Direct Current Electrical Stimulation Research Articles

Direct Current Electrical Stimulation Shifts THP-1-Derived Macrophage Polarization towards Pro-Regenerative M2 Phenotype.

A macrophage shift from the M1 to the M2 phenotype is relevant for promoting tissue repair and regeneration. In a previous in vivo study, we found that direct current (DC) electrical stimulation (EStim) increased the proportion of M2 macrophages in healing tissues and directed the balance of the injury response away from healing/scarring towards regeneration. These observations led us to hypothesize that DC EStim regulates macrophage polarization towards an M2 phenotype. THP-1-derived M0, M1 (IFN-γ and LPS), and M2 (IL-4 and IL-13) macrophages were exposed (or not: control group) to 100 mV/mm of DC EStim, 1 h/day for three days. Macrophage polarization was assessed through gene and surface marker expressions and cytokine secretion profiles. Following DC EStim treatment, M0 cells exhibited an upregulation of M2 marker genes IL10, CD163, and PPARG. In M1 cells, DC EStim upregulated the gene expressions of M2 markers IL10, TGM2, and CD206 and downregulated M1 marker gene CD86. EStim treatment also reduced the surface expression of CD86 and secretion of pro-inflammatory cytokines IL-1β and IL-6. Our results suggest that DC EStim differentially exerts pro-M2 effects depending on the macrophage phenotype: it upregulates typical M2 genes in M0 and M1 cells while inhibiting M1 marker CD86 at the nuclear and protein levels and the secretion of pro-inflammatory interleukins in M1 cells. Conversely, M2 cells appear to be less responsive to the EStim treatment employed in this study.

Towards optimized methodological parameters for maximizing the behavioral effects of transcranial direct current stimulation

IntroductionTranscranial direct current stimulation (tDCS) administers low-intensity direct current electrical stimulation to brain regions via electrodes arranged on the surface of the scalp. The core promise of tDCS is its ability to modulate brain activity and affect performance on diverse cognitive functions (affording causal inferences regarding regional brain activity and behavior), but the optimal methodological parameters for maximizing behavioral effects remain to be elucidated. Here we sought to examine the effects of 10 stimulation and experimental design factors across a series of five cognitive domains: motor performance, visual search, working memory, vigilance, and response inhibition. The objective was to identify a set of optimal parameter settings that consistently and reliably maximized the behavioral effects of tDCS within each cognitive domain.MethodsWe surveyed tDCS effects on these various cognitive functions in healthy young adults, ultimately resulting in 721 effects across 106 published reports. Hierarchical Bayesian meta-regression models were fit to characterize how (and to what extent) these design parameters differentially predict the likelihood of positive/negative behavioral outcomes.ResultsConsistent with many previous meta-analyses of tDCS effects, extensive variability was observed across tasks and measured outcomes. Consequently, most design parameters did not confer consistent advantages or disadvantages to behavioral effects—a domain-general model suggested an advantage to using within-subjects designs (versus between-subjects) and the tendency for cathodal stimulation (relative to anodal stimulation) to produce reduced behavioral effects, but these associations were scarcely-evident in domain-specific models.DiscussionThese findings highlight the urgent need for tDCS studies to more systematically probe the effects of these parameters on behavior to fulfill the promise of identifying causal links between brain function and cognition.

A 3D printable gelatin methacryloyl/chitosan hydrogel assembled with conductive PEDOT for neural tissue engineering

In neural tissue engineering, biomaterial scaffolds that have high conductivity and customized structures are crucial in promoting nerve regeneration. Poly(3,4-ethylenedioxythiophene) (PEDOT) has emerged as a promising conductive polymer with excellent chemical stability and biocompatibility. However, traditional three-dimensional (3D) printing of PEDOT-based conductive scaffolds faces challenges in limited printing resolution, poor solubility, and brittleness of conductive materials. Herein, digital light processing (DLP) printing was used to fabricate complex hydrogel structures using gelatin methacryloyl (GelMA) and chitosan (CS) while incorporating PEDOT nanoparticles through interfacial polymerization to create conducting pathways within a hydrogel structure. The integration of PEDOT significantly enhanced the electrical conductivity and mechanical properties of the GelMA/CS hydrogel while preserving printed details. The GelMA/CS-PEDOT hydrogel promoted cell proliferation and facilitated axon outgrowth of PC12 cells and Schwann cells during in vitro culture. Moreover, in vitro direct current electrical stimulation promoted axon elongation of PC12 cells cultured on a conductive substrate. In vivo studies used a conductive nerve conduit to repair a 10-mm rat sciatic nerve defect, validating the efficacy of GelMA/CS-PEDOT scaffold in peripheral nerve injury repair. These findings highlight the significant potential of conductive GelMA/CS-PEDOT hydrogel in the field of neural tissue engineering.

