Cathodal Stimulation Research Articles

Mapping Spinal Cord Stimulation-Evoked Muscle Responses in Patients With Chronic Spinal Cord Injury

ObjectivesEpidural spinal cord stimulation (eSCS) has shown promise for restoring some volitional motor control after spinal cord injury (SCI). Maximizing therapeutic response requires effective spatial stimulation generated through careful configuration of anodes and cathodes on the eSCS lead. By exploring the way the spatial distribution of low frequency stimulation affects muscle activation patterns, we investigated the spatial specificity of stimulation-evoked responses for targeted muscle groups for restoration after chronic SCI (cSCI) in participants in the Epidural Stimulation After Neurologic Damage (E-STAND) trial. Materials and MethodsFifteen participants with Abbreviated Injury Scale A cSCI from the E-STAND study were evaluated with a wide range of bipolar spatial patterns. Surface electromyography captured stimulation-evoked responses from the rectus abdominis (RA), intercostal, paraspinal, iliopsoas, rectus femoris (RF), tibialis anterior (TA), extensor hallucis longus (EHL), and gastrocnemius muscle groups bilaterally. Peak-to-peak amplitudes were analyzed for each pulse across muscles. Stimulation patterns with dipoles parallel (vertical configurations), perpendicular (horizontal configurations), and oblique (diagonal configurations) relative to the rostral-caudal axis were evaluated. ResultsCathodic stimulation in the transverse plane indicated ipsilaterally biased activation in RA, intercostal, paraspinal, iliopsoas, RF, TA, EHL, and gastrocnemius muscles (p < 0.05). We found that caudal cathodic stimulation was significantly more activating only in the RF and EHL muscle groups than in the rostral (p < 0.037 and p < 0.006, respectively). Oblique stimulation was found to be more activating in the RA, intercostal, paraspinal, iliopsoas, and TA muscle groups than in the transverse (p < 0.05). ConclusionsCathodic stimulation provides uniform specificity for targeting laterality. Few muscle groups responded specifically to variation in rostral/caudal stimulation, and oblique stimulation improved stimulation responses when compared with horizontal configurations. These relations may enable tailored targeting of muscle groups, but the surprising amount of variation observed suggests that monitoring these evoked muscle responses will play a key role in this tailoring process. Clinical Trial RegistrationThe Clinicaltrials.gov registration number for the study is NCT03026816.

Anodal cerebellar stimulation increases cortical activation: Evidence for cerebellar scaffolding of cortical processing.

While the cerebellum contributes to nonmotor task performance, the specific contributions of the structure remain unknown. One possibility is that the cerebellum allows for the offloading of cortical processing, providing support during task performance, using internal models. Here we used transcranial direct current stimulation to modulate cerebellar function and investigate the impact on cortical activation patterns. Participants (n=74; 22.03 ± 3.44 years) received either cathodal, anodal, or sham stimulation over the right cerebellum before a functional magnetic resonance imaging scan during which they completed a sequence learning and a working memory task. We predicted that cathodal stimulation would improve, and anodal stimulation would hinder task performance and cortical activation. Behaviorally, anodal stimulation negatively impacted behavior during late-phase sequence learning. Functionally, we found that anodal cerebellar stimulation resulted in increased bilateral cortical activation, particularly in parietal and frontal regions known to be involved in cognitive processing. This suggests that if the cerebellum is not functioning optimally, there is a greater need for cortical resources.

Targeting Cerebellum with Non-Invasive Transcranial Magnetic or Current Stimulation after Cerebral Hemispheric Stroke-Insights for Corticocerebellar Network Reorganization: A Comprehensive Review.

