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Showing papers on "Transcranial direct-current stimulation published in 2020"


Journal ArticleDOI
TL;DR: This critical review identifies key priorities for future research into major depression and schizophrenia, including studies of the mechanism(s) of action of tDCS at the neuronal and systems levels, the establishment of the cognitive impact, as well as investigations of the potential clinical efficacy of tDCs.
Abstract: Transcranial direct current stimulation (tDCS) is a promising method for altering the function of neural systems, cognition, and behavior. Evidence is emerging that it can also influence psychiatric symptomatology, including major depression and schizophrenia. However, there are many open questions regarding how the method might have such an effect, and uncertainties surrounding its influence on neural activity, and human cognition and functioning. In the present critical review, we identify key priorities for future research into major depression and schizophrenia, including studies of the mechanism(s) of action of tDCS at the neuronal and systems levels, the establishment of the cognitive impact of tDCS, as well as investigations of the potential clinical efficacy of tDCS. We highlight areas of progress in each of these domains, including data that appear to favor an effect of tDCS on neural oscillations rather than spiking, and findings that tDCS administration to the prefrontal cortex during task training may be an effective way to enhance behavioral performance. Finally, we provide suggestions for further empirical study that will elucidate the impact of tDCS on brain and behavior, and may pave the way for efficacious clinical treatments for psychiatric disorders.

105 citations


Journal ArticleDOI
TL;DR: Both TMS and tDCS elicit a small trans-diagnostic effect on working memory, tDCS also improved attention/vigilance across diagnoses, and effects on the other domains were not significant.
Abstract: Background Cognition is commonly affected in brain disorders. Non-invasive brain stimulation (NIBS) may have procognitive effects, with high tolerability. This meta-analysis evaluates the efficacy of transcranial magnetic stimulation (TMS) and transcranial Direct Current Stimulation (tDCS) in improving cognition, in schizophrenia, depression, dementia, Parkinson's disease, stroke, traumatic brain injury, and multiple sclerosis. Methods A PRISMA systematic search was conducted for randomized controlled trials. Hedges' g was used to quantify effect sizes (ES) for changes in cognition after TMS/tDCS v. sham. As different cognitive functions may have unequal susceptibility to TMS/tDCS, we separately evaluated the effects on: attention/vigilance, working memory, executive functioning, processing speed, verbal fluency, verbal learning, and social cognition. Results We included 82 studies (n = 2784). For working memory, both TMS (ES = 0.17, p = 0.015) and tDCS (ES = 0.17, p = 0.021) showed small but significant effects. Age positively moderated the effect of TMS. TDCS was superior to sham for attention/vigilance (ES = 0.20, p = 0.020). These significant effects did not differ across the type of brain disorder. Results were not significant for the other five cognitive domains. Conclusions Our results revealed that both TMS and tDCS elicit a small trans-diagnostic effect on working memory, tDCS also improved attention/vigilance across diagnoses. Effects on the other domains were not significant. Observed ES were small, yet even slight cognitive improvements may facilitate daily functioning. While NIBS can be a well-tolerated treatment, its effects appear domain specific and should be applied only for realistic indications (i.e. to induce a small improvement in working memory or attention).

94 citations


Journal ArticleDOI
TL;DR: Individualised dose-control may reduce the variable effects of tDCS by reducing variability in electric field (E-field) intensities at a cortical target site with substantial variation observed throughout the brain.

93 citations


Journal ArticleDOI
TL;DR: Task-specific stimulation protocols can improve EFs in ADHD, with anodal left DLPFC tDCS most clearly affected executive control functions, while cathodalleft DLP FC tDCS improved inhibitory control.
Abstract: Objective: This study examined effects of transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC) on major executive functions ...

