Combined therapy of bilateral transcranial direct current stimulation and ocular occlusion improves visual function in adults with amblyopia, a randomized pilot study.

Background: Amblyopia is the interocular visual acuity difference of two lines or more with the best correction in both eyes. It is treated with ocular occlusion therapy, but its success depends on neuroplasticity, and thus is effective in children but not adults. Transcranial Direct Current Stimulation (tDCS) is suggested to increase neuroplasticity. Objective: To determine if combined intervention of bilateral tDCS and ocular occlusion improves visual function in adults with amblyopia. Methods: A double-blind randomized, controlled pilot trial was conducted in 10 volunteers with amblyopia. While applying ocular occlusion and performing a reading task, participants received bilateral tDCS (n = 5) or sham stimulation (n = 5), with the anodal tDCS electrode in the contralateral visual cortex and the cathodal in the ipsilateral visual cortex in relation to the amblyopic eye. Visual function (through visual acuity, stereopsis, and contrast sensitivity tests) and visual evoked potential (with checkerboard pattern stimuli presentation) were evaluated immediately after. Results: A total of 30 min after treatment with bilateral tDCS, visual acuity improved by 0.16 (± 0.025) LogMAR in the treatment group compared with no improvement (-0.02 ± 0.02) in five controls (p = 0.0079), along with a significant increase in the amplitude of visual evoked potentials of the amblyopic eye response (p = 0.0286). No significant changes were observed in stereopsis and contrast sensitivity. No volunteer reported any harm derived from the intervention. Conclusion: Our study is the first to combine anodal and cathodal tDCS for the treatment of amblyopia, showing transient improved visual acuity in amblyopic adults.

Effects of Hypnotic Analgesia and Transcranial Direct Current Stimulation on Pain Tolerance and Corticospinal Excitability in Individuals with Fibromyalgia: A Cross-Over Randomized Clinical Trial.

Objective: We compare the effect of HAS, a-tDCS on the left dorsolateral prefrontal cortex (l-DLPFC), and rest-testing on pain measures [(cold pressor test (CPT) (primary outcome) and heat pain threshold]. We also compare their effects on the motor evoked potential (MEP) (primary outcome), short intracortical inhibition (SICI), intracortical facilitation (ICF), and cortical silent period (CSP). Methods: This randomized, blind, crossover trial included 18 women with fibromyalgia, aged from 18 to 65 years old. They received at random and in a crossover order a-tDCS over the l-DLPFC (2mA), HAS, or a rest-testing. Results: HAS compared to a-tDCS increased the pain tolerance with a moderate effect size (ES) [Cohen's f=-0.78; (CI 95%; -1.48 to -0.12)]. While compared to rest-testing, HAS increased the CPT with a large ES [Cohen's f=-0.87; (CI 95%; -1.84 to -0.09)]. The a-tDCS compared to HAS increased the MEP amplitude with large ES [Cohen's f=-1.73 (CI 95%; -2.17 to -0.17)]. Likewise, its ES compared to rest-testing in the MEP size was large [Cohen's f=-1.03; (CI 95%; -2.06 to -0.08)]. Conclusion: These findings revealed that HAS affects contra-regulating mechanisms involved in perception and pain tolerance, while the a-tDCS increased the excitability of the corticospinal pathways. They give a subsidy to investigate their effect as approaches to counter regulate the maladaptive neuroplasticity involved in fibromyalgia. Clinical Trial Registration: www.ClinicalTrials.gov, identifier - NCT05066568.

Feasibility, acceptability and practicality of transcranial stimulation in obsessive compulsive symptoms (FEATSOCS): A randomised controlled crossover trial.