Non-invasive brain stimulation (NIBS) has emerged as one of the methods implemented in stroke rehabilitation. Cerebellar stimulation has gained research interest as an alternative strategy to cortical stimulation, based on the role of the cerebellum and corticocerebellar tracts in different motor and cognitive functions. This review investigates the role of the cerebellum in motor and cognitive rehabilitation following cerebral stroke using NIBS techniques combined with other therapies (e.g., speech or physical therapy). Fifteen randomized clinical trials were included. The majority of the literature findings point towards the cerebellum as a promising neurostimulation target following stroke of the cerebral cortex. Findings concern mostly rehabilitation of gait and balance, where cathodal transcranial direct current stimulation (tDCS) and intermittent theta-burst stimulation (iTBS) of the contralesional cerebellar hemisphere produce, in the presented clinical sample, improved performance and plasticity changes in the corticocerebellar network, combined with other rehabilitation methods. Data regarding aphasia rehabilitation are scarce, with right cerebellar tDCS exercising some impact in individual linguistic functions combined with language therapy. Based on recent data concerning cerebellar functions and corticocerebellar networks, along with the development of clinical protocols regarding non-invasive cerebellar (NICS) application, the cerebellum can prove a crucial intervention target in rehabilitation following stroke.

Task-dependent plasticity in distributed neural circuits after transcranial direct current stimulation of the human motor cortex: A proof-of-concept study.

The ability of non-invasive brain stimulation to induce neuroplasticity and cause long-lasting functional changes is of considerable interest for the reversal of chronic pain and disability. Stimulation of the primary motor cortex (M1) has provided some of the most encouraging after-effects for therapeutic purposes, but little is known about its underlying mechanisms. In this study we combined transcranial Direct Current Stimulation (tDCS) and fMRI to measure changes in task-specific activity and interregional functional connectivity between M1 and the whole brain. Using a randomized counterbalanced sham-controlled design, we applied anodal and cathodal tDCS stimulation over the left M1. In agreement with previous studies, we demonstrate that tDCS applied to the target region induces task-specific facilitation of local brain activity after anodal tDCS, with the stimulation effects having a negative relationship to the resting motor threshold. Beyond the local effects, tDCS also induced changes in multiple downstream regions distinct from the motor system that may be important for therapeutic efficacy, including the operculo-insular and cingulate cortex. These results offer opportunities to improve outcomes of tDCS for the individual patient based on the degree of presumed neuroplasticity. Further research is still warranted to address the optimal stimulation targets and parameters for those with disease-specific symptoms of chronic pain.

Effects of transcranial direct current stimulation on neural activity and functional connectivity during fear extinction

Background/ObjectiveAnxiety disorders are highly prevalent and negatively impact daily functioning and quality of life. Transcranial direct current stimulation (tDCS) targeting the dorsolateral prefrontal cortex (dlPFC), especially in the right hemisphere impacts extinction learning; however, the underlying neural mechanisms are elusive. Therefore, we aimed to investigate the effects of cathodal tDCS stimulation to the right dlPFC on neural activity and connectivity patterns during delayed fear extinction in healthy participants. MethodsWe conducted a two-day fear conditioning and extinction procedure. On the first day, we collected fear-related self-reports, clinical questionnaires, and skin conductance responses during fear acquisition. On the second day, participants in the tDCS group (n = 16) received 20-min offline tDCS before fMRI and then completed the fear extinction session during fMRI. Participants in the control group (n = 18) skipped tDCS and directly underwent fMRI to complete the fear extinction procedure. Whole-brain searchlight classification and resting-state functional connectivity analyses were performed. ResultsWhole-brain searchlight classification during fear extinction showed higher classification accuracy of threat and safe cues in the left anterior dorsal and ventral insulae and hippocampus in the tDCS group than in the control group. Functional connectivity derived from the insula with the dlPFC, ventromedial prefrontal cortex, and inferior parietal lobule was increased after tDCS. ConclusiontDCS over the right dlPFC may function as a primer for information exchange among distally connected areas, thereby increasing stimulus discrimination. The current study did not include a sham group, and one participant of the control group was not randomized. Therefore, to address potential allocation bias, findings should be confirmed in the future with a fully randomized and sham controlled study.

