Direct Current Stimulation Research Articles

Transcranial Direct-current Stimulation of the Dorsolateral Prefrontal Cortex Modulates Voluntary Task-order Coordination in Dual-task Situations.

Dual tasks (DTs) require additional control processes that temporally coordinate the processing of the two component tasks. Previous studies employing imaging as well as noninvasive stimulation techniques have demonstrated that the dorsolateral prefrontal cortex (dlPFC) is causally involved in these task-order coordination processes. However, in these studies, participants were instructed to match their processing order to an externally provided and mandatory order criterion during DT processing. Hence, it is still unknown whether the dlPFC is also recruited for rather voluntary order control processes, which are required in situations that allow for intentional and internally generated order choices. To address this issue, in two experiments, we applied anodal (Experiment 1) and cathodal (Experiment 2) transcranial direct-current stimulation during a random-order DT in which participants could freely decide about their order of task processing. In our results, we found facilitatory and inhibitory effects on voluntary task-order coordination because of anodal and cathodal transcranial direct-current stimulation, respectively. This was indicated by shorter RTs when participants intentionally switched the task order relative to the preceding trial during anodal as well as a reduced tendency to switch the task order relative to the preceding trial during cathodal stimulation compared with the sham stimulation. Overall, these findings indicate that the dlPFC is also causally involved in voluntary task-order coordination processes. In particular, we argue that the dlPFC is recruited for intentionally updating and implementing task-order information that is necessary for scheduling the processing of two temporally overlapping tasks.

Machine learning-optimized non-invasive brain stimulation and treatment response classification for major depression

Background/ObjectivesTranscranial direct current stimulation (tDCS) is a non-invasive brain stimulation intervention that shows promise as a potential treatment for depression. However, the clinical efficacy of tDCS varies, possibly due to individual differences in head anatomy affecting tDCS dosage. While functional changes in brain activity are more commonly reported in major depressive disorder (MDD), some studies suggest that subtle macroscopic structural differences, such as cortical thickness or brain volume reductions, may occur in MDD and could influence tDCS electric field (E-field) distributions. Therefore, accounting for individual anatomical differences may provide a pathway to optimize functional gains in MDD by formulating personalized tDCS dosage.MethodsTo address the dosing variability of tDCS, we examined a subsample of sixteen active-tDCS participants’ data from the larger ELECT clinical trial (NCT01894815). With this dataset, individualized neuroimaging-derived computational models of tDCS current were generated for (1) classifying treatment response, (2) elucidating essential stimulation features associated with treatment response, and (3) computing a personalized dose of tDCS to maximize the likelihood of treatment response in MDD.ResultsIn the ELECT trial, tDCS was superior to placebo (3.2 points [95% CI, 0.7 to 5.5; P = 0.01]). Our algorithm achieved over 90% overall accuracy in classifying treatment responders from the active-tDCS group (AUC = 0.90, F1 = 0.92, MCC = 0.79). Computed precision doses also achieved an average response likelihood of 99.981% and decreased dosing variability by 91.9%.ConclusionThese findings support our previously developed precision-dosing method for a new application in psychiatry by optimizing the statistical likelihood of tDCS treatment response in MDD.

Enhancing CAR-T cell therapy against solid tumor by drug-free triboelectric immunotherapy

Chimeric antigen receptor (CAR) T cell therapy is a highly effective immunotherapy for hematological tumors, but its efficacy against most solid tumors remains challenging. Herein, a novel synergistic combination therapy of drug-free triboelectric immunotherapy and CAR-T cell therapy against solid tumor was proposed. A triboelectric nanogenerator (TENG) that can generate pulsed direct-current by coupling triboelectrification effect and electrostatic breakdown effect was fabricated. The TENG can generate up to 30 pulse direct-current peaks with peak current output ≈35 μA in a single sliding to power the triboelectric immunotherapy. The pulsed direct-current stimulation induced immunogenic cell death of tumor cells (survival rate of 35.9 %), which promoted dendritic cells maturation, accelerated the process of antigen presentation to CAR-T cells and enhanced the systemic adaptive immune response. Furthermore, triboelectric immunotherapy promoted M1-like macrophage polarization, reduced regulatory T cells differentiation and reprogrammed the tumor immunosuppressive microenvironment, which ultimately enhanced the efficacy of CAR-T cells to eradicate nearly 60 % of NALM6 solid tumor mass. Notably, considering that triboelectric immunotherapy is a safe and effective drug-free antitumor strategy, the combined therapy did not increase the burden of double-medication on patients.

