Publications by authors named "Marom Bikson"

278 Publications

Neuromodulation Strategies to Reduce Inflammation and Improve Lung Complications in COVID-19 Patients.

Front Neurol 2022 14;13:897124. Epub 2022 Jul 14.

Department of Neurology, Ghent University Hospital, Ghent, Belgium.

Since the outbreak of the COVID-19 pandemic, races across academia and industry have been initiated to identify and develop disease modifying or preventative therapeutic strategies has been initiated. The primary focus has been on pharmacological treatment of the immune and respiratory system and the development of a vaccine. The hyperinflammatory state ("cytokine storm") observed in many cases of COVID-19 indicates a prognostically negative disease progression that may lead to respiratory distress, multiple organ failure, shock, and death. Many critically ill patients continue to be at risk for significant, long-lasting morbidity or mortality. The human immune and respiratory systems are heavily regulated by the central nervous system, and intervention in the signaling of these neural pathways may permit targeted therapeutic control of excessive inflammation and pulmonary bronchoconstriction. Several technologies, both invasive and non-invasive, are available and approved for clinical use, but have not been extensively studied in treatment of the cytokine storm in COVID-19 patients. This manuscript provides an overview of the role of the nervous system in inflammation and respiration, the current understanding of neuromodulatory techniques from preclinical and clinical studies and provides a rationale for testing non-invasive neuromodulation to modulate acute systemic inflammation and respiratory dysfunction caused by SARS-CoV-2 and potentially other pathogens. The authors of this manuscript have co-founded the International Consortium on Neuromodulation for COVID-19 to advocate for and support studies of these technologies in the current coronavirus pandemic.
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http://dx.doi.org/10.3389/fneur.2022.897124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329660PMC
July 2022

Potential of Transcranial Direct Current Stimulation in Alzheimer's Disease: Optimizing Trials Toward Clinical Use.

J Clin Neurol 2022 Jul;18(4):391-400

Department of Psychiatry and Behavioral Health, Stony Brook University Renaissance School of Medicine, Stony Brook, NY, USA.

Transcranial direct current stimulation (tDCS) is a safe and well-tolerated noninvasive method for stimulating the brain that is rapidly developing into a treatment method for various neurological and psychiatric conditions. In particular, there is growing evidence of a therapeutic role for tDCS in ameliorating or delaying the cognitive decline in Alzheimer's disease (AD). We provide a brief overview of the current development and application status of tDCS as a nonpharmacological therapeutic method for AD and mild cognitive impairment (MCI), summarize the levels of evidence, and identify the improvements needed for clinical applications. We also suggest future directions for large-scale controlled clinical trials of tDCS in AD and MCI, and emphasize the necessity of identifying the mechanistic targets to facilitate clinical applications.
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http://dx.doi.org/10.3988/jcn.2022.18.4.391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9262447PMC
July 2022

Middle cerebral artery blood flow stability in response to high-definition transcranial electrical stimulation: A randomized sham-controlled clinical trial.

Clin Neurol Neurosurg 2022 Jun 20;220:107345. Epub 2022 Jun 20.

Department of Neurosciences and Behavioral Sciences, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil. Electronic address:

Since neuronal activity is coupled with neurovascular activity, we aimed to analyze the cerebral blood flow hemodynamics during and following high-definition transcranial direct current stimulation (HD-tDCS). We assessed the mean middle cerebral artery blood flow velocity (MCA-BFv) bilaterally using transcranial doppler ultrasound, during and after HD-tDCS, in eleven right-handed healthy adult participants (6 women, 5 men; mean age 31 ± 5.6 years old), with no evidence of brain or cardiovascular dysfunction. The HD-tDCS electrode montage was centered over the right temporo-parietal junction. The stimulation protocol comprised 3 blocks of 2 min at each current intensity (1, 2, and 3 mA) and an inter-stimulus interval of 5 min between blocks. Participants received three electrical stimulation conditions (anode center, cathode center, and sham) on three different days, with an interval of at least 24 h. Stimulation was well tolerated across HD-tDCS conditions tested, and the volunteers reported no significant discomfort related to stimulation. There was no significant difference in the right or the left MCA-BFv during or after the stimulation protocol across all stimulation conditions. We conclude that at a range of intensities, vascular reaction assessed using middle cerebral artery blood flow is not significantly altered during or after HD-tDCS both locally and remotely, which provides further evidence for the safety of HD-tDCS.
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http://dx.doi.org/10.1016/j.clineuro.2022.107345DOI Listing
June 2022