Study protocol for evaluating the clinical efficacy and neurobiological correlates of sequential treatment with tDCS primed iTBS and ECT in treatment-resistant depression

Background: Treatment-resistant depression is a burdensome condition. Intermittent theta burst stimulation (iTBS) of the left dorsolateral prefrontal cortex is considered a treatment option in early course of resistance with a proportion of such patients responding to it. Preliminary evidence suggests a role of priming iTBS stimulation with preconditioning using cathodal transcranial direct current stimulation (tDCS). This protocol describes a double-blind randomized sham-controlled study to evaluate the clinical efficacy and tolerability of tDCS-primed iTBS in the treatment of resistant depression. Non-responders to this trial will be offered open-label electroconvulsive therapy. All participants will undergo neurobiological investigations that will enable the identification of potential response predictors and mechanisms. Methods: Three hundred and fifty consenting patients with treatment resistant depression will be randomly assigned to receive 20–30 daily sessions of true-tDCS or sham-tDCS primed iTBS over left dorsolateral prefrontal cortex at three study centers. After this blinded sham-controlled trial, non-responders to the intervention will be offered open-label true ECT. Clinical assessments, neurocognitive assessments and multimodal investigations (magnetic resonance imaging, electroencephalography, heart rate variability, investigative transcranial magnetic stimulation-transcranial direct current stimulation, gene polymorphisms) will be conducted at baseline and repeated after the end of the trial, as well as open-label ECT course. The trial will evaluate the improvement in depressive symptoms (Hamilton depression rating scale) between the two groups as the primary outcome measure.

Transcranial Direct-Current Stimulation Does Not Affect Implicit Sensorimotor Adaptation: A Randomized Sham-Controlled Trial.

Humans constantly calibrate their sensorimotor system to accommodate environmental changes, and this perception-action integration is extensively studied using sensorimotor adaptation paradigms. The cerebellum is one of the key brain regions for sensorimotor adaptation, but previous attempts to modulate sensorimotor adaptation with cerebellar transcranial direct current stimulation (ctDCS) produced inconsistent findings. Since both conscious/explicit learning and procedural/implicit learning are involved in adaptation, researchers have proposed that ctDCS only affects sensorimotor adaptation when implicit learning dominates the overall adaptation. However, previous research had both types of learning co-exist in their experiments without controlling their potential interaction under the influence of ctDCS. Here, we used error clamp perturbation and gradual perturbation, two effective techniques to elicit implicit learning only, to test the ctDCS effect on sensorimotor adaptation. We administrated ctDCS to independent groups of participants while they implicitly adapted to visual errors. In Experiment 1, we found that cerebellar anodal tDCS had no effect on implicit adaptation induced by error clamp. In Experiment 2, we applied both anodal and cathodal stimulation and used a smaller error clamp to prevent a potential ceiling effect, and replicated the null effect. In Experiment 3, we used gradually imposed visual errors to elicit implicit adaptation but still found no effect of anodal tDCS. With a total of 174 participants, we conclude that the previous inconsistent tDCS effect on sensorimotor adaptation cannot be explained by the relative contribution of implicit learning. Given that the cerebellum is simultaneously involved in explicit and implicit learning, our results suggest that the complex interplay between the two learning processes and large individual differences associated with this interplay might contribute to the inconsistent findings from previous studies on ctDCS and sensorimotor adaptation.

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

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

Unilateral cathodal transcranial direct current stimulation over the parietal area modulates postural control depending with eyes open and closed.