90 citations


Journal ArticleDOI
TL;DR: Transcranial direct current stimulation (tDCS) has shown mixed results for depression treatment and should be considered for further studies.
Abstract: Background Transcranial direct current stimulation (tDCS) has shown mixed results for depression treatment. Objective To perform a systematic review and meta-analysis of trials using tDCS to improve depressive symptoms. Methods A systematic review was performed from the first date available to January 06, 2020 in PubMed, EMBASE, Cochrane Library, and additional sources. We included randomized, sham-controlled clinical trials (RCTs) enrolling participants with an acute depressive episode and compared the efficacy of active versus sham tDCS, including association with other interventions. The primary outcome was the Hedges' g for continuous depression scores; secondary outcomes included odds ratios (ORs) and number needed to treat (NNT) for response, remission, and acceptability. Random effects models were employed. Sources of heterogeneity were explored via metaregression, sensitivity analyses, subgroup analyses, and bias assessment. Results We included 23 RCTs (25 datasets, 1,092 participants), most (57%) presenting a low risk of bias. Active tDCS was superior to sham regarding endpoint depression scores (k = 25, g = 0.46, 95% confidence interval [CI]: 0.22-0.70), and also achieved superior response (k = 18, 33.3% vs. 16.56%, OR = 2.28 [1.52-3.42], NNT = 6) and remission (k = 18, 19.12% vs. 9.78%, OR = 2.12 [1.42-3.16], NNT = 10.7) rates. Moreover, active tDCS was as acceptable as sham. No risk of publication bias was identified. Cumulative meta-analysis showed that effect sizes are basically unchanged since total sample reached 439 participants. Conclusions TDCS is modestly effective in treating depressive episodes. Further well-designed, large-scale RCTs are warranted.

85 citations


Journal ArticleDOI
TL;DR: TFUS can be used to modulate mood and emotional regulation networks in the prefrontal cortex by targeting the right inferior frontal gyrus, an area implicated in mood andotional regulation.
Abstract: Transcranial focused ultrasound (tFUS) is an emerging method for non-invasive neuromodulation akin to transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). tFUS offers several advantages over electromagnetic methods including high spatial resolution and the ability to reach deep brain targets. Here we describe two experiments assessing whether tFUS could modulate mood in healthy human volunteers by targeting the right inferior frontal gyrus (rIFG), an area implicated in mood and emotional regulation. In a randomized, placebo-controlled, double-blind study, participants received 30 s of 500 kHz tFUS or a placebo control. Visual Analog Mood Scales (VAMS) assessed mood four times within an hour (baseline and three times after tFUS). Participants who received tFUS reported an overall increase in Global Affect (GA), an aggregate score from the VAMS scale, indicating a positive shift in mood. Experiment 2 examined resting-state functional (FC) connectivity using functional magnetic resonance imaging (fMRI) following 2 min of 500 kHz tFUS at the rIFG. As in Experiment 1, tFUS enhanced self-reported mood states and also decreased FC in resting state networks related to emotion and mood regulation. These results suggest that tFUS can be used to modulate mood and emotional regulation networks in the prefrontal cortex.

83 citations


Journal ArticleDOI
TL;DR: To conclude, active tDCS was statistically superior to sham in all outcomes, although its clinical effects were moderate, and continuous clinical improvement was observed even after the end of acute tDCS treatment.
Abstract: We evaluated the efficacy and acceptability of transcranial direct current stimulation (tDCS) for treating acute depressive episodes using individual patient data that provide more precise estimates than aggregate data meta-analysis. A systematic review of placebo-controlled trials on tDCS as only intervention was conducted until December-2018. Data from each study was collated to estimate odds ratio (OR) and number needed to treat (NNT) of response and remission, and depression improvement. Endpoints were pre-determined. Nine eligible studies (572 participants), presenting moderate/high certainty of evidence, were included. Active tDCS was significantly superior to sham for response (30.9% vs. 18.9% respectively; OR = 1.96, 95%CI [1.30–2.95], NNT = 9), remission (19.9% vs. 11.7%, OR = 1.94 [1.19–3.16], NNT = 13) and depression improvement (effect size of β = 0.31, [0.15–0.47]). Moreover, continuous clinical improvement was observed even after the end of acute tDCS treatment. There were no differences in all-cause discontinuation rates and no predictors of response were identified. To conclude, active tDCS was statistically superior to sham in all outcomes, although its clinical effects were moderate.

