Effects Of Direct Stimulation Research Articles

Acute effects of anodal transcranial direct current stimulation on endurance and maximal voluntary contraction in lower limbs: a systematic review and meta-analysis.

To examine the effects of single-dose anodal tDCS on isometric maximal voluntary contraction (MVC) and isometric endurance performance in lower limb exercises with healthy adults. For this systematic review and meta-analysis, we searched PubMed, ISI Web of Science, Scopus, and CINAHL for studies published between database inception and June 11, 2024. All randomized controlled trials on anodal tDCS interventions for MVC and isometric endurance in lower limb exercises were included, with no date restrictions. The quality of the evidence was assessed using the Jadad Scale, and the certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. The Open Science Framework registered the protocol in June 2024 (DOI https://doi.org/10.17605/OSF.IO/AG93M ). 20 interventions were included, comprising 15 for MVC and 5 for 'Time to Task Failure' (TTF), which refers to isometric endurance performance measured in seconds. The findings showed no difference in the MVC (SMD = 0.06; 95% CI = - 0.14, 0.25; P = 0.57) and TTF performance (WMD = 0.07; 95% CI = - 0.26, 0.40; P = 0.68). The current meta-analysis indicated that anodal tDCS did not increase isometric MVC and isometric endurance performance in lower limb exercises in healthy adults.

TDCS Cranial Nerve Co-Stimulation: Unveiling Brainstem Pathways Involved in Trigeminal Nerve Direct Current Stimulation in Rats.

The effects of transcranial direct current stimulation (tDCS) are generally thought to result from the polarization of cortical neurons by the weak electric fields it creates. However, recent evidence suggests that some tDCS effects may be mediated through co-stimulation of peripheral or cranial nerves, particularly the trigeminal nerve (TN). The TN projects to key brainstem nuclei that regulate neurotransmitter release throughout the central nervous system, but the specific pathways involved are not yet well understood. In this study, we examined the effects of acute transcutaneous TN direct current stimulation (TN-DCS) on tonic (i.e. mean spike rate) and phasic (number of bursts, spike rate per burst, burst duration, and inter-burst interval) activities while simultaneously recording single-neuron activity across three brainstem nuclei in rats: the locus coeruleus (LC; phasic and tonic activities), dorsal raphe nucleus (DRN; tonic activity), and median raphe nucleus (MnRN; tonic activity). TN-DCS significantly modulated tonic activity in the LC and DRN, with interactions between amplitude, polarity, and time affecting mean spike rates. It also influenced phasic activity in the LC, altering burst number, duration, and inter-burst intervals. In contrast, MnRN tonic activity was unchanged. Blocking TN with xylocaine eliminated the effects on tonic activity in both the LC and DRN. These results suggest that tDCS may modulate the TN, altering DRN and LC activity. Differential changes in tonic and phasic LC activity highlight their roles in TN-DCS effects on the cortex. This research offers insights to improve tDCS efficacy and understanding.

The polarity of high-definition transcranial direct current stimulation affects the planning and execution of movement sequences.

Noninvasive brain stimulation of the primary motor cortex has been shown to alter therapeutic outcomes in stroke and other neurological conditions, but the precise mechanisms remain poorly understood. Determining the impact of such neurostimulation on the neural processing supporting motor control is a critical step toward further harnessing its therapeutic potential in multiple neurological conditions affecting the motor system. Herein, we leverage the excellent spatio-temporal precision of magnetoencephalographic (MEG) imaging to identify the spectral, spatial, and temporal effects of high-definition transcranial direct current stimulation (HD-tDCS) on the neural responses supporting motor control. Participants (N = 67) completed three HD-tDCS visits (anode, cathode, sham), with each involving 20 minutes of left primary motor cortex stimulation and performance of a simple/complex motor sequencing task during MEG. Whole-brain statistical analyses of beta oscillatory responses revealed stimulation-by-task interaction effects in the left primary motor cortex, right occipitotemporal, and the right dorsolateral prefrontal cortices. Broadly, anodal stimulation induced significantly stronger beta oscillatory responses in these regions during simple movement sequences, while neural responses to complex sequences were not affected by stimulation. En masse, these data suggest that the beta oscillations serving motor planning (i.e., pre-movement) are particularly sensitive to the polarity of noninvasive stimulation and that the impact varies based on the difficulty of the movement sequence.