ObjectiveCathodal transcranial direct current stimulation (C-tDCS) is generally assumed to inhibit cortical excitability. The parietal cortex contributes to multisensory information processing in the postural control system, and this processing is proposed to be different between the right and left hemispheres and sensory modality. However, previous studies did not clarify whether the effects of unilateral C-tDCS of the parietal cortex on the postural control system differ depending on the hemisphere. We investigated the changes in static postural stability after unilateral C-tDCS of the parietal cortex.MethodsTen healthy right-handed participants were recruited for right- and left-hemisphere tDCS and sham stimulation, respectively. The cathodal electrode was placed on either the right or left parietal area, whereas the anodal electrode was placed over the contralateral orbit. tDCS was applied at 1.5 mA for 15 min. We evaluated static standing balance by measuring the sway path length (SPL), mediolateral sway path length (ML-SPL), anteroposterior sway path length (AP-SPL), sway area, and the SPL per unit area (L/A) after 15-minute C-tDCS under eyes open (EO) and closed (EC) conditions. To evaluate the effects of C-tDCS on pre- and post-offline trials, each parameter was compared using two-way repeated-measures analysis of variance (ANOVA) with factors of intervention and time. A post-hoc evaluation was performed using a paired t-test. The effect sizes were evaluated according to standardized size-effect indices of partial eta-squared (ηp2) and Cohen’s d. The power analysis was calculated (1-β).ResultsA significant interaction was observed between intervention and time for SPL (F (2, 27) = 4.740, p = 0.017, ηp2 = 0.260), ML-SPL (F (2, 27) = 4.926, p = 0.015, ηp2 = 0.267), and sway area (F (2, 27) = 9.624, p = 0.001, ηp2 = 0.416) in the EO condition. C-tDCS over the right hemisphere significantly increased the SPL (p < 0.01, d = 0.51), ML-SPL (p < 0.01, d = 0.52), and sway area (p < 0.05, d = 0.83) in the EO condition. In contrast, C-tDCS over the left hemisphere significantly increased the L/A in both the EC and EO condition (EO; p < 0.05, d = 0.67, EC; p < 0.05, d = 0.57).ConclusionThese results suggest that the right parietal region contributes to static standing balance through chiefly visual information processing during the EO condition. On the other hand, L/A increase during EC and EO by tDCS over the left parietal region depends more on somatosensory information to maintain static standing balance during the EC condition.

Transcranial direct current stimulation in stroke – Motor excitability and motor function

ObjectiveTo characterize motor excitability changes and changes of motor performance induced by a single anodal and cathodal transcranial direct current stimulation (tDCS) session in stroke patients. MethodsTwenty subacute stroke patients participated. Motor performance was tested with the Box and Block Test [BBT]. Motor cortex excitability (short interval intracortical inhibition [SICI], intracortical facilitation [ICF], long interval intracortical inhibition [LICI]) was examined by paired pulse transcranial magnetic stimulation before and after a single tDCS session (20 minutes, 1,0 mA). On two different occasions, patients received anodal and cathodal tDCS over the affected hemisphere. TMS recordings were taken from both hands consecutively. ResultsAnodal tDCS significantly reduced SICI without changing ICF or LICI. Cathodal tDCS did not change motor excitability. Both types of tDCS did not alter motor performance. Even prior to anodal tDCS, SICI in the affected hemisphere was lower than in the unaffected hemisphere and was correlated with BBT changes after anodal tDCS. ConclusionsAnodal, but not cathodal tDCS specifically modulated intracortical inhibitory circuits, leading to a disinhibition. SignificanceThe results amplify our knowledge on excitability modulations of tDCS in stroke patients.

Does high-definition transcranial direct current stimulation change brain electrical activity in professional female basketball players during free-throw shooting?

Differentiated brain activation in high-performance athletes supports neuronal mechanisms relevant to sports performance. Preparation for the motor action involves cortical and sub-cortical regions that can be non-invasively modulated by electrical current stimulation. This study aimed to investigate the effect of high-definition transcranial direct current stimulation (HD-tDCS) on electrical brain activity in professional female basketball players during free-throw shooting. Successful free-throw shooting (n = 2,361) from seven professional female basketball players was analyzed during two experimental conditions (HD-tDCS cathodic and sham) separated by 72 h. Three spectral bio-markers, Power Ratio Index (PRI), Delta Alpha Ratio (DAR), and Theta Beta Ratio (TBR) were measured (electroencephalography [EEG] Brain Products). Multi-channel HD-tDCS was applied for 20 min, considering current location and intensity for cathodic stimulation: FCC1h, AFF5h, AFF1h (-0.5 mA each), and FCC5h (ground). The within EEG analyses (pre and post HD-tDCS) of frontal channels (Fp1, Fp2, F3, F4, FC1, FC3) for 1 second epoch pre-shooting, showed increases in PRI (p < 0.001) and DAR (p < 0.001) for HD-tDCS cathodic condition, and in TBR for both conditions (cathodic, p = 0.01; sham, p = 0.002). Sub-group analysis divided the sample into less (n = 3; LSG) and more (n = 4; MSG) stable free-throw-shooting performers and revealed that increases in pre to post HD-tDCS in PRI only occurred for the LSG. These results suggest that the effect of HD-tDCS may induce changes in slow frontal frequency brain activities and that this alteration seems to be greater for players demonstrating a less stable free-throw shooting performance.