Transcranial Direct-Current Stimulation Over the Primary Motor Cortex and Cerebellum Improves Balance and Shooting Accuracy in Elite Ice Hockey Players.

To investigate the effects of transcranial direct-current stimulation (tDCS) applied over the primary motor cortex (M1) and cerebellum on balance control and shooting accuracy in elite ice hockey players. Twenty-one elite ice hockey players underwent anodal tDCS over theM1 (a-tDCSM1), anodal tDCS over the cerebellum (a-tDCSCB), concurrent dual-site anodal tDCS over the M1 and the cerebellum (a-tDCSM1+CB), and sham stimulation (tDCSSHAM). Before and after receiving tDCS (2mA for 15min), participants completed an ice hockey shooting-accuracy test, Pro-Kin balance test (includes stance test and proprioceptive assessment), and Y-balance test in randomized order. For static balance performance, the ellipse area in the 2-legged stance with eyes open and the 1-legged stance with the dominant leg significantly improved following a-tDCSM1, a-tDCSCB, and concurrent dual-site a-tDCSM1+CB, compared with tDCSSHAM (all P < .05, Cohen d = 0.64-1.06). In dynamic balance performance, the average trace error of the proprioceptive assessment and the composite score of the Y-balance test with the dominant leg significantly improved following a-tDCSM1 and concurrent dual-site a-tDCSM1+CB (all P < .05, Cohen d = 0.77-1.00). For the ice hockey shooting-accuracy test, shooting-accuracy while standing on the unstable platform significantly increased following a-tDCSM1 (P = .010, Cohen d = 0.81) and a-tDCSCB (P = .010, Cohen d = 0.92) compared with tDCSSHAM. tDCS could potentially be a valuable tool in enhancing static and dynamic balance and shooting accuracy on unstable platforms in elite ice hockey players.

Influence of bilateral transcranial direct-current stimulation on muscle strength and respiratory endurance: Randomized, placebo-controlled, double-blind trial protocol

Transcranial direct current stimulation (tDCS) has become established as an effective therapeutic approach, employed to modulate cortical excitability in various conditions. Nonetheless, few studies have assessed the use of tDCS in improving respiratory performance both in healthy and in subjects with respiratory disfunction. This randomized double-blind placebo-controlled trial evaluated the outcomes of lung function, strength of inspiratory muscles, general strength after intervention with bilateral tDCS both in young and elderly female subjects. Eighty subjects were randomized into four groups divided by age (40 young and 40 elderly) and intervention vs. placebo. After a basal (day 1) evaluation all subjects performed two evaluation/intervention rounds with 48 to 72 h interval. Lung function evaluated with spirometry evaluation with Forced vital capacity (FVC), Forced Expiratory Volume in 1 S (FEV1), FEV1/FVC Ratio, Maximal Voluntary Ventilation (MVV); Dynamic Inspiratory muscle strength evaluated with Powerbreathe and general strength with dynamometer. This study intends to understand the behavior of respiratory muscle strength and endurance after intervention with bilateral cathodal tDCS over the primary motor cortex in healthy young and elderly subjects, as a bridge for larger studies both in healthy and rehabilitation setting.

Visual long-term memory is not made more precise with medial-frontal direct-current stimulation

ABSTRACT Previous research suggests that applying anodal transcranial direct-current stimulation (tDCS) to the medial-frontal cortex can improve how quickly subjects learn to make simple discriminations (i.e., red from blue). Here, we tested the idea that this enhanced task learning is attributable to superior encoding of relevant information into visual long-term memory. Thirty subjects completed an anodal stimulation session and a sham session, with order counterbalanced across subjects, before performing recognition-memory tasks using pictures of real-world objects and visually presented words or nonwords. These tasks allowed us to detect potential memory differences across types of memoranda. Contrary to the hypothesis that the medial-frontal cortex helps control encoding fidelity, we found that anodal tDCS delivered over this brain region did not significantly improve subjects’ memory for visual stimuli, regardless of stimulus type. Our findings show no evidence that targeting medial-frontal cortex with tDCS changes the fidelity of our visual long-term memories.