Comparing the Effects of CBT Plus tDCS or Pharmacotherapy on Depressive Symptoms, Inhibition, and Cognitive Flexibility in Stroke Patients: A Randomized Clinical Trial

Objectives The present study aims to compare the effects of cognitive-behavioral therapy (CBT) plus transcranial direct current stimulation (tDCS) or pharmacotherapy on depression symptoms, inhibition and cognitive flexibility of stroke patients Methods This is a randomized controlled clinical trial with a pre-test/post-test/follow-up design. The study population consists of all stroke sufferers referred to Dr. Hashemzehi's clinic in Zahedan, south of Iran, in 2022. The samples were 45 eligible patients who were selected by a convenience sampling method and randomly divided into three groups of 15 including CBT+tDCS, CBT+pharmacotherapy, and control. To measure depression, inhibition, and cognitive flexibility, we used Beck’s depression inventory, go/no go test, and Stroop test in the pre-test, post-test, and 2-month follow-up phases. The CBT was provided at 12 sessions according to Kootker et al.'s CBT protocol for stroke patients. The tDCS program was 20 sessions of anodal stimulation over the left dorsolateral prefrontal cortex. The pharmacotherapy was the administration of 10 mg citalopram daily for three weeks. Results The results indicated the short-term and long-term effectiveness of both CBT+tDCS and CBT + pharmacotherapy in reducing depression symptoms (P<0.05), and there was no significant difference between their effectiveness of . Only the CBT+tDCS had a short-term effect on improving inhibition and cognitive flexibility. Conclusion Both CBT+tDCS and CBT+pharmacotherapy (10 mg citalopram) can be useful for reducing depression symptoms in stroke sufferers.

The effect of transcranial direct current stimulation and inhibitory control training on depression and anxiety among post-stroke individuals

BackgroundRecent research has highlighted the role of fronto-parietal brain networks and cognitive control in mood disorders. Transcranial direct current stimulation (tDCS) and computer-based cognitive training are used in post-stroke rehabilitation. This study examined the combined effects ofof computer-based inhibitory control training (ICCT) and anodal tDCS on post-stroke depression and anxiety.MethodsThirty-five participants were randomly assigned to one of three groups: active tDCS treatment (A), sham tDCS treatment with ICCT (T), or active tDCS with ICCT (AT), for a duration of ten days. Primary outcome measures included the Beck Depression Inventory (BDI), Hamilton Depression Rating Scale (HAM-D), and Spielberger’s State-Trait Anxiety Inventory (STAI-S/T). Statistical analysis was performed using a Mixed-model Analysis of Variance, with supplementary Bayesian analysis.ResultsThe AT group showed a significant improvement in BDI scores (p < .001), whereas no significant effects were observed on the HAM-D, STAI-T, or STAI-S scales.ConclusionsThe combination of tDCS and ICCT reduced depressive symptoms as measured by the BDI; while no significant effects were found with either treatment alone. Further research is needed to explore the mechanisms behind the synergistic effects in the treatment of post-stroke mood disorders.

P0159 Effects of Transcranial Direct Current Stimulation (tDCS) on enteric nervous system (ENS) gene expression and intestinal barrier in chronic DSS colitis