80 citations


Journal ArticleDOI
TL;DR: Transcranial direct current stimulation was effective and safe in ameliorating negative symptoms in patients with schizophrenia and persistent negative symptoms persisted at follow-up.
Abstract: Importance Negative symptoms represent a substantial burden in schizophrenia. Although preliminary studies have suggested that transcranial direct current stimulation (tDCS) is effective for some clusters of symptoms, the clinical benefits for negative symptoms are unclear. Objective To determine the efficacy and safety of tDCS vs sham as an add-on treatment for patients with schizophrenia and predominant negative symptoms. Design, Setting, and Participants The double-blind Schizophrenia Treatment With Electric Transcranial Stimulation (STARTS) randomized clinical trial was conducted from September 2014 to March 2018 in 2 outpatient clinics in the state of Sao Paulo, Brazil. Patients with schizophrenia with stable negative and positive symptoms and a minimum score of 20 points in the negative symptoms subscale of the Positive and Negative Syndrome Scale (PANSS) were included. Interventions Ten sessions of tDCS performed twice a day for 5 days or a sham procedure. The anode and the cathode were positioned over the left prefrontal cortex and the left temporoparietal junction, respectively. Main Outcomes and Measures Change in the PANSS negative symptoms subscale score at week 6 was the primary outcome. Patients were followed-up for an additional 6 weeks. Results Of the 100 included patients, 20 (20.0%) were female, and the mean (SD) age was 35.3 (9.3) years. A total of 95 patients (95.0%) finished the trial. In the intention-to-treat analysis, patients receiving active tDCS showed a significantly greater improvement in PANSS score compared with those receiving the sham procedure (difference, 2.65; 95% CI, 1.51-3.79; number needed to treat, 3.18; 95% CI, 2.12-6.99;P Conclusions and Relevance Transcranial direct current stimulation was effective and safe in ameliorating negative symptoms in patients with schizophrenia. Trial Registration ClinicalTrials.gov identifier:NCT02535676

69 citations



Journal ArticleDOI
TL;DR: It is shown that properly parameterized computational models at multiple scales are needed to rationally optimize neuromodulation that target sets of cranial nerves, determining which and how specific brain circuitries are modulated, which can in turn influence cognition in a designed manner.

66 citations


Journal ArticleDOI
TL;DR: TDCS seems to be an effective adjuvant to conventional rehabilitation techniques if applied in the acute stages of stroke, functional recovery is not only accelerated, but improved, and results are maintained up to one year post stroke.

Journal ArticleDOI
TL;DR: Several risk factors of FOG have been identified, but need combinatorial optimization for predicting FOG more precisely and firm conclusions cannot be drawn on therapeutic efficacy, although the literature suggested that some therapeutic strategies showed promise.
Abstract: Freezing of gait (FOG) is a common, disabling symptom of Parkinson’s disease (PD), but the mechanisms and treatments of FOG remain great challenges for clinicians and researchers. The main focus of this review is to summarize the possible mechanisms underlying FOG, the risk factors for screening and predicting the onset of FOG, and the clinical trials involving various therapeutic strategies. In addition, the limitations and recommendations for future research design are also discussed. In the mechanism section, we briefly introduced the physiological process of gait control and hypotheses about the mechanism of FOG. In the risk factor section, gait disorders, PIGD phenotype, lower striatal DAT uptake were found to be independent risk factors of FOG with consistent evidence. In the treatment section, we summarized the clinical trials of pharmacological and non-pharmacological treatments. Despite the limited effectiveness of current medications for FOG, especially levodopa resistant FOG, there were some drugs that showed promise such as istradefylline and rasagiline. Non-pharmacological treatments encompass invasive brain and spinal cord stimulation, noninvasive repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) and vagus nerve stimulation (VNS), and physiotherapeutic approaches including cues and other training strategies. Several novel therapeutic strategies seem to be effective, such as rTMS over supplementary motor area (SMA), dual-site DBS, spinal cord stimulation (SCS) and VNS. Of physiotherapy, wearable cueing devices seem to be generally effective and promising. FOG model hypotheses are helpful for better understanding and characterizing FOG and they provide clues for further research exploration. Several risk factors of FOG have been identified, but need combinatorial optimization for predicting FOG more precisely. Although firm conclusions cannot be drawn on therapeutic efficacy, the literature suggested that some therapeutic strategies showed promise.