Repeated long sessions of transcranial direct current stimulation reduces seizure frequency in patients with refractory focal epilepsy: An open-label extension study

ObjectiveAlthough clinical trials have demonstrated that cathodal transcranial direct current stimulation (tDCS) is effective for seizure reduction, its long-term efficacy is unknown. This study aimed to determine the long-term effects of repeated cathodal long tDCS sessions on seizure suppression in patients with refractory epilepsy. MethodsPatients were recruited to participate in an extended phase of a previous randomized, double-blind, sham-controlled, three-arm, parallel, multicenter study on tDCS. The patients were divided into an active tDCS group (20 min of tDCS per day) and an intensified tDCS group (2 × 20 min of tDCS per day). Each tDCS session lasted 2 weeks and the patients underwent repeated sessions at intervals of 2 to 6 months. The cathode was placed over the epileptogenic focus with the current intensity set as 2 mA. Seizure frequency reduction from baseline was analyzed using the Wilcoxon signed-rank test for two related samples. A generalized estimating equation model was used to estimate group, time, and interaction effects. ResultsAmong the 19 patients who participated in the extended phase, 11 were in the active tDCS group and underwent 2–16 active tDCS sessions, and eight were in the intensified tDCS group and underwent 3–11 intensified tDCS sessions. Seizure reduction was significant from the first to the seventh follow-up, with a median seizure frequency reduction of 41.7%–83.3% (p < 0.05). Compared to the regular tDCS protocol, each intensified tDCS session substantially decreased seizure frequency by 0.3680 (p < 0.05). One patient experienced an increase of 8.5%–232.8% in the total number of seizures during three treatment sessions and follow-ups. ConclusionRepeated long cathodal tDCS sessions yielded significant and progressive long-term seizure reductions in patients with refractory focal epilepsy.

The impact of prefrontal transcranial direct current stimulation (tDCS) on theory of mind, emotion regulation and emotional-behavioral functions in children with autism disorder: A randomized, sham-controlled, and parallel-group study.

Advances in our knowledge about the neuropsychological mechanisms underlying core deficits in autism spectrum disorder (ASD) have produced several novel treatment modalities. One of these approaches is modulation of activity of the brain regions involved in ASD symptoms. This study examined the effects of transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) on autism symptom severity, theory of mind, emotion regulation strategies, and emotional-behavioral functions in children with ASD. Thirty-two children (Mage =10.16, SD=1.93, range 7-12 years) diagnosed with ASD were randomly assigned to active (N=17) or sham stimulation (N=15) groups in a randomized, sham-controlled, parallel-group design. Participants underwent 10 sessions of active (1.5mA, 15 min, bilateral left anodal/right cathodal DLPFC, 2 sessions per week) or sham tDCS. Autism symptom severity, theory of mind, emotion regulation strategies, and emotional-behavioral functioning of the patients were assessed at baseline, immediately after the intervention, and 1 month after the intervention. A significant improvement of autism symptom severity (i.e., communication), theory of mind (i.e., ToM 3), and emotion regulation strategies was observed for the active as compared to the sham stimulation group at the end of the intervention, and these effects were maintained at the one-month follow-up. The results suggest that repeated tDCS with anodal stimulation of left and cathodal stimulation of right DLPFC improves autism symptom severity as well as social cognition and emotion regulation in ASD. LAY SUMMARY: Previous research has suggested that targeting core mechanisms underlying cognitive-emotional and behavioral deficits of autistic children might improve symptoms of ASD. Deficient social and behavioral functioning, impaired theory of mind, and emotional regulation deficits have been identified as core treatment targets for this group. Specific subregions of the prefrontal cortex are involved in these deficits, including hypoactivity of the dorsolateral prefrontal cortex (DLPFC). Upregulation of this area with non-invasive brain stimulation, namely anodal transcranial direct current stimulation (tDCS), results in improved social and behavioral functioning in children with ASD. Very few studies have however examined the effects of this intervention on theory of mind, emotional regulation, and emotional-behavioral problems. We examined the effects of anodal tDCS over the left DLPFC (F3), combined with cathodal tDCS over the right DLPFC (F4) on autism symptom severity as well as theory of mind, emotional regulation, and emotional-behavioral problems of children with ASD. This intervention improved autism symptom severity, specific domains of theory of mind, and emotion regulation. These findings have clinical implications for the treatment of ASD and suggest that targeting core mechanisms underlying socio-cognitive-emotional deficits of autistic children using tDCS might improve symptoms of ASD.