Efficacy and safety of non-invasive brain stimulation techniques for the treatment of nicotine addiction: A systematic review of randomized controlled trials

Non-Invasive Brain Stimulation (NIBS) techniques seem to be effective in treating tobacco use disorder. We aimed to analyze what kinds of protocols are used to treat nicotine addiction in term of cessation and/or reduction and to evaluate the long-term effects of NIBS techniques.We searched PubMed, Scopus, and Web of Science for papers published, with combinations of the following search terms: “<i>Non-invasive brain stimulation OR TMS OR transcranial magnetic stimulation OR tDCS OR transcranial direct current stimulation OR transcranial electrical stimulation OR TES AND Nicotine addiction</i>”.We conducted a preliminary search, which revealed papers on the topic. Articles were included in the review according to the following inclusion criteria: English language, publication in peer reviewed journals, articles about studies performed on non-invasive brain stimulations techniques, and RCT studies. Studies involving clinical populations with organic or psychiatric diseases were excluded. We found 280 articles. Of these, at the first screening and conducted by title and abstract, 63 studies were excluded after duplicates were removed (118). After the second screening conducted by full-text examination, 46 articles were excluded. Ten studies met the inclusion criteria and were included in the review.The clinical benefits of NIBS, including the fast onset and minor side effects, showed that this kind of treatment could be helpful in patients with a long history of smoking in terms of cessation and abstinence rates.

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.

Finite element analysis of electric field distribution during direct current stimulation of the spinal cord: Implications for device design.

Spinal cord injury (SCI) arises from damage to the spinal cord, often caused by trauma or disease. The resulting sensorimotor dysfunction is variable and dependent on the extent of the injury. Despite years of research, curative options for SCI remain limited. However, recent advancements in electric field stimulated axonal regrowth have shown promise for neuronal regeneration. One roadblock in the development of therapeutic treatments based on this is a lack of understanding of the exogenous electric field distribution in the injured tissue, and in particular, how this is influenced by electrode geometry and placement. To better understand this electric field, and provide a means by which it can be optimized, we have developed a finite element model of such spinal cord treatment. We investigate the impact of variations in electrode geometry, spinal cord size, and applied current magnitude as well as looking at several injury models in relation to clinically observed outcomes. Through this, we show that electrode shape has little effect on the induced electric field, that the placement of these electrodes has a noticeable influence on the field distribution, and that the magnitude of this field is governed by both the applied current and the spinal cord morphology. We also show that the injury modality influences the induced field distribution and that a stronger understanding of the injury will help decide treatment parameters. This work provides guidance in the design of electrodes for future clinical application in direct current electric field stimulation for axonal regeneration.

Repairing spinal cord injuries with electrical stimulation

Promising materials and technological advancements could facilitate practical application of direct current electrical stimulation to regenerate damaged tissue.

Generation of direct current electrical fields as regenerative therapy for spinal cord injury: A review.

Electrical stimulation (ES) shows promise as a therapy to promote recovery and regeneration after spinal cord injury. ES therapy establishes beneficial electric fields (EFs) and has been investigated in numerous studies, which date back nearly a century. In this review, we discuss the various engineering approaches available to generate regenerative EFs through direct current electrical stimulation and very low frequency electrical stimulation. We highlight the electrode-tissue interface, which is important for the appropriate choice of electrode material and stimulator circuitry. We discuss how to best estimate and control the generated field, which is an important measure for comparability of studies. Finally, we assess the methods used in these studies to measure functional recovery after the injury and treatment. This work reviews studies in the field of ES therapy with the goal of supporting decisions regarding best stimulation strategy and recovery assessment for future work.