BACKGROUND: Transcranial direct current stimulation (tDCS) is a non-invasive form of neurostimulation with potential for development as a self-administered intervention. It has shown promise as a safe and effective treatment for obsessive compulsive disorder (OCD) in a small number of studies. The two most favourable stimulation targets appear to be the left orbitofrontal cortex (L-OFC) and the supplementary motor area (SMA). We report the first study to test these targets head-to-head within a randomised sham-controlled trial. Our aim was to inform the design of future clinical research studies, by focussing on the acceptability and safety of the intervention, feasibility of recruitment, adherence to and tolerability of tDCS, and the size of any treatment-effect. METHODS: FEATSOCS was a randomised, double-blind, sham-controlled, cross-over, multicentre study. Twenty adults with DSM-5-defined OCD were randomised to treatment, comprising three courses of clinic-based tDCS (SMA, L-OFC, Sham), randomly allocated and delivered in counterbalanced order. Each course comprised four 20-min 2 mA stimulations, delivered over two consecutive days, separated by a 'washout' period of at least four weeks. Assessments were carried out by raters who were blind to stimulation-type. Clinical outcomes were assessed before, during, and up to four weeks after stimulation. Patient representatives with lived experience of OCD were actively involved at all stages. RESULTS: Clinicians showed willingness to recruit participants and recruitment to target was achieved. Adherence to treatment and study interventions was generally good, with only two dropouts. There were no serious adverse events, and adverse effects which did occur were transient and mostly mild in intensity. Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores were numerically improved from baseline to 24 h after the final stimulation across all intervention groups but tended to worsen thereafter. The greatest effect size was seen in the L-OFC arm, (Cohen's d = -0.5 [95% CI -1.2 to 0.2] versus Sham), suggesting this stimulation site should be pursued in further studies. Additional significant sham referenced improvements in secondary outcomes occurred in the L-OFC arm, and to a lesser extent with SMA stimulation. CONCLUSIONS: tDCS was acceptable, practicable to apply, well-tolerated and appears a promising potential treatment for OCD. The L-OFC represents the most promising target based on clinical changes, though the effects on OCD symptoms were not statistically significant compared to sham. SMA stimulation showed lesser signs of promise. Further investigation of tDCS in OCD is warranted, to determine the optimal stimulation protocol (current, frequency, duration), longer-term effectiveness and brain-based mechanisms of effect. If efficacy is substantiated, consideration of home-based approaches represents a rational next step. TRIAL REGISTRATION: ISRCTN17937049. https://doi.org/10.1186/ISRCTN17937049.

The therapeutic potential of non-invasive brain stimulation for the treatment of Long-COVID-related cognitive fatigue.

Following an acute COVID-19 infection, a large number of patients experience persisting symptoms for more than four weeks, a condition now classified as Long-COVID syndrome. Interestingly, the likelihood and severity of Long-COVID symptoms do not appear to be related to the severity of the acute COVID-19 infection. Fatigue is amongst the most common and debilitating symptoms of Long-COVID. Other symptomes include dyspnoea, chest pain, olfactory disturbances, and brain fog. Fatigue is also frequently reported in many other neurological diseases, affecting a broad range of everyday activities. However, despite its clinical significance, limited progress has been made in understanding its causes and developing effective treatment options. Non-invasive brain stimulation (NIBS) methods offer the unique opportunity to modulate fatigue-related maladaptive neuronal activity. Recent data show promising results of NIBS applications over frontoparietal regions to reduce fatigue symptoms. In this current paper, we review recent data on Long-COVID and Long-COVID-related fatigue (LCOF), with a special focus on cognitive fatigue. We further present widely used NIBS methods, such as transcranial direct current stimulation, transcranial alternating current stimulation, and transcutaneous vagus nerve stimulation and propose their use as possible therapeutic strategies to alleviate individual pathomechanisms of LCOF. Since NIBS methods are safe and well-tolerated, they have the potential to enhance the quality of life in a broad group of patients.

The influence of a single transcranial direct current stimulation session on physical fitness in healthy subjects: a systematic review.