Computational Modeling of Deep Tissue Heating by an Automatic Thermal Massage Bed: Predicting the Effects on Circulation.

Front Med Technol 2022 14;4:925554. Epub 2022 Jun 14.

Department of Biomedical Engineering, City College of New York, New York, NY, United States.

Automatic thermal and mechanical massage beds support self-managed treatment, including reduction of pain and stress, enhanced circulation, and improved mobility. As the devices become more sophisticated (increasing the degrees of freedom), it is essential to identify the settings that best target the desired tissue. To that end, we developed an MRI-derived model of the lower back and simulated the physiological effects of a commercial thermal-mechanical massage bed. Here we specifically estimated the tissue temperature and increased circulation under steady-state conditions for typical thermal actuator settings (i.e., 45-65°C). Energy transfer across nine tissues was simulated with finite element modeling (FEM) and the resulting heating was coupled to blood flow with an empirically-guided model of temperature-dependent circulation. Our findings indicate that thermal massage increases tissue temperature by 3-8°C and 1-3°C at depths of 2 and 3 cm, respectively. Importantly, due to the rapid (non-linear) increase of circulation with local temperature, this is expected to increase blood flow four-fold (4x) at depths occupied by deep tissue and muscle. These predictions are consistent with prior clinical observations of therapeutic benefits derived from spinal thermal massage.
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http://dx.doi.org/10.3389/fmedt.2022.925554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9238293PMC
June 2022

Transcranial direct current stimulation during a prolonged cognitive task: the effect on cognitive and shooting performances in professional female basketball players.

Ergonomics 2022 Jul 11:1-14. Epub 2022 Jul 11.

Center of Mathematics, Computation, and Cognition, Universidade Federal do ABC, São Bernardo do Campo, Brazil.

The negative effect of prolonged cognitive demands on psychomotor skills in athletes has been demonstrated. Transcranial direct current stimulation (tDCS) could be used to mitigate this effect. This study examined the effects of tDCS over the left dorsolateral prefrontal cortex (DLPFC) during a 30-min inhibitory Stroop task on cognitive and shooting performances of professional female basketball players. Following a randomised, double-blinded, sham-controlled, cross-over design, players were assigned to receive anodal tDCS (a-tDCS, 2 mA for 20 min) or sham-tDCS in two different sessions. Data from 8 players were retained for analysis. Response Time decreased significantly over time ( < 0.001; partial = 0.44; no effect of condition, or condition vs. time interaction). No difference in mean accuracy and shooting performance was observed between tDCS conditions. The results suggest that a-tDCS exert no additional benefits in reducing the negative effects of prolonged cognitive demands on technical performance compared to sham (placebo). Prolonged cognitive demands can negatively affect the athletes' performance. We tested whether transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (DLPFC) could attenuate these effects on cognitive and shooting performance in professional female basketball players. However, tDCS did not exert any additional benefits compared to sham. tDCS: transcranial direct current stimulation; a-tDCS: anodal transcranial direct current stimulation; PFC: prefrontal cortex; DLPFC: dorsolateral prefrontal cortex; PCT: prolonged cognitive task; TT: time trial; RT: response time; NASA-TLX: National Aeronautics and Space Administration Task Load Index; RPE: ratings of perceived exertion; CR-10 scale: category rating scale; EEG: electroencephalogram; AU: arbitrary units.
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http://dx.doi.org/10.1080/00140139.2022.2096262DOI Listing
July 2022

A pilot randomized controlled trial of supervised, at-home, self-administered transcutaneous auricular vagus nerve stimulation (taVNS) to manage long COVID symptoms.