Non-Invasive Transcutaneous Spinal DC Stimulation as a Neurorehabilitation ALS Therapy in Awake G93A Mice: The First Step to Clinical Translation.

Spinal direct current stimulation (sDCS) modulates motoneuron (MN) excitability beyond the stimulation period, making it a potential neurorehabilitation therapy for amyotrophic lateral sclerosis (ALS), a MN degenerative disease in which MN excitability dysfunction plays a critical and complex role. Recent evidence confirms induced changes in MN excitability via measured MN electrophysiological properties in the SOD1 ALS mouse during and following invasive subcutaneous sDCS (ssDCS). The first aim of our pilot study was to determine the clinical potential of these excitability changes at symptom onset (P90-P105) in ALS via a novel non-invasive transcutaneous sDCS (tsDCS) treatment paradigm on un-anesthetized SOD1-G93A mice. The primary outcomes were motor function and survival. Unfortunately, skin damage avoidance limited the strength of applied stimulation intensity, likewise limiting measurable primary effects. The second aim of this study was to determine which orientation of stimulation (anodal vs cathodal, which are expected to have opposing effects) is beneficial vs harmful in ALS. Despite the lack of measured primary effects, strong trends in survival of the anodal stimulation group, combined with an analysis of survival variance and correlations among symptoms, suggest anodal stimulation is harmful at symptom onset. Therefore, cathodal stimulation may be beneficial at symptom onset if a higher stimulation intensity can be safely achieved via subcutaneously implanted electrodes or alternative methods. Importantly, the many logistical, physical, and stimulation parameters explored in developing this novel non-invasive treatment paradigm on unanesthetized mice provide insight into an appropriate and feasible methodology for future tsDCS study designs and potential clinical translation.

Effects of cathodal transcranial direct current stimulation on hip range of motion of healthy sedentary women: A crossover study

The improvements in range of motion (ROM) by cathodal transcranial direct current stimulation (c-tDCS) were only found in sedentary men and not in females. Thus, the study investigated the effect of c-tDCS on hip flexion range of motion (HFROM) in sedentary women. Ten healthy (27.2 ± 6.4 years for age, 67.9 ± 17.8 kg for body mass, 159.1 ± 7.1 cm for height, and 87.1 ± 3.3° for HFROM) and right-leg-dominant women performed a counterbalanced crossover design in two experimental sessions, separated a week apart: c-tDCS and placebo stimulus (sham). Before and after experimental conditions (Pre-stimulation, Post-stimulation), participants had their HFROM measured. A significant interaction was demonstrated for conditions × time (F(1, 9) = 10.666; ƞ2 = 0.542; p = 0.01), indicating an increase in HFROM in the post-condition (89.0 ± 2.6°) compared to pre-condition (86.5° ± 2.9°) only in the c-tDCS. However, the HFROM improvements varied from 0.3 % to 6.5 % following c-tDCS. This study suggests that c-tDCS applied over the sensorimotor cortex of healthy sedentary women can acutely improve HFROM, but with a low percentage increase.