Journal ArticleDOI
TL;DR: TDCS‐fMRI can address important questions on the functional mechanisms of tDCS action and has the potential to support enhancement of behavioral interventions, provided studies are designed rationally.
Abstract: Understanding and reducing variability of response to transcranial direct current stimulation (tDCS) requires measuring what factors predetermine sensitivity to tDCS and tracking individual response to tDCS. Human trials, animal models, and computational models suggest structural traits and functional states of neural systems are the major sources of this variance. There are 118 published tDCS studies (up to October 1, 2018) that used fMRI as a proxy measure of neural activation to answer mechanistic, predictive, and localization questions about how brain activity is modulated by tDCS. FMRI can potentially contribute as: a measure of cognitive state-level variance in baseline brain activation before tDCS; inform the design of stimulation montages that aim to target functional networks during specific tasks; and act as an outcome measure of functional response to tDCS. In this systematic review, we explore methodological parameter space of tDCS integration with fMRI spanning: (a) fMRI timing relative to tDCS (pre, post, concurrent); (b) study design (parallel, crossover); (c) control condition (sham, active control); (d) number of tDCS sessions; (e) number of follow up scans; (f) stimulation dose and combination with task; (g) functional imaging sequence (BOLD, ASL, resting); and (h) additional behavioral (cognitive, clinical) or quantitative (neurophysiological, biomarker) measurements. Existing tDCS-fMRI literature shows little replication across these permutations; few studies used comparable study designs. Here, we use a representative sample study with both task and resting state fMRI before and after tDCS in a crossover design to discuss methodological confounds. We further outline how computational models of current flow should be combined with imaging data to understand sources of variability. Through the representative sample study, we demonstrate how modeling and imaging methodology can be integrated for individualized analysis. Finally, we discuss the importance of conducting tDCS-fMRI with stimulation equipment certified as safe to use inside the MR scanner, and of correcting for image artifacts caused by tDCS. tDCS-fMRI can address important questions on the functional mechanisms of tDCS action (e.g., target engagement) and has the potential to support enhancement of behavioral interventions, provided studies are designed rationally.

Journal ArticleDOI
TL;DR: Improvement of cognitive control functions is closely associated with reduced craving and Repeated DLPFC stimulation in order to improve executive control could be a promising approach for therapeutic interventions in drug addiction.

Journal ArticleDOI
TL;DR: These guidelines provide a reference and standard for practice when employing the use of tDCS outside of the clinic setting as well as to reach those in remote locations and/or living with more advanced disabilities.