A case series in individuals with multiple sclerosis using direct current electrical stimulation to inhibit spasticity and improve functional outcomes.

Multiple sclerosis (MS) has a high incidence of debilitating spasticity. Central Nervous System (CNS) intrafusal settings have an impact on spasticity level. Mechanoreceptors of the Peripheral Nervous System (PNS) communicate monosynaptically with the central nervous system (CNS). This case series assesses feasibility of multimodal treatment of individuals with MS using a direct current electrical stimulation (DC) to influence mechanoreceptors. Seven MS diagnosed participants with Expanded Disability Status Scale (EDSS) = 6.0-8.0 completed 18 visits over 6 weeks of using DC combined with neuromuscular reeducation. Design included pre-, post- outcome measures of EDSS, 12-item MS Walking Scale (MSWS-12), Range of Motion (ROM), Manual Muscle Testing (MMT), Modified Ashworth Test (MAT), Timed 25-Foot walk (T25WT), Timed Up and Go (TUG) and the Multiple Sclerosis Impact Scale-29 (MSIS-29). 125 out of a possible 126 visits were completed, demonstrating a high level of tolerance. Individual results included trends towards improvement in spasticity and agonists. This case series design of seven heterogenous subjects with MS is a low sample size for statistical analysis and should be considered a pilot. The study demonstrates a high level of feasibility and possible correlations to consider. Further research is warranted.

Addition of tDCS and TENS to an education and exercise program in subjects with knee osteoarthritis: A study protocol.

Knee osteoarthritis often leads to chronic pain that frequently becomes disabling.Osteoarthritis has been linked to maladaptive plasticity in the brain, which can contribute to chronic pain. Therapies including neuromodulation and peripheral electrical stimulation are used to counteract the maladaptive plasticity of the brain. To determine the efficacy of the addition of tDCS and TENS to an education and exercise program in reducing pain. Over a 2-week study period, 60 participants will complete an exercise and educational intervention. Eligible participants accepting to participate will be subsequently randomized into one of the three treatment groups: 1) Active Transcranial Direct Current Stimulation (tDCS) and active Transcutaneous Electrical Nerve Stimulation (TENS); 2) Active tDCS and sham TENS; 3) Sham tDCS and sham TENS. The primary outcome will be subjective pain intensity. quality of life, physical function, central sensitization, and pain adjuvants (uncertainty, catastrophizing kinesiophobia, adverse events). This clinical trial will provide data on the effect that the addition of tDCS and/or TENS to an education and exercise program may have to counteract maladaptive plastic changes and improve the benefits of exercises, and whether the combination of both neuromodulator techniques may have a higher magnitude of effect.

Transcranial direct current electrical stimulation in combination with aerobic exercise: A pilot study in post-COVID-19 systemic autoimmune rheumatic patients

Transcranial direct current electrical stimulation in combination with aerobic exercise: A pilot study in post-COVID-19 systemic autoimmune rheumatic patients

3D-Printed conductive polymeric scaffolds with direct current electrical stimulation for enhanced bone regeneration.

Various methods have been used to treat bone defects caused by genetic disorders, injury, or disease. Yet, there is still great need to develop alternative approaches to repair damaged bone tissue. Bones naturally exhibit piezoelectric potential, or the ability to convert mechanical stresses into electrical impulses. This phenomenon has been utilized clinically to enhance bone regeneration in conjunction with electrical stimulation (ES) therapies; however, oftentimes with critical-sized bone defects, the bioelectric potential at the site of injury is compromised, resulting in less desirable outcomes. In the present study, the potential of a 3D-printed conductive polymer blend to enhance bone formation through restoration of the bioelectrical microenvironment was evaluated. A commercially available 3D printer was used to create circular, thin-film scaffolds consisting of either polylactide (PLA) or a conductive PLA (CPLA) composite. Preosteoblast cells were seeded onto the scaffolds and subjected to direct current ES via a purpose-built cell culture chamber. It was found that CPLA scaffolds had no adverse effects on cell viability, proliferation or differentiation when compared with control scaffolds. The addition of ES, however, resulted in a significant increase in the expression of osteocalcin, a protein indicative of osteoblast maturation, after 14 days of culture. Furthermore, xylenol orange staining also showed the presence of increased mineralized calcium nodules in cultures undergoing stimulation. This study demonstrates the potential for low-cost, conductive scaffolding materials to support cell viability and enhance in vitro mineralization in conjunction with ES.