Res Sq 2022 Jun 21. Epub 2022 Jun 21.

Background Although the coronavirus disease 19 (COVID-19) pandemic has now impacted the world for over two years, the persistent secondary neuropsychiatric effects are still not fully understood. These "long COVID" symptoms, also referred to as post-acute sequelae of SARS-CoV-2 infection (PASC), can persist for months after infection without any effective treatments. Long COVID involves a complex heterogenous symptomology and can lead to disability and limit work. Long COVID symptoms may be due to sustained inflammatory responses and prolonged immune response after infection. Interestingly, vagus nerve stimulation (VNS) may have anti-inflammatory effects, however, until recently, VNS could not be self-administered, at-home, noninvasively. Methods We created a double-blind, noninvasive transcutaneous auricular VNS (taVNS) system that can be self-administered at home with simultaneous remote monitoring of physiological biomarkers and video supervision by study staff. Subsequently, we carried out a pilot (n = 13) randomized, sham-controlled, trial with this system for four weeks to treat nine predefined long covid symptoms (anxiety, depression, vertigo, anosmia, ageusia, headaches, fatigue, irritability, brain fog). No in-person patient contact was needed, with informed consent, trainings, ratings, and all procedures being conducted remotely during the pandemic (2020-2021) and equipment being shipped to individuals' homes. This trial was registered onClinicalTrials.gov under the identifier: NCT04638673. Results Four-weeks of at-home self-administered taVNS (two, one-hour sessions daily, delivered at suprathreshold intensities) was feasible and safe. Although our trial was not powered to determine efficacy as an intervention in a heterogenous population, the trends in the data suggest taVNS may have a mild to moderate effect in reducing mental fatigue symptoms in a subset of individuals. This innovative study demonstrates the safety and feasibility of supervised self-administered taVNS under a fully contactless protocol and suggests that future studies can safely investigate this novel form of brain stimulation at-home for a variety of neuropsychiatric and motor recovery applications.
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http://dx.doi.org/10.21203/rs.3.rs-1716096/v1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9238186PMC
June 2022

Transcranial Electrical Stimulation for Psychiatric Disorders in Adults: A Primer.

Focus (Am Psychiatr Publ) 2022 Jan 25;20(1):19-31. Epub 2022 Jan 25.

Department of Psychology, Graduate Center, and Department of Psychology, Hunter College, City University of New York, New York City (Cho, Dennis-Tiwary); Department and Institute of Psychiatry and Service of Interdisciplinary Neuromodulation, Faculty of Medicine, University of São Paulo, São Paulo, Brazil (Razza, Borrione, Brunoni, Sudbrack-Oliveira); Department of Biomedical Engineering, City College of New York, City University of New York, New York City (Bikson); Department of Neurology, Grossman School of Medicine, New York University, New York City (Charvet); Department of Internal Medicine, Faculty of Medicine, University of São Paulo, and University Hospital, University of São Paulo, São Paulo, Brazil (Brunoni).

Transcranial electrical stimulation (tES) comprises noninvasive neuromodulation techniques that deliver low-amplitude electrical currents to targeted brain regions with the goal of modifying neural activities. Expanding evidence from the past decade, specifically using transcranial direct current simulation and transcranial alternating current stimulation, presents promising applications of tES as a treatment for psychiatric disorders. In this review, the authors discuss the basic technical aspects and mechanisms of action of tES in the context of clinical research and practice and review available evidence for its clinical use, efficacy, and safety. They also review recent advancements in use of tES for the treatment of depressive disorders, schizophrenia, substance use disorders, and obsessive-compulsive disorder. Findings largely support growing evidence for the safety and efficacy of tES in the treatment of patients with resistance to existing treatment options, particularly demonstrating promising treatment outcomes for depressive disorders. Future directions of tES research for optimal application in clinical settings are discussed, including the growing home-based, patient-friendly methods and the potential pairing with existing pharmacological or psychotherapeutic treatments for enhanced outcomes. Finally, neuroimaging advancements may provide more specific mapping of brain networks, aiming at more precise tES therapeutic targeting in the treatment of psychiatric disorders.
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http://dx.doi.org/10.1176/appi.focus.20210020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9063596PMC
January 2022

Stance Phase Gait Training Post Stroke Using Simultaneous Transcranial Direct Current Stimulation and Motor Learning-Based Virtual Reality-Assisted Therapy: Protocol Development and Initial Testing.