Effects of Transcranial Direct-Current Stimulation on Rumination and Self-inhibition in Patients with Panic Disorder

Background: Panic disorder causes patients to cease their daily activities and avoid social interactions. Appropriate treatment helps these patients manage their worries, rumination, and self-inhibition, allowing them to return to normalcy. Objectives: This research aims to investigate the effectiveness of transcranial direct-current stimulation (tDCS) on rumination and self-inhibition in patients with panic disorder. Methods: This quasi-experimental research used a pretest-posttest control group design. The statistical population comprised patients with panic disorder aged 18 - 45 years who visited psychotherapy centers in Ahvaz, Iran, in 2023. Convenience sampling was employed to select 40 eligible participants, who were then randomly assigned to an experimental group (n = 20) and a control group (n = 20). Participants completed rumination and self-inhibition questionnaires at the pretest and posttest stages. The experimental group received ten 20-minute sessions of tDCS. Data were collected using the Ruminative Response Scale (RRS) and Self-Restraint Scale (SRS). Analysis of covariance (ANCOVA) was used for data analysis. Results: The results indicated that tDCS improved rumination and self-inhibition in the posttest stage, demonstrating the treatment's effectiveness (P &lt; 0.001). Conclusions: Transcranial direct-current stimulation can alleviate rumination and improve self-inhibition in patients with panic disorder. It is recommended that tDCS be used as a complementary treatment for these patients.

Direct current stimulation as a non-invasive therapeutic alternative for treating autonomic or non-autonomic neurological disorders affecting breathing.

Direct current stimulation (DCS) is a non-invasive approach to stimulate the nervous system that is now considered a powerful tool for treating neurological diseases such as those affecting cognitive or locomotor functions. DCS, as applied clinically today, is an approach built on early uses in antiquity and knowledge gained over time. Its current usemakes use of specific devices and takes into account knowledge of the mechanisms by which this approach modulates functioning of the nervous system at the cellular level. Over the last 20years, although there are few studies, it has been shown that DCS can also modulate the breathing autonomic function. In this narrative review, after briefly providing the historical perspective and describing the principles and the main cellular and molecular effects, we summarize the currently available data regarding the modulation of ventilation, and propose that DCS could be used to treat autonomic or non-autonomic neurological disorders affecting breathing.

Somatodendritic orientation determines tDCS-induced neuromodulation of Purkinje cell activity in awake mice.

Transcranial direct-current stimulation (tDCS) of the cerebellum is a promising non-invasive neuromodulatory technique being proposed for the treatment of neurological and neuropsychiatric disorders. However, there is a lack of knowledge about how externally applied currents affect neuronal spiking activity in cerebellar circuits in vivo. We investigated how Cb-tDCS affects the firing rate of Purkinje cells (PC) and non-PC in the mouse cerebellar cortex to understand the underlying mechanisms behind the polarity-dependent modulation of neuronal activity induced by tDCS. Mice (n = 9) were prepared for the chronic recording of LFPs to assess the actual electric field gradient imposed by Cb-tDCS in our experimental design. Single-neuron extracellular recording of PCs in awake (n = 24) and anesthetized (n = 27) mice was combined with juxtacellular recordings and subsequent staining of PC with neurobiotin under anesthesia (n = 8) to correlate their neuronal orientation with their response to Cb-tDCS. Finally, a high-density Neuropixels recording system was used to demonstrate the relevance of neuronal orientation during the application of Cb-tDCS in awake mice (n = 6) In this study, we observe that Cb-tDCS induces a heterogeneous polarity-dependent modulation of the firing rate of Purkinje cells (PC) and non-PC in the mouse cerebellar cortex. We demonstrate that the apparently heterogeneous effects of tDCS on PC activity can be explained by taking into account the somatodendritic orientation relative to the electric field. Our findings highlight the need to consider neuronal orientation and morphology to improve tDCS computational models, enhance stimulation protocol reliability, and optimize effects in both basic and clinical applications.

Neuromodulatory effects of parietal high-definition transcranial direct-current stimulation on network-level activity serving fluid intelligence.