Abstract Background Chronic visceral pain is a clinical challenge in &amp;gt;50% of Inflammatory Bowel Disease (IBD) cases. A randomized controlled trial (RCT) revealed that transcranial direct current stimulation (tDCS) can modulate brain activity and effectively alleviate chronic abdominal pain associated with IBD. To elucidate the underlying mechanism of tDCS, we implemented this technique in a mouse model of inflammatory, chronic DSS colitis. Methods The tDCS protocol (10 stimulations) was deduced from human tDCS studies. We administered an anodal direct current (0.5 mA, 20 min) to both primary motor cortices over two separate periods (5 consecutive days of stimulation per period separated by a two-day break). The study was controlled by a sham-tDCS group. For determining mucosal barrier integrity murine intestinal mucosa was mounted to Ussing chambers. Histology was done (H&amp;E staining of FFPE colon sections). Murine activity after tDCS was assessed by mouse tracking in home cages (RFID-chipped mice). Myenteric plexus (MP) cells from the murine terminal ileum, were isolated and cultivated for 10 days. Immunostaining and bulk-RNA sequencing (NovaSeq Xplus system, read length 150 bp, read depth 30 M copies/run) were performed. Results DSS caused an inflammation-driven thickening of the colon wall, resulting in an increased transmural resistance. This effect was ameliorated by tDCS (mean±SEM DSS+sham-tDCS: 72.2±8.2 Ω·cm²; DSS+tDCS: 48.1±2.1 Ω·cm²; MWU: p=0.007). Induction of a DSS colitis was associated with a reduced murine activity, which was partially recovered by tDCS (mean±SEM DSS+sham-tDCS: 70.7±15.2 rel.dist.U/day; DSS+tDCS: 205.9 ± 40.4 rel.dist.U/day; MWU: p=0.029). Neuronal cell identity was confirmed in isolated murine MP cells by immunostaining (b3-tubulin, S100B). Bulk-RNAseq significantly separated tDCS- from sham-tDCS treated DSS colitis mice as revealed by PCA. Consecutively, 739 differentially expressed genes were identified in tDCS-treated colitis mice compared to sham-tDCS-treated DSS colitic mice (622 upregulated, 117 downregulated genes; log2FC≥1.5, p-adj&amp;lt;0.05). KEGG and GO pathway analysis included neuroactive ligand-receptor interaction (p=7.94·10-3), gated channel activity (p=2.4·10-7), substrate-specific channel activity (p=1.99·10-7), leukocyte migration (p=3.99·10-7). Conclusion In colitis, tDCS has the capacity to modulate activity of DSS-treated mice and alters gene expression in MP cells. This reveals another layer of evidence for the impact of central pathways on the brain-gut-axis. References Neeb et al., Brain Stimulation, 2019

Effects of Dual-Site Anodal Transcranial Direct Current Stimulation on Attention, Decision-Making, and Working Memory during Sports Fatigue in Elite Soccer Athletes.

Sports fatigue in soccer athletes has been shown to decrease neural activity, impairing cognitive function and negatively affecting motor performance. Transcranial direct current stimulation (tDCS) can alter cortical excitability, augment synaptic plasticity, and enhance cognitive function. However, its potential to ameliorate cognitive impairment during sports fatigue remains largely unexplored. This study investigated the effect of dual-site tDCS targeting the dorsolateral prefrontal cortex (DLPFC) or primary motor cortex (M1) on attention, decision-making, and working memory in elite soccer athletes during sports fatigue. Sports fatigue was induced in 23 (non-goalkeeper) elite soccer athletes, who then participated in three counterbalanced intervention sessions: dual-site tDCS over the M1, dual-site tDCS over the DLPFC, and sham tDCS. Following tDCS, participants completed the Stroop, Iowa Gambling, and 2-back tasks. We found a significant improvement in Stroop task accuracy following dual-site anodal tDCS over the M1 compared with the sham intervention in the incongruent condition (p = 0.036). Net scores in the Iowa Gambling task during blocks 4 (p = 0.019) and 5 (p = 0.014) significantly decreased under dual-site tDCS targeting the DLPFC compared with the sham intervention. No differences in 2-back task performance were observed between sessions (all p > 0.05). We conclude that dual-site anodal tDCS applied to the M1 enhanced attention performance while tDCS targeting the DLPFC increased risk propensity in a decision-making task during sports fatigue in elite soccer athletes. However, dual-site anodal tDCS targeting either the M1 or DLPFC did not significantly influence working memory performance during sports fatigue in this population. These preliminary findings suggest that dual-site tDCS targeting the M1 has beneficial effects on attention performance, potentially informing future research on sports fatigue in athletes. No: NCT06594978. Registered 09 September, 2024; https://clinicaltrials.gov/search?cond=NCT06594978.