Transcranial direct current stimulation as a preventive treatment in multiple sclerosis? Preclinical evidence

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system, presenting with optic neuritis in about 20–30% of cases. Optic nerve demyelination, associated with delay of visual evoked potentials (VEPs), is also observed prior to motor signs in the preclinical MS model Experimental Autoimmune Encephalomyelitis (EAE). Transcranial direct current stimulation (tDCS), inducing polarity-dependent changes in neuronal excitability, is widely used to promote neuroplasticity in several neurological disorders. However, its potential effects on inflammation and demyelination are largely unknown. We tested the effectiveness of a preventive, 5-day tDCS treatment started 3 days post-immunization, in reducing the severity of VEP delays observed in early EAE. In mice undergoing cathodal tDCS (n = 6/26 eyes) VEPs were significantly less delayed compared with eyes from EAE-Sham (n = 24/32 eyes) and EAE-Anodal (n = 22/32 eyes). Optic nerve immunohistochemistry revealed a significantly lower cell density of microglia/macrophages, and less axonal loss in EAE-Cathodal vs EAE-Sham and EAE-Anodal, while the percent demyelination with Luxol-fast blue staining was comparable among EAE groups. Considering the latter result, immunofluorescence paranodal staining was performed, revealing a significantly higher number of complete paranode domains in EAE-Cathodal, closer to healthy mice, compared with EAE-Sham and EAE-Anodal groups. These results were reflected by the negative correlation between the number of complete paranode domains and VEP latency increase with respect to pre-immunization. Finally, cathodal tDCS was associated with a lower number, closer to healthy, of single paranodes in contrast to EAE-Sham. The effects of cathodal stimulation in preventing VEPs delays and optic nerve myelin damage were already observed in the pre-motor onset EAE stage, and were associated with a lower density of inflammatory cells. These findings suggest that tDCS may exert an anti-inflammatory effect with potential therapeutic application to be further explored in autoimmune demyelinating diseases.

The impact of cathodal tDCS on the GABAergic system in the epileptogenic zone: A multimodal imaging study.

ObjectivesWe aimed to investigate the antiepileptic effects of cathodal transcranial direct current stimulation (c-tDCS) and mechanisms of action based on its effects on the neurotransmitters responsible for the abnormal synchrony patterns seen in pharmacoresistant epilepsy. This is the first study to test the impact of neurostimulation on epileptiform interictal discharges (IEDs) and to measure brain metabolites in the epileptogenic zone (EZ) and control regions simultaneously in patients with pharmacoresistant epilepsy.MethodsThis is a hypothesis-driven pilot prospective single-blinded repeated measure design study in patients diagnosed with pharmacoresistant epilepsy of temporal lobe onset. We included seven patients who underwent two sessions of c-tDCS (sham followed by real). The real tDCS session was 20 min in duration and had a current intensity of 1.5 mA delivered via two surface electrodes that had dimensions of 3 × 4 cm. The cathode electrode was placed at FT7 in the center whereas the anode at Oz in the center. After each session, we performed electroencephalographic recording to count epileptiform IEDs over 30 min. We also performed magnetic resonance spectroscopy (MRS) to measure brain metabolite concentrations in the two areas of interest (EZ and occipital region), namely, gamma-aminobutyric acid (GABA), glutamate (Glx), and glutathione. We focused on a homogenous sample where the EZ and antiepileptic medications are shared among patients.ResultsReal tDCS decreased the number of epileptiform IEDs per min (from 9.46 ± 2.68 after sham tDCS to 5.37 ± 3.38 after real tDCS), p = 0.018, as compared to sham tDCS. GABA was decreased in the EZ after real c-tDCS stimulation as compared to sham tDCS (from 0.129 ± 0.019 to 0.096 ± 0.018, p = 0.02). The reduction in EZ GABA correlated with the reduction in the frequency of epileptiform IED per min (rho: 0.9, p = 0.003).ConclusionThese results provide a window into the antiepileptic mechanisms of action of tDCS, based on local and remote changes in GABA and neural oscillatory patterning responsible for the generation of interictal epileptiform discharges.