Fluid intelligence (Gf) involves rational thinking skills and requires the integration of information from different cortical regions to resolve novel complex problems. The effects of non-invasive brain stimulation on Gf have been studied in attempts to improve Gf, but such studies are rare and the few existing have reached conflicting conclusions. The parieto-frontal integration theory of intelligence (P-FIT) postulates that the parietal and frontal lobes play a critical role in Gf. To investigate the suggested role of parietal cortices, we applied high-definition transcranial direct current stimulation (HD-tDCS) to the left and right parietal cortices of 39 healthy adults (age 19-33years) for 20min in three separate sessions (left active, right active and sham). After completing the stimulation session, the participants completed a logical reasoning task based on Raven's Progressive Matrices during magnetoencephalography. Significant neural responses at the sensor level across all stimulation conditions were imaged using a beamformer. Whole-brain, spectrally constrained functional connectivity was then computed to examine the network-level activity. Behaviourally, we found that participants were significantly more accurate following left compared to right parietal stimulation. Regarding neural findings, we found significant HD-tDCS montage-related effects in brain networks thought to be critical for P-FIT, including parieto-occipital, fronto-occipital, fronto-parietal and occipito-cerebellar connectivity during task performance. In conclusion, our findings showed that left parietal stimulation improved abstract reasoning abilities relative to right parietal stimulation and support both P-FIT and the neural efficiency hypothesis. KEY POINTS: Abstract reasoning is a critical component of fluid intelligence and is known to be served by multispectral oscillatory activity in the fronto-parietal cortices. Recent studies have aimed to improve abstract reasoning abilities and fluid intelligence overall through behavioural training, but the results have been mixed. High-definition transcranial direct-current stimulation (HD-tDCS) applied to the parietal cortices modulated task performance and neural oscillations during abstract reasoning. Left parietal stimulation resulted in increased accuracy and decreased functional connectivity between occipital regions and frontal, parietal, and cerebellar regions. Future studies should investigate whether HD-tDCS alters abstract reasoning abilities in those who exhibit declines in performance, such as healthy ageing populations.

Effect of a Neuromodulation Protocol Associated With Sports Training on the Precision Sports Performance of a Wheelchair Basketball Para-Athlete: A Case Study.

To investigate whether transcranial direct-current stimulation (tDCS) optimizes the performance of a wheelchair basketball player on precision tasks. A right-handed wheelchair basketball player (1.5 points functional class) with myelomeningocele (low lumbar level) participated in this case study. The tDCS neuromodulation protocol was applied throughout 10 interventions of 20 minutes with a current intensity of 2mA, simultaneously with sport-specific training, 3times a week for 4weeks. Anodic stimulation was performed on the right cerebellar hemisphere (CB2) and cathodic stimulation in the left dorsolateral prefrontal cortex. A control participant was submitted to a sham-tDCS stimulation protocol for the same period. Functional performance was assessed before the intervention and after the 5th and 10th interventions using "pass accuracy," "free-throw shooting," and "spot shot" tests. Outcome measures were compared using percentage differences between preintervention, intermediate intervention, and postintervention values. There was a gradual increase in the athlete's total and average scores in all tests performed, with an overall improvement of 78% between the baseline and final assessments, while the control participant had an overall improvement of 6.5%. The tDCS protocol was effective in improving performance in precision activities in a wheelchair basketball player.

Effects of transcranial direct current stimulation and sensorimotor training in anterior cruciate ligament patients: a sham-controlled pilot study.

Studies showed changes in the central nervous system in patients who sustained an anterior cruciate ligament tear. There is a lack of evidence regarding the effectiveness of transcranial direct-current stimulation in such patients. A sham-controlled randomised study. One group of patients (n = 6) underwent 6 weeks of sensorimotor training after an anterior cruciate ligament tear during transcranial direct-current stimulation. The stimulation consisted of 20 minutes (3 sessions/week; 2 weeks) of 2 mA anodal transcranial direct-current stimulation over the primary motor and premotor cortex. The second group (n = 6) received sham stimulation with 6 weeks of sensorimotor training. Centre of pressure deviations in the medio-lateral and anterior-posterior direction and centre of pressure velocity were measured. The results demonstrated a significant effect of sensorimotor training on the centre of pressure in medio-lateral and anterior-posterior direction (p=0.025) (p=0.03) in the leg in which an anterior cruciate ligament tear occurred. The type of training did not affect the results. Post-hoc tests showed no significant effect of training in the subgroups (p≥0.115). Sensorimotor training led to a decrease in sway of the centre of pressure in patients who sustained an anterior cruciate ligament tear, but the addition of anodal transcranial direct-current stimulation placed over the primary motor cortex did not potentiate the adaptive responses of the sensorimotor training.