Physical fitness is of indisputable importance for both health, and sports. Currently, the brain is being increasingly recognized as a contributor to physical fitness. Hereby, transcranial direct current stimulation (tDCS), as an ergogenic aid, has gained scientific interest. The current PRISMA-adherent review aimed to examine the effect of tDCS on the three core components of physical fitness: muscle strength, -endurance and cardiopulmonary endurance. Randomized controlled- or cross-over trials evaluating the effect of a single tDCS session (vs. sham) in healthy individuals were included. Hereby, a wide array of tDCS-related factors (e.g., tDCS montage and dose) was taken into account. Thirty-five studies (540 participants) were included. Between-study heterogeneity in factors such as age, activity level, tDCS protocol, and outcome measures was large. The capacity of tDCS to improve physical fitness varied substantially across studies. Nevertheless, muscle endurance was most susceptible to improvements following anodal tDCS (AtDCS), with 69% of studies (n = 11) investigating this core component of physical fitness reporting positive effects. The primary motor cortex and dorsolateral prefrontal cortex were targeted the most, with positive results being reported on muscle and cardiopulmonary endurance. Finally, online tDCS seemed most beneficial, and no clear relationship between tDCS and dose-related parameters seemed present. These findings can contribute to optimizing tDCS interventions during the rehabilitation of patients with a variety of (chronic) diseases such as cardiovascular disease. Therefore, future studies should focus on further unraveling the potential of AtDCS on physical fitness and, more specifically, muscle endurance in both healthy subjects and patients suffering from (chronic) diseases. This study was registered in Prospero with the registration number CRD42021258529. "To enable PROSPERO to focus on COVID-19 registrations during the 2020 pandemic, this registration record was automatically published exactly as submitted. The PROSPERO team has not checked eligibility".

Transcranial Direct Current Stimulation (Tdcs) for Post- Stroke Anxiety and Depression Following Sars-Cov2 Infection and Neurocovid-19 Contraction

Background: Transcranial direct current stimulation (tDCS) is effective in the man-agement of patients with depression and anxiety. However, it is not known if it is effective in the case of anxiety and depression following SARS-CoV2 and NeuroCOVID-19 infection. The aim of this study was to determine the efficacy of stimulating the brain with the use of a tDCS protocol ameliorated by a functional neuromarker, and here based on HBI methodology to reduce anxiety and depression following SARS-CoV2 infection and NeuroCOVID-19 contraction.Case study: A 47-year-old patient manifested severe anxiety and depression following a stroke following SARS-CoV2 infection and Neuro-COVID-19 contraction. The anxiety and depression were diagnosed using the HAD-Scale (Zigmond, Snaith 1983). A score of 8 to 10 is broad ly accepted as indicating mild symptoms, a score between 11-16 suggests moderate anxiety or depression, and a score of 16 or more indicates severe anxiety or depressive symptoms. The patient received anodal tDCS to the left DLPFC using two different applica-tion protocols. Initially, a stimulation session of 2 milliamperes (mA) intensity for 20 minutes was administered every working day for 2 weeks. After 3 weeks, she subsequently received 7 daily sessions of periodic stimulations of an intensity of 2 mA for 13 minutes each with 20 minutes inter-session intervals for 1 week. It was found that tDCS delivered via the dorsolateral prefrontal cortex (DLPFC) was effective in the reduction of post-stroke anxiety and depression following SARS-CoV2 infection and NeuroCOVID-19 contraction. Immediately follow-ing the final session of the initial protocol of stimulation, the Had Score was reduced for anxiety from 18 to 6 points, and for depression from 17 to 5 points and the symptoms disappeared.Conclusions: The HBI methodology allowed for the detection of a functional neu-romarker of anxiety and depression and the development of a tDCS protocol. It was found that tDCS delivered via the dorsolateral pre-frontal cortex (DLPFC) was effective in the reduction of post-stroke anxiety and depression following SARS-CoV2 infection and Neu-roCOVID-19 contraction.

Using Remotely Supervised At-Home TES for Enhancing Mental Resilience.