Brain Sci 2022 May 28;12(6). Epub 2022 May 28.

VA Northeast Ohio Healthcare System, Cleveland, OH 44106, USA.

Gait deficits are often persistent after stroke, and current rehabilitation methods do not restore normal gait for everyone. Targeted methods of focused gait therapy that meet the individual needs of each stroke survivor are needed. Our objective was to develop and test a combination protocol of simultaneous brain stimulation and focused stance phase training for people with chronic stroke (>6 months). We combined Transcranial Direct Current Stimulation (tDCS) with targeted stance phase therapy using Virtual Reality (VR)-assisted treadmill training and overground practice. The training was guided by motor learning principles. Five users (>6 months post-stroke with stance phase gait deficits) completed 10 treatment sessions. Each session began with 30 min of VR-assisted treadmill training designed to apply motor learning (ML)-based stance phase targeted practice. During the first 15 min of the treadmill training, bihemispheric tDCS was simultaneously delivered. Immediately after, users completed 30 min of overground (ML)-based gait training. The outcomes included the feasibility of protocol administration, gait speed, Timed Up and Go (TUG), Functional Gait Assessment (FGA), paretic limb stance phase control capability, and the Fugl-Meyer for lower extremity coordination (FM). The changes in the outcome measures (except the assessments of stance phase control capability) were calculated as the difference from baseline. Statistically and clinically significant improvements were observed after 10 treatment sessions in gait speed (0.25 ± 0.11 m/s) and FGA (4.55 ± 3.08 points). Statistically significant improvements were observed in TUG (2.36 ± 3.81 s) and FM (4.08 ± 1.82 points). A 10-session intervention combining tDCS and ML-based task-specific gait rehabilitation was feasible and produced clinically meaningful improvements in lower limb function in people with chronic gait deficits after stroke. Because only five users tested the new protocol, the results cannot be generalized to the whole population. As a contribution to the field, we developed and tested a protocol combining brain stimulation and ML-based stance phase training for individuals with chronic stance phase deficits after stroke. The protocol was feasible to administer; statistically and/or clinically significant improvements in gait function across an array of gait performance measures were observed with this relatively short treatment protocol.
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http://dx.doi.org/10.3390/brainsci12060701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9221094PMC
May 2022

Non-invasive brain stimulation and neuroenhancement.

Clin Neurophysiol Pract 2022 25;7:146-165. Epub 2022 May 25.

Department of Medical Ethics and Health Policy, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.

Attempts to enhance human memory and learning ability have a long tradition in science. This topic has recently gained substantial attention because of the increasing percentage of older individuals worldwide and the predicted rise of age-associated cognitive decline in brain functions. Transcranial brain stimulation methods, such as transcranial magnetic (TMS) and transcranial electric (tES) stimulation, have been extensively used in an effort to improve cognitive functions in humans. Here we summarize the available data on low-intensity tES for this purpose, in comparison to repetitive TMS and some pharmacological agents, such as caffeine and nicotine. There is no single area in the brain stimulation field in which only positive outcomes have been reported. For self-directed tES devices, how to restrict variability with regard to efficacy is an essential aspect of device design and function. As with any technique, reproducible outcomes depend on the equipment and how well this is matched to the experience and skill of the operator. For self-administered non-invasive brain stimulation, this requires device designs that rigorously incorporate human operator factors. The wide parameter space of non-invasive brain stimulation, including dose (e.g., duration, intensity (current density), number of repetitions), inclusion/exclusion (e.g., subject's age), and homeostatic effects, administration of tasks before and during stimulation, and, most importantly, placebo or nocebo effects, have to be taken into account. The outcomes of stimulation are expected to depend on these parameters and should be strictly controlled. The consensus among experts is that low-intensity tES is safe as long as tested and accepted protocols (including, for example, dose, inclusion/exclusion) are followed and devices are used which follow established engineering risk-management procedures. Devices and protocols that allow stimulation outside these parameters cannot claim to be "safe" where they are applying stimulation beyond that examined in published studies that also investigated potential side effects. Brain stimulation devices marketed for consumer use are distinct from medical devices because they do not make medical claims and are therefore not necessarily subject to the same level of regulation as medical devices (i.e., by government agencies tasked with regulating medical devices). Manufacturers must follow ethical and best practices in marketing tES stimulators, including not misleading users by referencing effects from human trials using devices and protocols not similar to theirs.
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http://dx.doi.org/10.1016/j.cnp.2022.05.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9207555PMC
May 2022