Site Dependency of Anodal Transcranial Direct-Current Stimulation on Reaction Time and Transfer of Learning during a Sequential Visual Isometric Pinch Task.

Considering the advantages of brain stimulation techniques in detecting the role of different areas of the brain in human sensorimotor behaviors, we used anodal transcranial direct-current stimulation (a-tDCS) over three different brain sites of the frontoparietal cortex (FPC) in healthy participants to elucidate the role of these three brain areas of the FPC on reaction time (RT) during a sequential visual isometric pinch task (SVIPT). We also aimed to assess if the stimulation of these cortical sites affects the transfer of learning during SVIPT. A total of 48 right-handed healthy participants were randomly assigned to one of the four a-tDCS groups: (1) left primary motor cortex (M1), (2) left dorsolateral prefrontal cortex (DLPFC), (3) left posterior parietal cortex (PPC), and (4) sham. A-tDCS (0.3 mA, 20 min) was applied concurrently with the SVIPT, in which the participants precisely controlled their forces to reach seven different target forces from 10 to 40% of the maximum voluntary contraction (MVC) presented on a computer screen with the right dominant hand. Four test blocks were randomly performed at the baseline and 15 min after the intervention, including sequence and random blocks with either hand. Our results showed significant elongations in the ratio of RTs between the M1 and sham groups in the sequence blocks of both the right-trained and left-untrained hands. No significant differences were found between the DLPFC and sham groups and the PPC and sham groups in RT measurements within the SVIPT. Our findings suggest that RT improvement within implicit learning of an SVIPT is not mediated by single-session a-tDCS over M1, DLPFC, or PPC. Further research is needed to understand the optimal characteristics of tDCS and stimulation sites to modulate reaction time in a precision control task such as an SVIPT.

Effectiveness of Transcranial Direct-Current Stimulation on Impulsivity and Anxiety in Patients with Paranoid Personality Disorder

Background: Individuals with paranoid personality disorder (PPD) usually suffer from impulsive behavior and anxiety and constantly imagine others trying to humiliate, harm, or threaten them. This disorder causes mistrust towards others and may interfere with a person's ability to form close relationships. Objectives: The present study aimed to investigate the effects of transcranial direct-current stimulation (tDCS) on impulsivity and anxiety in patients with PPD. Methods: This quasi-experimental research adopted a pretest-posttest control group design. The statistical population included all patients aged 30 – 50 years with PPD referred to psychological and psychiatric clinics and hospitals in Yazd, (Iran), in 2022. Convenience sampling was employed to select 30 individuals with PPD. The participants were randomly assigned to an experimental group (n = 15) and a control (n = 15) group using a table of random numbers. The participants completed impulsivity and anxiety questionnaires during the pretest and posttest stages. The experimental group received ten 20-minute sessions of tDCS. The collected data were analyzed using SPSS v25.0. Results: The participants included 30 men and women with PPD with an average age of 41.23 ± 8.40 years. In the posttest, the mean ± SD of impulsivity for tDCS and control groups were 54.67 ± 4.03 and 93.93 ± 3.67, respectively. Moreover, the mean ± SD of anxiety in tDCS and control groups in the posttest were 16.40 ± 2.79 and 42.39 ± 2.99, respectively. The results indicated that tDCS significantly improved impulsivity and reduced anxiety at the posttest stage (P &lt; 0.001). Conclusions: Transcranial direct-current stimulation can alleviate impulsivity and anxiety in patients with PPD. Therefore, therapists can implement the tDCS method as a complementary therapy to improve impulsivity and anxiety in patients with PPD.

Direct Current Stimulation over the Primary Motor Cortex, Cerebellum, and Spinal Cord to Modulate Balance Performance: A Randomized Placebo-Controlled Trial.