We are in the midst of a mental health crisis with major depressive disorder being the most prevalent among mental health disorders and up to 30% of patients not responding to first-line treatments. Noninvasive Brain Stimulation (NIBS) techniques have proven to be effective in treating depression. However, there is a fundamental problem of scale. Currently, any type of NIBS treatment requires patients to repeatedly visit a clinic to receive brain stimulation by trained personnel. This is an often-insurmountable barrier to both patients and healthcare providers in terms of time and cost. In this perspective, we assess to what extent Transcranial Electrical Stimulation (TES) might be administered with remote supervision in order to address this scaling problem and enable neuroenhancement of mental resilience at home. Social, ethical, and technical challenges relating to hardware- and software-based solutions are discussed alongside the risks of stimulation under- or over-use. Solutions to provide users with a safe and transparent ongoing assessment of aptitude, tolerability, compliance, and/or misuse are proposed, including standardized training, eligibility screening, as well as compliance and side effects monitoring. Looking into the future, such neuroenhancement could be linked to prevention systems which combine home-use TES with digital sensor and mental monitoring technology to index decline in mental wellbeing and avoid relapse. Despite the described social, ethical legal, and technical challenges, the combination of remotely supervised, at-home TES setups with dedicated artificial intelligence systems could be a powerful weapon to combat the mental health crisis by bringing personalized medicine into people's homes.

Tele-tDCS: A Novel Tele-neuromodulation Framework using Internet of Medical Things

As part of the Internet of Medical Things (IoMT) within Biomedical Engineering, telehealth is an emerging field. Due to the recent events surrounding COVID-19, it has become obvious that Telehealth treatments must be developed as a means of protecting vulnerable patients in hospitals by reducing the need to visit and therefore reducing risk to physicians. This paper investigates the feasibility of developing a non-invasive remote neuro-stimulation system using internet-based transcranial Direct Current Stimulation (tDCS). A hardware-based prototype tDCS device has been developed to be controlled using a remote command-line interface over the internet. As a result, a physician can remotely set the parameters for the tDCS treatment and monitor the treatment in real-time to ensure patient safety. In this study, the feasibility of a Tele-tDCS system was investigated, as well as the capabilities a Tele-tDCS system should offer to patients.

Personal Protective Equipment Alters Leg Muscle Fatigability Independent of Transcranial Direct Current Stimulation: A Comparison with Pre-COVID-19 Pandemic Results.

In response to the COVID-19 pandemic, the use of personal protective equipment (PPE; e.g., face mask) has increased. Mandating subjects to wear PPE during vigorous exercise might affect the fatigue outcomes of transcranial direct current stimulation (tDCS) studies. The purpose of this study was to investigate whether the use of PPE affected the performance of a tDCS-influenced fatigue task in healthy adults. A total of 16 young and healthy subjects were recruited and wore PPE during an isokinetic fatigue task in conjunction with sham, 2 mA, and 4 mA tDCS conditions. Subjects were matched to subjects who did not wear PPE during our previous pre-pandemic study in which right knee extensor fatigability increased under these same conditions. The results show that right knee extensor fatigability, derived from torque and work (FI-T and FI-W, respectively), was higher in the PPE study compared to the No PPE study in the sham condition. Additionally, there were no differences in knee extensor fatigability or muscle activity between sham, 2 mA, and 4 mA tDCS in the present study, which contrasts with our previous results. Thus, PPE worn by subjects and researchers might have a detrimental effect on fatigue outcomes in tDCS studies irrespective of the stimulation intervention.

Editorial for special issue on neglect rehabilitation.

It is clear already that in current and future years more people will suffer from stroke, whether related to COVID-19 or not, and given its prevalence, many more people's lives will be affected by neglect. Here we hope to have contributed to its possible amelioration with highlights of the latest thinking on neglect diagnosis, prevalence and treatment.

Applications of Non-invasive Neuromodulation for the Management of Disorders Related to COVID-19.