Neuromodulatory effect of transcranial direct current stimulation on cue reactivity and craving in young adults with internet gaming disorder: an event-related potential study.

This study assessed the effects of transcranial direct current stimulation (tDCS) on cue reactivity and craving for game-related cues using event-related potentials (ERPs) in internet gaming disorder (IGD) patients. At baseline, a series of game-related and neutral pictures were shown to both IGD and healthy controls (HCs) while ERPs were recorded. Late positive potentials (LPP) were used to investigate cue reactivity. During intervention, IGD patients received 10 sessions (two sessions/day for 5 consecutive days, 2 mA for 20 min/session) of tDCS to the left (anode stimulation) and right (cathode) dorsolateral prefrontal cortex. Subjectively assessed craving and LPP component was analyzed before stimulation and at the 1-month follow-up after tDCS in IGD. At baseline, patients with IGD showed higher LPP amplitudes for game-related cues in the centro-parietal and parietal regions than HCs. After 10 sessions of tDCS, increased LPP amplitudes decreased significantly at 1-month follow-up., as well as subjective craving for gaming. These findings suggest that neurophysiological arousal in response to game-related cues in the IGD group could be modulated by the effects of tDCS. LPP was a significant neurophysiological marker of the neuroplastic response of cue reactivity underlying the therapeutic effect of tDCS on IGD. Based on the present findings, tDCS could be expanded to the treatment of other addictive disorders, including substance use disorder and behavioral addictions.

The effects of transcranial direct current stimulation on global cognition in patients with Alzheimer's disease: An update meta-analysis.

Alzheimer's disease (AD) is a neurodegenerative disease. At present, there are currently no drugs that can cure AD. A number of empirical studies have shown that transcranial direct current stimulation (tDCS) may be used to treat cognitive abnormalities in patients with AD. We will through meta-analysis reviews tDCS overall research on the effects of cognitive function in patients with AD. Systematic searches were performed in the PubMed, Embase, and Cochrane Library databases from their creation until 8 March 2024. Using a fixed effect model and random effect model to evaluate the average difference between the treatment group and control group (MD) and its 95% confidence interval (CI). The study included 10 randomized controlled trials (Nactive = 165, Nsham = 167). The results of the overall analysis showed that tDCS did not significantly improve the overall cognitive function (SMD = 0.17; 95%CI = -0.05, 0.39; p = 0.14; I² = 51%). Quality of life of AD patients after treatment was also evaluated, but no improvement was seen. Subgroup analysis showed no significant improvement in global cognitive function after tDCS treatment. The sensitivity analysis to confirm the reliability of the data, risk assessment did not find any high-risk projects. The tDCS treatment did not improve cognitive function in patients with AD. Further empirical research in the future will help to explore new schemes for tDCS to improve cognitive function of patients.

Determining the safety, feasibility, and effects of anodal transcranial direct current stimulation on corticospinal excitability and quadriceps performance after anterior cruciate ligament reconstruction: a randomized crossover design

Determining the safety, feasibility, and effects of anodal transcranial direct current stimulation on corticospinal excitability and quadriceps performance after anterior cruciate ligament reconstruction: a randomized crossover design

The polarity effect of direct current stimulation on the vascular regulation of the inner retina

The polarity effect of direct current stimulation on the vascular regulation of the inner retina

Applications of transcranial direct current stimulation over vagus nerve on dysphagia after stroke.

