.3, ratio of FEV0.1/FVC and FEV0.3/FVC, content of Ang (1-7) in the BALF, and expression levels of ACE2 and MasR mRNAs and proteins in the lung tissue were significantly increased (P<0.05, P<0.01), whereas the level of W/D ratio, and TNF-α and IL-1β contents in the BALF were significantly decreased (P<0.05, P<0.01) in the EA group. H.E. staining showed pulmonary interstitial edema and alveolar septum thickening with severe inflammatory cell infiltration in the model group, which was relatively milder in the EA group. EA preconditioning at ST36 can improve pulmonary function in sepsis-related ALI rats, which may be related to its effects in inhibiting inflammatory response and up-regulating ACE2 and MasR expression and Ang (1-7) content in the lung tissue.

Mapping and Monitoring of the Corticospinal Tract by Direct Brainstem Stimulation.

Direct stimulation and diffusion tensor imaging/tractography are established techniques that assist in complex surgery for lesions in the eloquent area of the central nervous system. To continuously map the corticospinal tract (CST) by direct stimulation during brainstem surgery and to explore the association between direct brainstem stimulation and the shortest distance from the stimulation point to the CST (DS-to-T). We prospectively enrolled 30 consecutive patients for microsurgical resection of lesions within or in proximity to the brainstem between January 2019 and August 2021. Direct stimulation with initially 2 mA was performed for mapping and monitoring the motor fiber tracts. To evaluate CST status and measure DS-to-T, postoperative diffusion tensor imaging/tractography was used. Preoperative and postoperative modified Ranking Scale and motor function were evaluated to assess the clinical outcome. Intraoperative direct brainstem stimulation was successfully performed in all patients with a total of 909 stimulation points. One patient experienced a temporary neurological deficit postoperatively. Mapping of the CST was achieved in 5 patients. DS-to-T was ≤4 mm when motor-evoked potential responses were positive under 2 mA stimulation and ≤2 mm under 1 mA. Overall sensitivity and specificity for this association were 84.7% and 100%, respectively. This study further supports the paradigm for continuous CST monitoring and mapping through direct brainstem stimulation. The relationship between stimulation intensity and DS-to-T in brainstem surgery could help surgeon's better estimate the safe edge intraoperatively.