Electroactive Spinal Instrumentation for Targeted Osteogenesis and Spine Fusion: A Computational Study.

Direct current electrical stimulation may serve as a promising nonpharmacological adjunct promoting osteogenesis and fusion. The aim of this study was to evaluate the utility of electroactive spine instrumentation in the focal delivery of therapeutic electrical stimulation to enhance lumbar bone formation and interbody fusion. A finite element model of adult human lumbar spine (L4-L5) instrumented with single-level electroactive pedicle screws was simulated. Direct current electrical stimulation was routed through anodized electroactive pedicle screws to target regions of fusion. The electrical fields generated by electroactive pedicle screws were evaluated in various tissue compartments including isotropic tissue volumes, cortical, and trabecular bone. Electrical field distributions at various stimulation amplitudes (20-100 µA) and pedicle screw anodization patterns were analyzed in target regions of fusion (eg, intervertebral disc space, vertebral body, and pedicles). Electrical stimulation with electroactive pedicle screws at various stimulation amplitudes and anodization patterns enabled modulation of spatial distribution and intensity of electric fields within the target regions of lumbar spine. Anodized screws (50%) vs unanodized screws (0%) induced high-amplitude electric fields within the intervertebral disc space and vertebral body but negligible electric fields in spinal canal. Direct current electrical stimulation via anodized screws induced electrical fields, at therapeutic threshold of >1 mV/cm, sufficient for osteoinduction within the target interbody region. Selective anodization of electroactive pedicle screws may enable focal delivery of therapeutic electrical stimulation in the target regions in human lumbar spine. This study warrants preclinical and clinical testing of integrated electroactive system in inducing target lumbar fusion in vivo. The findings of this study provide a foundation for clinically investigating electroactive intrumentation to enhance spine fusion.

Effect of direct current electrical stimulation on osteogenic differentiation and calcium influx

Effect of direct current electrical stimulation on osteogenic differentiation and calcium influx

Bioelectronic microfluidic wound healing: a platform for investigating direct current stimulation of injured cell collectives.

Upon cutaneous injury, the human body naturally forms an electric field (EF) that acts as a guidance cue for relevant cellular and tissue repair and reorganization. However, the direct current (DC) flow imparted by this EF can be impacted by a variety of diseases. This work delves into the impact of DC stimulation on both healthy and diabetic in vitro wound healing models of human keratinocytes, the most prevalent cell type of the skin. The culmination of non-metal electrode materials and prudent microfluidic design allowed us to create a compact bioelectronic platform to study the effects of different sustained (12 hours galvanostatic DC) EF configurations on wound closure dynamics. Specifically, we compared if electrotactically closing a wound's gap from one wound edge (i.e., uni-directional EF) is as effective as compared to alternatingly polarizing both the wound's edges (i.e., pseudo-converging EF) as both of these spatial stimulation strategies are fundamental to the eventual translational electrode design and strategy. We found that uni-directional electric guidance cues were superior in group keratinocyte healing dynamics by enhancing the wound closure rate nearly three-fold for both healthy and diabetic-like keratinocyte collectives, compared to their non-stimulated respective controls. The motility-inhibited and diabetic-like keratinocytes regained wound closure rates with uni-directional electrical stimulation (increase from 1.0 to 2.8% h-1) comparable to their healthy non-stimulated keratinocyte counterparts (3.5% h-1). Our results bring hope that electrical stimulation delivered in a controlled manner can be a viable pathway to accelerate wound repair, and also by providing a baseline for other researchers trying to find an optimal electrode blueprint for in vivo DC stimulation.