Vagus nerve stimulation (VNS) has been commonly employed for the functional rehabilitation of stroke patients. This study aimed to investigate the therapeutic effects of transcranial direct current stimulation on the vagus nerve (TDCSVN) in improving dysphagia in stroke patients. Patients experiencing dysphagia following a stroke were diagnosed with dysphagia by a water swallow test. Swallowing function was evaluated with the standard swallowing scale score and the functional dysphagia scale. Serum levels of interleukin (IL)-1β and IL-8 were measured with enzyme-linked immunosorbent assays. TDCSVN treatment resulted in a significantly greater reduction in both the standard swallowing scale and functional dysphagia scale scores compared to conventional treatment. Furthermore, TDCSVN treatment led to a notable increase in hemoglobin and albumin levels, suggesting a more substantial improvement in dysphagia compared to conventional methods. Additionally, TDCSVN treatment was more effective in decreasing serum levels of IL-1β and IL-8 in dysphagic patients after a stroke. TDCSVN treatment demonstrated a significant inhibitory effect on inflammatory cytokines, resulting in a more pronounced improvement in dysphagia among stroke patients.NEW & NOTEWORTHY The present study demonstrates that transcranial direct current stimulation on the vagus nerve (TDCSVN) treatment shows a significant inhibitory effect on the production of inflammatory factors, resulting in a more pronounced improvement in dysphagia among stroke patients.

The Effect of Transcranial Direct Current Stimulation (tDCS) on Depression Symptoms in Patients with Chronic Low Back Pain: A Systematic Review and Meta-Analysis

The Effect of Transcranial Direct Current Stimulation (tDCS) on Depression Symptoms in Patients with Chronic Low Back Pain: A Systematic Review and Meta-Analysis

INFOGRAPHIC: Effects of transcranial direct current stimulation on enhancing motor training gains in people with Parkinson's Disease

In people with Parkinson's disease (PwPD) occurs the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta, which are responsible for producing dopamine—a neurotransmitter that, among other roles, regulates cortical activation. That degeneration leads to reduced excitatory activation of the thalamus over the primary motor cortex and increased inhibitory activation of the basal ganglia on the pedunculopontine nucleus and the reticular formation. The result is hypoactivation of regions involved in motor responses, particularly those responsible for balance and locomotion control in PwPD 1. Research has shown that physical interventions can positively affect the symptoms of PD 2. In recent years, evidence has accumulated that transcranial direct current stimulation (tDCS) can be used as a non-invasive procedure for treating PwPD, showing promising results in enhancing the effects of motor training3. The manuscript presents the theoretical background on the potential of anodal tDCS to increase motor training gains in PwPD. Transcranial direct current stimulation involves the application of a low-intensity electrical current (typically 2–4 mA) to the scalp, aiming to modulate the activity of cortical and subcortical neurons. The mechanism of tDCS operates through a subthreshold shift in neuronal resting potential, achieved via anodic or cathodic stimulation. In PwPD, anodal stimulation is more commonly employed, as it induces depolarization of neuronal membranes. Additionally, studies have observed increased dopamine release in the caudate nucleus and striatum 4. Further supporting its therapeutic potential in making the neural environment more conducive to activation when recruited. Previous studies conducted by our group demonstrated that combining tDCS with aerobic exercise amplifies the benefits in acute (single session) 5. Additionally, preliminary unpublished data indicate positive effects of chronic (multi-session) tDCS when combined with body balance training protocols. These studies highlighted the potential of tDCS to enhance outcomes in gait impairments when paired with aerobic exercise, as well as in postural instability when combined with balance training (see Beretta et al. 3, for a review). As tDCS is a technique still under development, the literature lacks a standardized protocol for stimulation parameters that optimize its effectiveness in treating PwPD. Consequently, it is usual to find studies with similar objectives employing varying stimulation intensities and target regions. Despite these differences, studies investigating the application of anodal tDCS during motor training in PwPD—regardless of intensity or location—suggest that electrical stimulation acts antagonistically to hypoactivation by facilitating the use of neural resources during the intervention. Thus, it seems to enhance the training outcome, leading to more effective results 5.

Effect of transcranial direct current stimulation on handgrip strength training in amateur badminton players

Objective. The objective of this study was to explore the effect of transcranial direct current stimulation (tDCS) combined with hand grip strengthening exercises in amateur badminton players. Materials and methods. This study was a participant-blinded, randomized controlled trial. Thirty amateur badminton players, aged 8–20 years with a minimum playing experience of 6 months, were included. Hand grip strength (HGS) was measured at baseline, Day 1, Day 4, Day 8, and Day 12. Results. The results of the present study showed no significant difference in hand grip strength between the groups. The overall interaction effect between the groups was found to be insignificant (p = 0.722). However, the overall interaction effect within the group was significant (p = 0.011*). Multiple comparisons revealed the greatest improvement in HGS at Day 12 compared to the baseline value. Conclusion. The application of anodal tDCS combined with HGS training was ineffective in improving hand grip strength in amateur badminton players.