Existing applications of non-invasive brain stimulation in the modulation of balance ability are focused on the primary motor cortex (M1). It is conceivable that other brain and spinal cord areas may be comparable or more promising targets in this regard. This study compares transcranial direct current stimulation (tDCS) over (i) the M1, (ii) the cerebellum, and (iii) trans-spinal direct current stimulation (tsDCS) in the modulation of balance ability. Forty-two sports students were randomized in this placebo-controlled study. Twenty minutes of anodal 1.5 mA t/tsDCS over (i) the M1, (ii) the cerebellum, and (iii) the spinal cord, as well as (iv) sham tDCS were applied to each subject. The Y Balance Test, Single Leg Landing Test, and Single Leg Squat Test were performed prior to and after each intervention. The Y Balance Test showed significant improvement after real stimulation of each region compared to sham stimulation. While tsDCS supported the balance ability of both legs, M1 and cerebellar tDCS supported right leg stand only. No significant differences were found in the Single Leg Landing Test and the Single Leg Squat Test. Our data encourage the application of DCS over the cerebellum and spinal cord (in addition to the M1 region) in supporting balance control. Future research should investigate and compare the effects of different stimulation protocols (anodal or cathodal direct current stimulation (DCS), alternating current stimulation (ACS), high-definition DCS/ACS, closed-loop ACS) over these regions in healthy people and examine the potential of these approaches in the neurorehabilitation.

Transcranial Direct Current Stimulation (tDCS) as a Therapeutic Tool for Chronic Insomnia

&#x0D; &#x0D; &#x0D; &#x0D; Background and Objective: Insomnia is the most common sleep problem which is associated with cortical over- excitation. Transcranial direct-current stimulation (tDCS) potentially modifies insomnia-related cortical state. There- fore, we tested the hypothesis that insomnia severity can be modulated by tDCS.&#x0D; Materials and Methods: The current study was conducted with a pretest-posttest design and a control group. A total of 32 women with insomnia were randomly categorized into an intervention group (active stimulation) and a control group (sham stimulation). In the intervention group, tDCS ‎was used with an intensity of 2mA for 20 to 30 minutes during 12 sessions (3 times a week). Anodal stimulation was performed‎on the left primary motor cortex (M1) and cathodal stimulation was performed‎on the right dorsal lateral prefrontal cortex (DLPFC). The control group received sham stim- ulation for 20 to 30 minutes during 12 sessions (3 times a week). All participants were evaluated before and after the intervention using the Insomnia Severity Index (ISI) and Positive Affect and Negative Affect Schedule (PANAS).&#x0D; Results: The results of univariate analysis of covariance (ANCOVA) and multivariate analysis of covariance (MANCOVA) showed a significant difference between the tDCS group and the sham group in terms of reduction in the severity of insomnia. We also observed that positive affect increased and negative affect decreased following insomnia treatment (P ≤ 0.005).&#x0D; Conclusion: The results of our study indicated that performing our designed tDCS protocol for treating insomnia can be effective in treating insomnia and improving positive and negative affect.&#x0D; &#x0D; &#x0D; &#x0D;

Effect of Intensified Transcranial Direct-current Stimulation Targeting Bilateral Dorsolateral Prefrontal Cortex on Craving Reduction in Patients with Opioid (Heroin) Use Disorder.

: This study aimed to analyze the effect of the intensified transcranial direct-current stimulation (tDCS) targeting bilateral dorsolateral prefrontal cortex (DLPFC) on craving reduction in patients with opioid use disorder. : This quasi-experimental study was conducted on 30 individuals who participated voluntarily at Baharan Camp of Shahid Mahalati. The participants had already completed the detoxification phase and stayed at the camp to resolve their craving and gain occupational skills to reintegrate into the community. The participants were selected using convenience and purposive sampling methods and were then assigned to an experimental group (n = 15) and a control group (n = 15). The experimental group received ten 20-minute tDCS sessions twice a day for 5 consecutive days. There was a 20-minute break between the two stimulations. The DLPFC was stimulated with a current intensity of 2 mA (anode: F3 and cathode: F4). The control group received a sham stimulation. Both groups completed Franken's Desires for Drug Questionnaire at baseline and after the stimulation sessions. Additionally, they completed the questionnaires once again three months after the end of the treatment to assess treatment retention. : At the posttest stage, the intensified tDCS had significant effects on momentary opioid craving reduction in all measured factors, e.g., desire and intention, negative reinforcement, and control (p ＜ 0.001). However, the results concerning treatment retention at the 3-month follow-up stage were insignificant for all factors (p ＜ 0.001). : Apparently, tDCS can be used as a tool to reduce craving. However, its application as an independent and sustainable treatment remains debatable.