Background: Novel coronavirus disease (COVID-19) morbidity is not restricted to the respiratory system, but also affects the nervous system. Non-invasive neuromodulation may be useful in the treatment of the disorders associated with COVID-19. Objective: To describe the rationale and empirical basis of the use of non-invasive neuromodulation in the management of patients with COVID-10 and related disorders. Methods: We summarize COVID-19 pathophysiology with emphasis of direct neuroinvasiveness, neuroimmune response and inflammation, autonomic balance and neurological, musculoskeletal and neuropsychiatric sequela. This supports the development of a framework for advancing applications of non-invasive neuromodulation in the management COVID-19 and related disorders. Results: Non-invasive neuromodulation may manage disorders associated with COVID-19 through four pathways: (1) Direct infection mitigation through the stimulation of regions involved in the regulation of systemic anti-inflammatory responses and/or autonomic responses and prevention of neuroinflammation and recovery of respiration; (2) Amelioration of COVID-19 symptoms of musculoskeletal pain and systemic fatigue; (3) Augmenting cognitive and physical rehabilitation following critical illness; and (4) Treating outbreak-related mental distress including neurological and psychiatric disorders exacerbated by surrounding psychosocial stressors related to COVID-19. The selection of the appropriate techniques will depend on the identified target treatment pathway. Conclusion: COVID-19 infection results in a myriad of acute and chronic symptoms, both directly associated with respiratory distress (e.g., rehabilitation) or of yet-to-be-determined etiology (e.g., fatigue). Non-invasive neuromodulation is a toolbox of techniques that based on targeted pathways and empirical evidence (largely in non-COVID-19 patients) can be investigated in the management of patients with COVID-19.

Update on the Use of Transcranial Electrical Brain Stimulation to Manage Acute and Chronic COVID-19 Symptoms.

The coronavirus disease 19 (COVID-19) pandemic has resulted in the urgent need to develop and deploy treatment approaches that can minimize mortality and morbidity. As infection, resulting illness, and the often prolonged recovery period continue to be characterized, therapeutic roles for transcranial electrical stimulation (tES) have emerged as promising non-pharmacological interventions. tES techniques have established therapeutic potential for managing a range of conditions relevant to COVID-19 illness and recovery, and may further be relevant for the general management of increased mental health problems during this time. Furthermore, these tES techniques can be inexpensive, portable, and allow for trained self-administration. Here, we summarize the rationale for using tES techniques, specifically transcranial Direct Current Stimulation (tDCS), across the COVID-19 clinical course, and index ongoing efforts to evaluate the inclusion of tES optimal clinical care.

Randomized Controlled Study Evaluating Efficiency of Low Intensity Transcranial Direct Current Stimulation (tDCS) for Dyspnea Relief in Mechanically Ventilated COVID-19 Patients in ICU: The tDCS-DYSP-COVID Protocol.

The severe respiratory distress syndrome linked to the new coronavirus disease (COVID-19) includes unbearable dyspneic suffering which contributes to the deterioration of the prognosis of patients in intensive care unit (ICU). Patients are put on mechanical ventilation to reduce respiratory suffering and preserve life. Despite this mechanical ventilation, most patients continue to suffer from dyspnea. Dyspnea is a major source of suffering in intensive care and one of the main factors that affect the prognosis of patients. The development of innovative methods for its management, especially non-drug management is more than necessary. In recent years, numerous studies have shown that transcranial direct current stimulation (tDCS) could modulate the perception of acute or chronic pain. In the other hand, it has been shown that the brain zones activated during pain and dyspnea are close and/or superimposed, suggesting that brain structures involved in the integration of aversive emotional component are shared by these two complex sensory experiences. Therefore, it can be hypothesized that stimulation by tDCS with regard to the areas which, in the case of pain have activated one or more of these brain structures, may also have an effect on dyspnea. In addition, our team recently demonstrated that the application of tDCS on the primary cortical motor area can modulate the excitability of the respiratory neurological pathways. Indeed, tDCS in anodal or cathodal modality reduced the excitability of the diaphragmatic cortico-spinal pathways in healthy subjects. We therefore hypothesized that tDCS could relieve dyspnea in COVID-19 patients under mechanical ventilation in ICU. This study was designed to evaluate effects of two modalities of tDCS (anodal and cathodal) vs. placebo, on the relief of dyspnea in COVID-19 patients requiring mechanical ventilation in ICU. Trial Registration: This protocol is derived from the tDCS-DYSP-REA project registered on ClinicalTrials.gov NCT03640455. It will however be registered under its own NCT number.