Effects of Transcranial and Trans-Spinal Direct Current Stimulation Combined with Robot-Assisted Gait Training on Gait and Fatigue in Patients with Multiple Sclerosis: A Double-Blind, Randomized, Sham-Controlled Study.

Background/Objectives: Multiple Sclerosis (MS) is a chronic neurological condition that impairs motor and sensory functions, particularly gait. Non-invasive neuromodulation techniques aim to enhance functional recovery and motor-cognitive outcomes, though their effectiveness remains debated. This study compared the effects of transcranial direct current stimulation (tDCS) and trans-spinal direct current stimulation (tsDCS), combined with robotic-assisted gait training (RAGT), on motor function and fatigue in people with MS (pwMS). Methods: This double-blind, randomized, sham-controlled clinical trial included 35 pwMS, who participated in 12 sessions of 20 min anodal tDCS (n = 11), cathodal tsDCS (n = 12), or sham treatment (n = 12), in addition to RAGT. Primary outcomes were assessed using the Timed 25-foot Walk (T25-FW), Timed Up and Go (TUG), walking speed, and Multiple Sclerosis Walking Scale-12 (MSWS-12). Fatigue was assessed with the Fatigue Severity Scale (FSS) and the Fatigue Impact Scale (FIS). ClinicalTrials number: NCT06121635. Results: Significant improvements in gait speed, T25-FW, MSWS-12, TUG scores, and fatigue (FSS) favored tDCS and tsDCS over sham stimulation. While no differences were found between tDCS and tsDCS, the tsDCS group showed a significant improvement in the FIS physical subscale compared to sham, unlike the tDCS group. Conclusions: tDCS and tsDCS, combined with RAGT, improve walking and reduce fatigue in pwMS, highlighting their potential in motor rehabilitation.

Effects of Different Transcranial Direct Current Stimulation Intensities over Dorsolateral Prefrontal Cortex on Brain Electrical Activity and Heart Rate Variability in Healthy and Fibromyalgia Women: A Randomized Crossover Trial

People with fibromyalgia (FM) exhibit alterations in brain electrical activity and autonomic modulation compared to healthy individuals. Objectives: This study aimed to investigate transcranial direct current stimulation (tDCS) effects on brain electrocortical activity and heart rate variability (HRV), specifically targeting the dorsolateral prefrontal cortex in both healthy controls (HC) and FM groups, to identify potential differences in the responses between these groups, and to compare the effectiveness of two distinct tDCS intensities (1 mA and 2 mA) against a sham condition. Methods: Electroencephalography and electrocardiogram signals were recorded pre- and post-tDCS intervention. All participants underwent the three conditions (sham, 1 mA, and 2 mA) over three separate weeks, randomized in order. Results: No statistically significant baseline differences were found in the investigated HRV variables. In the FM group, 1 mA tDCS induced significant increases in LF, LF/HF, mean HR, SDNN, RMSSD, total power, SD1, SD2, and SampEn, and a decrease in HF, suggesting a shift toward sympathetic dominance. Additionally, 2 mA significantly increased SampEn compared to sham and 1 mA. In the HC group, sham increased DFA1 compared to 1 mA, and 2 mA induced smaller changes in SampEn relative to sham and 1 mA. No significant differences were found between FM and HC groups for any tDCS intensity. Conclusions: The effects of dlPFC-tDCS on HRV are intensity- and group-dependent, with the FM group exhibiting more pronounced changes at 1 mA and 2 mA. These findings emphasize the need for individualized stimulation protocols, given the variability in responses across groups and intensities.

Effect of home-based transcranial direct current stimulation (tDCS) on cognitive functioning in bipolar depression.