Transcranial Direct Current Stimulation (tDCS): Pain Management in End-Stage Renal Disease - Report of an Early Randomized Controlled Trial.

J Pain Symptom Manage 2022 May 28. Epub 2022 May 28.

Department of Medicine (Nephrology) (G.M.K.), Federal University of Sao Paulo, São Paulo, Brazil.

Context: Chronic pain in end-stage renal disease (ESRD) is an increasingly neglected clinical problem affecting more than 60% of patients. Long-term chronic pain could be associated with brain imbalance in circuits of pain matrix and is associated with poor quality of life (QoL) and mood disturbance.

Objectives: The aim of this study was evaluating the effects of transcranial direct current stimulation (tDCS) on pain, QoL, depression, anxiety and affectivity in ESRD patients undergoing hemodialysis (HD).

Methods: This double-blind, randomized, sham-controlled trial included 30 patients with chronic pain undergoing HD. Participants were allocated to Active tDCS and Sham tDCS and received ten non-consecutive sessions of anodal motor cortex stimulation (M1/Sp2 montage) at 2 mA intensity for 20 min. The primary outcome was pain assessed using numeric rating scale (NRS) and collected at baseline, immediately after the 10th day of intervention, one week, two weeks, and four weeks after the last stimulation. Secondary outcomes included QoL, depression, anxiety and affectivity collected before and after intervention.

Results: A mixed ANOVA model showed significant interaction between group and time on pain F(4.112) = 3.106, P = 0.01 with main effects of group (P = 0.03). Before and after intervention, a significant improvement was observed in QoL (P = 0.009), general health (P = 0.03), fatigue (P = 0.05), symptoms (P = 0.05) depression (P = 0.01) and anxiety (P = 0.01). No difference was found for affectivity.

Conclusion: Anodal tDCS over the motor cortex emerges as a potential therapeutic approach for improving pain, QoL, and mood in patients with ESRD.
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http://dx.doi.org/10.1016/j.jpainsymman.2022.05.018DOI Listing
May 2022

Efficacy and safety of HD-tDCS and respiratory rehabilitation for critically ill patients with COVID-19 The HD-RECOVERY randomized clinical trial.

Brain Stimul 2022 May-Jun;15(3):780-788. Epub 2022 May 11.

Department of Biomedical Engineering, The City College of New York of CUNY, New York, United States.

Background And Purpose: Acute Respiratory Distress Syndrome (ADRS) due to coronavirus disease 2019 (COVID-19) has been associated with muscle fatigue, corticospinal pathways dysfunction, and mortality. High-Definition transcranial Direct Current Stimulation (HD-tDCS) may be used to attenuate clinical impairment in these patients. The HD-RECOVERY randomized clinical trial was conducted to evaluate the efficacy and safety of HD-tDCS with respiratory rehabilitation in patients with moderate to severe ARDS due to COVID-19.