Effects of transcranial direct current stimulation in dysphagic patients

To determine the effects and effectiveness of transcranial direct current electrical stimulation in patients with complaints of gluttony. RESEARCH STRATEGIES: This is a systematic review and meta-analysis, qualitative and quantitative article. PubMed, ScienceDirect, and BVS Regional Portal were used as databases. They were only clinically controlled and/or randomized clinical trials from 2011 to 2020. SELECTION CRITERIA: Descriptors were used in a combined way: [(dysphagia AND tDCS) OR (dysphagia AND "transcranial stimulation") OR (tDCS AND swallowing)]. DATA ANALYSIS: Meta-analysis was performed using R statistical software version 4.0.2. When grouping effect sizes in Meta-analysis, two approaches were used: the Fixed Effects Model and the Random Effects model. RESULTS: After applying the selection criteria, 5 articles met the requirements for qualitative analysis and 3 for quantitative analysis (meta-analysis). The studies included had a mean of 5.2 years ± 2.38 years of publication and population obtained from patients with changes in gluttony after stroke. A stimulation modality chosen for intervention was the anodic type (n = 5; 100%), prioritizing a representation of the pharynx in the cortex engine, ranging from 4 to 30 combined tDCS. CONCLUSION: There was clinical improvement in the patients, with therapeutic advances being important in the medium term. It is noteworthy that the importance of conducting clinical studies with a greater number of participants is to carry out possible greater sedimentation of the technique in rehabilitating motor, sensory, and/or mixed swallowing genesis disorders.

DC electrical stimulation enhances proliferation and differentiation on N2a and MC3T3 cell lines

BackgroundElectrical stimulation is a novel tool to promote the differentiation and proliferation of precursor cells. In this work we have studied the effects of direct current (DC) electrical stimulation on neuroblastoma (N2a) and osteoblast (MC3T3) cell lines as a model for nervous and bone tissue regeneration, respectively. We have developed the electronics and encapsulation of a proposed stimulation system and designed a setup and protocol to stimulate cell cultures.MethodsCell cultures were subjected to several assays to assess the effects of electrical stimulation on them. N2a cells were analyzed using microscope images and an inmunofluorescence assay, differentiated cells were counted and neurites were measured. MC3T3 cells were subjected to an AlamarBlue assay for viability, ALP activity was measured, and a real time PCR was carried out.ResultsOur results show that electrically stimulated cells had more tendency to differentiate in both cell lines when compared to non-stimulated cultures, paired with a promotion of neurite growth and polarization in N2a cells and an increase in proliferation in MC3T3 cell line.ConclusionsThese results prove the effectiveness of electrical stimulation as a tool for tissue engineering and regenerative medicine, both for neural and bone injuries. Bone progenitor cells submitted to electrical stimulation have a higher tendency to differentiate and proliferate, filling the gaps present in injuries. On the other hand, neuronal progenitor cells differentiate, and their neurites can be polarized to follow the electric field applied.

Rehabilitation of patients with post-stroke aphasia using transcranial direct current electrical stimulation (tDCS)

BACKGROUND: Rehabilitation of patients with post-stroke aphasia is an important medical and social goal. The use of traditional methods of rehabilitation is often not effective enough, which forces us to look for new methods aimed at restoring lost functions.
 AIM: The aim of this study is to determine the effectiveness of non-invasive brain stimulation using transcranial direct electric current stimulation (tDCS) in patients with post-stroke aphasia.
 MATERIALS AND METHODS: 28 patients with motor post-stroke aphasia were examined according to the method of L.S. Tsvetkova with co-authors. All patients received a traditional rehabilitation complex: psychological and correctional classes with a speech therapist-aphasiologist; neurometabolic therapy. 14 patients (Group I) additionally had transcranial direct electric current stimulation; 14 patients had placebo transcranial direct electric current stimulation.
 RESULTS: All patients with post-stroke aphasia showed an improvement in expressive and impressive speech, however, in patients who had true transcranial direct electric current stimulation, the improvement in expressive and impressive speech was higher than in patients who had placebo transcranial direct electric current stimulation. There were no complications from the use of transcranial direct electric current stimulation.
 CONCLUSION: Based on the results of the study, it can be concluded that it is expedient to include the non-invasive transcranial direct electric current stimulation method in the rehabilitation of patients with post-stroke aphasia.

The Nonspecific Positive Actions of Direct Current Transcranial Electrical Stimulation on Novel Word Acquisition

The Nonspecific Positive Actions of Direct Current Transcranial Electrical Stimulation on Novel Word Acquisition

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

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