Bipolar depression is commonly accompanied by cognitive impairments. Transcranial direct current stimulation (tDCS) is emerging as a novel non-invasive treatment for bipolar depression. Given the portability and safety of tDCS, we developed a home-based protocol with real-time supervision. Our aim was to assess the cognitive effects of tDCS in bipolar disorder. 44 participants (31 women, mean age 47.27 ± 12.89 years) experiencing a moderate to severe depressive episode received 21 sessions of home-based tDCS over 6 weeks. The stimulation protocol involved 2 mA in a bilateral frontal montage (F3 anode, F4 cathode) for 30 minutes per session. The cognitive assessments were conducted at baseline and after the course of treatment. Rey Auditory Verbal Learning Test (RAVLT) was used to assess verbal learning and memory and the Symbol Digit Modalities Test (SDMT) to assess psychomotor processing speed and visuospatial attention. 93.18% (n=41) completed RAVLT and 59.09% of participants (n=26) completed SDMT. A significant improvement was observed in the RAVLT short-term verbal memory score post-treatment (p = 0.002). Improvements were observed in RAVLT verbal learning, RAVLT post-interference recall, and SDMT, which were not statistically significant. In summary, cognitive performance showed an improvement in bipolar depression following treatment with home-based tDCS, suggesting it can be an effective intervention for cognitive deficits in bipolar depression and positively impact cognitive function.

Calcium-sensor proteins but not bicarbonate ion activate retinal photoreceptor membrane guanylyl cyclase in photoreceptors

Retinal membrane guanylyl cyclase (RetGC), regulated by guanylyl cyclase activating proteins (GCAPs) via negative calcium-feedback, is one of the most critically important enzymes in vertebrate rod and cone physiology, enabling their sensitivity to light. It was also reported that, similarly to olfactory receptor guanylyl cyclase, bicarbonate anion directly stimulates RetGC activity in photoreceptors as a novel phototransduction-linked regulating factor. We directly tested whether or not RetGC is a bicarbonate-activated enzyme using recombinant human RetGC expressed in HEK293 cells and the native RetGC in mouse retinas. Whereas RetGC in all cases was activated by GCAPs, we found no evidence indicating that bicarbonate can produce direct stimulating effect on RetGC catalytic activity, either basal or GCAP-activated, even at concentrations as high as 100 mM. Instead, near-physiological concentrations of bicarbonate only slightly reduced RetGC activity, whereas concentrations substantially exceeding physiological levels caused a more pronounced reduction of RetGC activity measured in mouse retinas. Our results argue that photoreceptor guanylyl cyclase is not a bicarbonate-stimulated enzyme and rule out the possibility that effects of bicarbonate on photoreceptor physiology are mediated by a direct stimulation of retinal guanylyl cyclase by HCO3−.

Immediate Effects of Distinct Intensities of Transcutaneous Spinal Direct Current Stimulation on Chronic Pain: A Randomized Controlled Trial.

This study aimed to assess the immediate effects of transcutaneous spinal direct current stimulation (tsDCS) on pain outcomes, measured using the visual analog scale (VAS) and pressure pain thresholds in a cohort of 55 participants experiencing chronic pain using a controlled, randomized trial with 55 participants allocated into 2 groups: 2 mA and 0.5 mA of tsDCS for 20 min. Anodal stimulation was applied on the 12th thoracic vertebra, with the cathode positioned on the 7th cervical vertebra. Pain outcomes were assessed before and post intervention using the VAS and pressure algometry. Between- and within-group differences, along with chi-square tests, were used to determine the differences and responsiveness. Significance was established at p < 0.05. Findings showed significant temporal effects for both VAS (p < 0.001) and pressure algometry (p = 0.04). However, no between-group differences were noted for the time × group factor for VAS (p = 0.46) and pressure algometry (p = 0.78). No significant between-group differences were observed for the responsiveness analysis. The results indicate that a single 20-min session of 2 and 0.5 mA tsDCS improves pain scores for both intensities equally. However, there were no statistically significant between-group differences in pain perception or pressure pain threshold.