Journal ArticleDOI
TL;DR: Several neuromodulation methods are of potential interest for migraine management, but the quality of the evidence is very poor.
Abstract: Several neuromodulation methods exists for migraine treatment. The aim of the present study was to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) focusing on migraine treatment using neurostimulation methods. We searched Medline and Embase up to July 1, 2020 for RCTs reporting acute or preventive treatment of migraine with either non-invasive or invasive neurostimulation methods. Two researchers independently assessed the eligibility of the retrieved studies and extracted data. Outcomes for the quantitative synthesis were 2 h pain free for acute treatment and headache days per month for preventive treatment. We performed subgroup analyses by treatment (stimulation method and site of application). Estimates were pooled using random-effects meta-analysis. Thirty-eight articles were included in the qualitative analysis (7 acute, 31 preventive) and 34 in the quantitative evaluation (6 acute, 28 preventive). Remote electrical neuromodulation (REN) was effective for acute treatment. Data were insufficient to draw conclusions for any other techniques (single studies). Invasive occipital nerve stimulation (ONS) was effective for migraine prevention, with a large effect size but considerable heterogeneity, whereas supra-orbital transcutaneous electrical nerve stimulation (TENS), percutaneous electrical nerve stimulation (PENS), and high-frequency repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (M1) were effective, with small to medium effect sizes. Vagus-nerve stimulation, left prefrontal cortex rTMS, and cathodal transcranial direct current stimulation (tDCS) over the M1 had no significant effect and heterogeneity was high. Several neuromodulation methods are of potential interest for migraine management, but the quality of the evidence is very poor. Future large and well-conducted studies are needed and could improve on the present results.

Journal ArticleDOI
TL;DR: TDCS‐induced excitability changes correlated more strongly with perfusion changes in the left sensorimotor region compared to the targeted hand‐knob region and with the predicted electric field, as simulated with finite element modeling.
Abstract: Transcranial direct current stimulation (tDCS) induces polarity- and dose-dependent neuroplastic aftereffects on cortical excitability and cortical activity, as demonstrated by transcranial magnetic stimulation (TMS) and functional imaging (fMRI) studies. However, lacking systematic comparative studies between stimulation-induced changes in cortical excitability obtained from TMS, and cortical neurovascular activity obtained from fMRI, prevent the extrapolation of respective physiological and mechanistic bases. We investigated polarity- and intensity-dependent effects of tDCS on cerebral blood flow (CBF) using resting-state arterial spin labeling (ASL-MRI), and compared the respective changes to TMS-induced cortical excitability (amplitudes of motor evoked potentials, MEP) in separate sessions within the same subjects (n = 29). Fifteen minutes of sham, 0.5, 1.0, 1.5, and 2.0-mA anodal or cathodal tDCS was applied over the left primary motor cortex (M1) in a randomized repeated-measure design. Time-course changes were measured before, during and intermittently up to 120-min after stimulation. ROI analyses indicated linear intensity- and polarity-dependent tDCS after-effects: all anodal-M1 intensities increased CBF under the M1 electrode, with 2.0-mA increasing CBF the greatest (15.3%) compared to sham, while all cathodal-M1 intensities decreased left M1 CBF from baseline, with 2.0-mA decreasing the greatest (-9.3%) from sham after 120-min. The spatial distribution of perfusion changes correlated with the predicted electric field, as simulated with finite element modeling. Moreover, tDCS-induced excitability changes correlated more strongly with perfusion changes in the left sensorimotor region compared to the targeted hand-knob region. Our findings reveal lasting tDCS-induced alterations in cerebral perfusion, which are dose-dependent with tDCS parameters, but only partially account for excitability changes.

Journal ArticleDOI
TL;DR: Recordings of single-unit activity in the hippocampus and visual cortex of alert monkeys receiving tACS are found to be consistent with the direct stimulation hypothesis and suggest that peripheral somatosensory stimulation is not required for tACs to entrain neurons.
Abstract: Transcranial alternating current stimulation (tACS) modulates brain activity by passing electrical current through electrodes that are attached to the scalp. Because it is safe and noninvasive, tACS holds great promise as a tool for basic research and clinical treatment. However, little is known about how tACS ultimately influences neural activity. One hypothesis is that tACS affects neural responses directly, by producing electrical fields that interact with the brain's endogenous electrical activity. By controlling the shape and location of these electric fields, one could target brain regions associated with particular behaviors or symptoms. However, an alternative hypothesis is that tACS affects neural activity indirectly, via peripheral sensory afferents. In particular, it has often been hypothesized that tACS acts on sensory fibers in the skin, which in turn provide rhythmic input to central neurons. In this case, there would be little possibility of targeted brain stimulation, as the regions modulated by tACS would depend entirely on the somatosensory pathways originating in the skin around the stimulating electrodes. Here, we directly test these competing hypotheses by recording single-unit activity in the hippocampus and visual cortex of alert monkeys receiving tACS. We find that tACS entrains neuronal activity in both regions, so that cells fire synchronously with the stimulation. Blocking somatosensory input with a topical anesthetic does not significantly alter these neural entrainment effects. These data are therefore consistent with the direct stimulation hypothesis and suggest that peripheral somatosensory stimulation is not required for tACS to entrain neurons.