Neuromodulation of verb-transitivity judgments

This study aimed to further clarify the roles of the temporal and frontal lobes of the brain in the processing of verb argument structure. Left inferior frontal brain areas have long been considered important for sentence processing, but recent research links left posterior temporal cortex to knowledge of verb argument structure. We applied cathodal High-Definition transcranial Direct Current Stimulation to 45 participants in a between-subjects design, with 15 participants each for inferior-frontal-cortex stimulation, posterior-temporal-cortex stimulation, and sham stimulation. Set up as a training task during stimulation, participants made overt judgments on the number of participant roles associated with individual verbs. Stimulation of posterior temporal cortex did not yield results that were different from sham stimulation, speeding up task responses overall. By contrast, stimulation of inferior frontal cortex yielded differential results for intransitive versus transitive verbs, speeding up responses to intransitive verbs and increasing accuracy to transitive verbs, relative to other conditions. The transitivity effect, specific to inferior frontal stimulation, suggests a role for inferior frontal cortex in access to verb-argument-structure information, possibly specific to situations of high cognitive load and in which participant roles have to be established for production, as opposed to comprehension.

The effects of Single-Session Cathodal and Bihemispheric tDCS on Fluency in Stuttering

Developmental stuttering is a fluency disorder that adversely affect many aspects of a person's life. Recent transcranial direct current stimulation (tDCS) studies have shown promise to improve fluency in people who stutter. To date, bihemispheric tDCS has not been investigated in this population. In the present study, we aimed to investigate the effects of single-session bihemispheric and unihemispheric cathodal tDCS on fluency in adults who stutter. We predicted that bihemispheric tDCS with anodal stimulation to the left IFG and cathodal stimulation to the right IFG would improve fluency better than the sham and cathodal tDCS to the right IFG. Seventeen adults who stutter completed this single-blind, crossover, sham-controlled tDCS experiment. All participants received 20 min of tDCS alongside metronome-timed speech during intervention sessions. Three tDCS interventions were administered: bihemispheric tDCS with anodal stimulation to the left IFG and cathodal stimulation to the right IFG, unihemispheric tDCS with cathodal stimulation to the right IFG, and sham stimulation. Speech fluency during reading and conversation was assessed before, immediately after, and one week after each intervention session. There was no significant fluency improvement in conversation for any tDCS interventions. Reading fluency improved following both bihemispheric and cathodal tDCS interventions. tDCS montages were not significantly different in their effects on fluency.

High-Definition Transcranial Stimulation over the Dorsolateral Prefrontal Cortex Alters the Sunk Cost Effect: A Mental Accounting Framework.

The sunk cost effect refers to the fact that human decisions are consistently influenced by previous irrecoverable and irrelevant costs. Recent neuroimaging experiments suggest that the dorsolateral prefrontal cortex (dlPFC) plays a pivotal role in the sunk cost effect yet the causal and neurocomputational role of the dlPFC remains elusive. In this study, two cohorts of healthy human male and female adults were recruited to complete a novel two-step decision-making task during the anodal-sham or cathodal-sham high-definition transcranial direct current stimulation (HD-tDCS) over the dlPFC, respectively. Consistent with previous studies, we showed that the sunk cost deterred participants from making further investment and therefore engendered a de-escalation effect. Such behavior can be captured by a weighted mental accounting model with a recalibrated reference point in which the direction and magnitude of the sunk cost effects hinge on the decision weights apportioned to the option values. Interestingly, transcranial stimulation did not influence participants' initial willingness to incur sunk costs but only altered sunk costs' downstream effects. Specifically, anodal stimulation over the right dlPFC amplified the de-escalation effect of sunk costs whereas cathodal stimulation yielded the opposite result. HD-tDCS also changed the decision weights of the mental accounting model, providing a causal and computational link between PFC and sunk cost effects.SIGNIFICANCE STATEMENT Traditional economic theory assumes that decisions only concern the marginal costs and benefits yet human choices are notoriously susceptible to previously-incurred costs (termed the sunk cost effect). In the current study, we showed that direct current stimulation (DCS) of the right dorsolateral prefrontal cortex (dlPFC) altered sunk cost effects in participants' subsequent choices. Such effects can be captured by a mental accounting model where transcranial stimulation modulates the decision weights assigned to different options in the value integration process. These findings help elucidate the computational and causal role of the dlPFC in the context of sunk costs.