Bioelectronic Direct Current Stimulation at the Transition Between Reversible and Irreversible Charge Transfer.

Many biological processes rely on endogenous electric fields (EFs), including tissue regeneration, cell development, wound healing, and cancer metastasis. Mimicking these biological EFs by applying external direct current stimulation (DCS) is therefore the key to many new therapeutic strategies. During DCS, the charge transfer from electrode to tissue relies on a combination of reversible and irreversible electrochemical processes, which may generate toxic or bio-altering substances, including metal ions and reactive oxygen species (ROS). Poly(3,4-ethylenedioxythiophene) (PEDOT) based electrodes are emerging as suitable candidates for DCS to improve biocompatibility compared to metals. This work addresses whether PEDOT electrodes can be tailored to favor reversible biocompatible charge transfer. To this end, different PEDOT formulations and their respective back electrodes are studied using cyclic voltammetry, chronopotentiometry, and direct measurements of H2O2 and O2. This combination of electrochemical methods sheds light on the time dynamics of reversible and irreversible charge transfer and the relationship between capacitance and ROS generation. The results presented here show that although all electrode materials investigated generate ROS, the onset of ROS can be delayed by increasing the electrode's capacitance via PEDOT coating, which has implications for future bioelectronic devices that allow longer reversibly driven pulse durations during DCS.

Cathodal bilateral transcranial direct-current stimulation regulates selenium to confer neuroprotection after rat cerebral ischaemia-reperfusion injury.

Non-invasive transcranial direct-current stimulation (tDCS) is a safe ischaemic stroke therapy. Cathodal bilateral tDCS (BtDCS) is a modified tDCS approach established by us recently. Because selenium (Se) plays a crucial role in cerebral ischaemic injury, we investigated whether cathodal BtDCS conferred neuroprotection via regulating Se-dependent signalling in rat cerebral ischaemia-reperfusion (I/R) injury. We first showed that the levels of Se and its transport protein selenoprotein P (SEPP1) were reduced in the rat cortical penumbra following I/R, whereas cathodal BtDCS prevented the reduction of Se and SEPP1. Interestingly, direct-current stimulation (DCS) increased SEPP1 level in cultured astrocytes subjected to oxygen-glucose deprivation reoxygenation (OGD/R) but had no effect on SEPP1 level in OGD/R-insulted neurons, indicating that DCS may increase Se in ischaemic neurons by enhancing the synthesis and secretion of SEPP1 in astrocytes. We then revealed that DCS reduced the number of injured mitochondria in OGD/R-insulted neurons cocultured with astrocytes. DCS and BtDCS prevented the reduction of the mitochondrial quality-control signalling, vesicle-associated membrane protein 2 (VAMP2) and syntaxin-4 (STX4), in OGD/R-insulted neurons cocultured with astrocytes and the ischaemic brain respectively. Under the same experimental conditions, downregulation of SEPP1 blocked DCS- and BtDCS-induced upregulation of VAMP2 and STX4. Finally, we demonstrated that cathodal BtDCS increased Se to reduce infract volume following I/R. Together, the present study uncovered a molecular mechanism by which cathodal BtDCS confers neuroprotection through increasing SEPP1 in astrocytes and subsequent upregulation of SEPP1/VAMP2/STX4 signalling in ischaemic neurons after rat cerebral I/R injury. KEY POINTS: Cathodal bilateral transcranial direct-current stimulation (BtDCS) prevents the reduction of selenium (Se) and selenoprotein P in the ischaemic penumbra. Se plays a crucial role in cerebral ischaemia injury. Direct-current stimulation reduces mitochondria injury and blocks the reduction of vesicle-associated membrane protein 2 (VAMP2) and syntaxin-4 (STX4) in oxygen-glucose deprivation reoxygenation-insulted neurons following coculturing with astrocytes. Cathodal BtDCS regulates Se/VAMP2/STX4 signalling to confer neuroprotection after ischaemia.

A translational roadmap for transcranial magnetic and direct current stimulation in stroke rehabilitation: Consensus-based core recommendations from the Third Stroke Recovery and Rehabilitation Roundtable

A translational roadmap for transcranial magnetic and direct current stimulation in stroke rehabilitation: Consensus-based core recommendations from the Third Stroke Recovery and Rehabilitation Roundtable