Journal ArticleDOI
TL;DR: Overall, tDCS seems to be a promising method for improving ADHD deficits, however, the clinical utility of tDCS in ADHD cannot yet be concluded and requires further systematic investigation in larger sample sizes.
Abstract: Transcranial direct current stimulation (tDCS) is a promising method for altering cortical excitability with clinical implications. It has been increasingly used in neurodevelopmental disorders, especially attention-deficit hyperactivity disorder (ADHD), but its efficacy (based on effect size calculations), safety, and stimulation parameters have not been systematically examined. In this systematic review, we aimed to (1) explore the effectiveness of tDCS on the clinical symptoms and neuropsychological deficits of ADHD patients, (2) evaluate the safety of tDCS application, especially in children with ADHD, (3) model the electrical field intensity in the target regions based on the commonly-applied and effective versus less-effective protocols, and (4) discuss and propose advanced tDCS parameters. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses approach, a literature search identified 14 empirical experiments investigating tDCS effects in ADHD. Partial improving effects of tDCS on cognitive deficits (response inhibition, working memory, attention, and cognitive flexibility) or clinical symptoms (e.g., impulsivity and inattention) are reported in 10 studies. No serious adverse effects are reported in 747 sessions of tDCS. The left and right dorsolateral prefrontal cortex are the regions most often targeted, and anodal tDCS the protocol most often applied. An intensity of 2 mA induced stronger electrical fields than 1 mA in adults with ADHD and was associated with significant behavioral changes. In ADHD children, however, the electrical field induced by 1 mA, which is likely larger than the electrical field induced by 1 mA in adults due to the smaller head size of children, was sufficient to result in significant behavioral change. Overall, tDCS seems to be a promising method for improving ADHD deficits. However, the clinical utility of tDCS in ADHD cannot yet be concluded and requires further systematic investigation in larger sample sizes. Cortical regions involved in ADHD pathophysiology, stimulation parameters (e.g. intensity, duration, polarity, and electrode size), and types of symptom/deficit are potential determinants of tDCS efficacy in ADHD. Developmental aspects of tDCS in childhood ADHD should be considered as well.

Journal ArticleDOI
TL;DR: These results demonstrate for the first time that tDCS-linked WM training elicits lasting changes in behavior by optimizing the oscillatory substrates of prefrontal control.

Journal ArticleDOI
TL;DR: In this paper, home-based anodal (a)-transcranial direct current stimulation (tDCS) over dorsolateral prefrontal cortex (DLPFC) was used to improve the widespread pain and the disability related to pain.

Journal ArticleDOI
TL;DR: A duration threshold for reversal of the excitability-enhancing effect of a-tDCS with stimulation durations ≥ 26 min is confirmed, which might prevent excessive brain activation.

Journal ArticleDOI
01 Feb 2020-Cortex
TL;DR: The arguments against using electrical brain stimulation techniques in cognitive neuroscience are often overstated and elevate the risk of the field "throwing the baby out with the bath water", it is concluded.

Journal ArticleDOI
TL;DR: Reverse-calculation E-field modeling, alone or regressed against TES MT, shows promise as a method to individualize tDCS dose, and the large range of the reverse-calculated tDCS doses between subjects underscores the likely need to individualized tDCSdose.

Journal ArticleDOI
TL;DR: This prospective intervention in a large cohort of DoC patients strengthens the validity of the proposed EEG signatures of consciousness, and is suggestive of a direct causal effect of tDCS on consciousness.
Abstract: Severe brain injuries can lead to long-lasting disorders of consciousness (DoC) such as vegetative state/unresponsive wakefulness syndrome (VS/UWS) or minimally conscious state (MCS). While behavioral assessment remains the gold standard to determine conscious state, EEG has proven to be a promising complementary tool to monitor the effect of new therapeutics. Encouraging results have been obtained with invasive electrical stimulation of the brain, and recent studies identified transcranial direct current stimulation (tDCS) as an effective approach in randomized controlled trials. This non-invasive and inexpensive tool may turn out to be the preferred treatment option. However, its mechanisms of action and physiological effects on brain activity remain unclear and debated. Here, we stimulated 60 DoC patients with the anode placed over left-dorsolateral prefrontal cortex in a prospective open-label study. Clinical behavioral assessment improved in twelve patients (20%) and none deteriorated. This behavioral response after tDCS coincided with an enhancement of putative EEG markers of consciousness: in comparison with non-responders, responders showed increases of power and long-range cortico-cortical functional connectivity in the theta-alpha band, and a larger and more sustained P300 suggesting improved conscious access to auditory novelty. The EEG changes correlated with electric fields strengths in prefrontal cortices, and no correlation was found on the scalp. Taken together, this prospective intervention in a large cohort of DoC patients strengthens the validity of the proposed EEG signatures of consciousness, and is suggestive of a direct causal effect of tDCS on consciousness.

Journal ArticleDOI
TL;DR: Evidence is shown for two distinct cerebellar–cerebral interactions using Cerebellar stimulation in combination with directional transcranial magnetic stimulation (TMS) over M1, which suggests that there are two independent CB–M1 networks that contribute uniquely to different motor behaviors.
Abstract: Anterior-posterior (AP) and posterior-anterior (PA) pulses of transcranial magnetic stimulation (TMS) over the primary motor cortex (M1) appear to activate distinct interneuron networks that contribute differently to two varieties of physiological plasticity and motor behaviors (Hamada et al., 2014). The AP network is thought to be more sensitive to online manipulation of cerebellar (CB) activity using transcranial direct current stimulation. Here we probed CB-M1 interactions using cerebellar brain inhibition (CBI) in young healthy female and male individuals. TMS over the cerebellum produced maximal CBI of PA-evoked EMG responses at an interstimulus interval of 5 ms (PA-CBI), whereas the maximum effect on AP responses was at 7 ms (AP-CBI), suggesting that CB-M1 pathways with different conduction times interact with AP and PA networks. In addition, paired associative stimulation using ulnar nerve stimulation and PA TMS pulses over M1, a protocol used in human studies to induce cortical plasticity, reduced PA-CBI but not AP-CBI, indicating that cortical networks process cerebellar inputs in distinct ways. Finally, PA-CBI and AP-CBI were differentially modulated after performing two different types of motor learning tasks that are known to process cerebellar input in different ways. The data presented here are compatible with the idea that applying different TMS currents to the cerebral cortex may reveal cerebellar inputs to both the premotor cortex and M1. Overall, these results suggest that there are two independent CB-M1 networks that contribute uniquely to different motor behaviors.SIGNIFICANCE STATEMENT Connections between the cerebellum and primary motor cortex (M1) are essential for performing daily life activities, as damage to these pathways can result in faulty movements. Therefore, developing and understanding novel approaches to probe this pathway are critical to advancing our understanding of the pathophysiology of diseases involving the cerebellum. Here, we show evidence for two distinct cerebellar-cerebral interactions using cerebellar stimulation in combination with directional transcranial magnetic stimulation (TMS) over M1. These distinct cerebellar-cerebral interactions respond differently to physiological plasticity and to distinct motor learning tasks, which suggests they represent separate cerebellar inputs to the premotor cortex and M1. Overall, we show that directional TMS can probe two distinct cerebellar-cerebral pathways that likely contribute to independent processes of learning.

Journal ArticleDOI
TL;DR: Longitudinal brain age prediction is feasible and reliable in stroke patients and not significantly associated with response to cognitive training and minor brain lesions have minimal impact on brain age estimations.

Journal ArticleDOI
TL;DR: An up-to-date overview of the peripheral and central neurostimulation methods that can be used to treat chronic pain with special focus has been given to three pain conditions: neuropathic pain, nociplastic pain and primary headaches.
Abstract: The goal of this narrative review was to give an up-to-date overview of the peripheral and central neurostimulation methods that can be used to treat chronic pain. Special focus has been given to three pain conditions: neuropathic pain, nociplastic pain and primary headaches. Both non-invasive and invasive techniques are briefly presented together with their pain relief potentials. For non-invasive stimulation techniques, data concerning transcutaneous electrical nerve stimulation (TENS), transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), remote electrical neuromodulation (REN) and vagus nerve stimulation (VNS) are provided. Concerning invasive stimulation techniques, occipital nerve stimulation (ONS), vagus nerve stimulation (VNS), epidural motor cortex stimulation (EMCS), spinal cord stimulation (SCS) and deep brain stimulation (DBS) are presented. The action mode of all these techniques is only partly understood but can be very different from one technique to the other. Patients' selection is still a challenge. Recent consensus-based guidelines for clinical practice are presented when available. The development of closed-loop devices could be of interest in the future, although the clinical benefit over open loop is not proven yet.

Journal ArticleDOI
TL;DR: Evidence shows that tDCS may be more effective when used in combination with drugs and cognitive behavioral therapies; however future large-scale clinical trials are recommended to better clarify the real effects of this intervention alone, or in combinationWith others.
Abstract: Anxiety is one of the most prevalent and debilitating psychiatric conditions worldwide. Pharmaco- and psycho-therapies have been employed in the treatment of human anxiety to date. Yet, either alone or in combination, unsatisfactory patient outcomes are prevalent, resulting in a considerable number of people whose symptoms fail to respond to conventional therapies with symptoms remaining after intervention. The demand for new therapies has given birth to several noninvasive brain stimulation techniques. Transcranial direct current stimulation (tDCS) has arisen as a promising tool and has been proven to be safe and well tolerated for the treatment of many diseases, including chronic pain, depression, and anxiety. Here, reports of the use of tDCS in anxiety disorders in human patients were reviewed and summarized. A literature search was conducted in mid-2019, to identify clinical studies that evaluated the use of tDCS for the treatment of anxiety behavior. The PubMed, Web of Science, and Scielo and PsycInfo databases were explored using the following descriptors: "anxiety", "anxious behavior", "tDCS", and "transcranial direct current stimulation". Among the selected articles, considerable variability in the type of tDCS treatment applied in interventions was observed. Evidence shows that tDCS may be more effective when used in combination with drugs and cognitive behavioral therapies; however future large-scale clinical trials are recommended to better clarify the real effects of this intervention alone, or in combination with others.

Journal ArticleDOI
01 Jan 2020-Stress
TL;DR: Insight is provided into the efficacy of one single session of excitatory tDCS over the left DLPFC in attenuating autonomic and neuroendocrine effects of psychosocial stress exposure and this findings might be indicative of the important role of the left PFC, which is a cortical target for noninvasive brain stimulation treatment of depression, for successful coping with stressful stimuli.
Abstract: Prolonged or repeated activation of the stress response can have negative psychological and physical consequences. The prefrontal cortex (PFC) is thought to exert an inhibitory influence on...