Methods: Fifty-six critically ill patients were randomized 1:1 to active (n = 28) or sham (n = 28) HD-tDCS (twice a day, 30-min, 3-mA) plus respiratory rehabilitation for up to 10 days or until intensive care unit discharge. The primary outcome was ventilator-free days during the first 28 days, defined as the number of days free from mechanical ventilation. Furthermore, secondary outcomes such as delirium, organ failure, hospital length of stay and adverse effects were investigated.

Results: Active HD-tDCS induced more ventilator-free days compared to sham HD-tDCS. Patients in the active group vs in the sham group experienced lower organ dysfunction, delirium, and length of stay rates over time. In addition, positive clinical response was higher in the active vs sham group. There was no significant difference in the prespecified secondary outcomes at 5 days. Adverse events were similar between groups.

Conclusions: Among patients with COVID-19 and moderate to severe ARDS, use of active HD-tDCS compared with sham HD-tDCS plus respiratory rehabilitation resulted in a statistically significant increase in the number of ventilator-free days over 28 days. HD-tDCS combined with concurrent rehabilitation therapy is a safe, feasible, potentially add-on intervention, and further trials should examine HD-tDCS efficacy in a larger sample of patients with COVID-19 and severe hypoxemia.
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http://dx.doi.org/10.1016/j.brs.2022.05.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9093082PMC
May 2022

Tolerability and feasibility of at-home remotely supervised transcranial direct current stimulation (RS-tDCS): Single-center evidence from 6,779 sessions.

Brain Stimul 2022 May-Jun;15(3):707-716. Epub 2022 Apr 22.

Department of Neurology, NYU Grossman School of Medicine, New York, NY, USA. Electronic address:

Introduction: The ability to deploy transcranial direct current stimulation (tDCS) at home is a key usability advantage to support scaling for pivotal clinical trials. We have established a home-based tDCS protocol for use in clinical trials termed remotely supervised (RS)-tDCS.

Objective: To report the tolerability and feasibility of tDCS sessions completed to date using RS-tDCS in clinical trials.

Methods: We analyzed tolerability (i.e., adverse events, AEs) reported in six Class I/II/III trials using RS-tDCS to study symptom outcomes over 10 to 60 daily applications. Across the six clinical trials, 308 participants (18-78 years old) completed an average of 23 sessions for a total of 6779 RS-tDCS administrations. The majority of participants were diagnosed with multiple sclerosis, and open-label trials included those diagnosed with a range of other conditions (e.g., Parkinson's disease, post-stroke aphasia, traumatic brain injury, cerebellar ataxia), with minimum-to-severe neurologic disability. Clinical trial feasibility (i.e., treatment fidelity and blinding integrity) was examined using two Class I randomized controlled trials (RCTs).

Results: No serious AEs occurred. Across administrations, three sessions (0.04%) were aborted due to discomfort, but no participant discontinued due to tolerability. The AEs most commonly reported by participants were tingling (68%), itching (41%) and warmth sensation (42%) at the electrode site, and these were equally reported in active and sham tDCS conditions. The two Class I RCTs resulted in rapid enrollment, high fidelity to treatment completion, and blinding integrity.

Conclusions: At-home RS-tDCS is tolerable, including when used over extended periods of time. Home-based RS-tDCS is feasible and can enable Class I tDCS clinical trial designs.
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http://dx.doi.org/10.1016/j.brs.2022.04.014DOI Listing
June 2022

Selective augmentation of corticospinal motor drive with trans-spinal direct current stimulation in the cat.

Brain Stimul 2022 May-Jun;15(3):624-634. Epub 2022 Mar 31.

Department of Molecular, Cellular and Biomedical Sciences, CUNY School of Medicine, New York, NY, USA; The Graduate Center, City University of New York, NY, USA. Electronic address:

Background: A key outcome for spinal cord stimulation for neurorehabilitation after injury is to strengthen corticospinal system control of the arm and hand. Non-invasive, compared with invasive, spinal stimulation minimizes risk but depends on muscle-specific actions for restorative functions.

Objective: We developed a large-animal (cat) model, combining computational and experimental techniques, to characterize neuromodulation with transcutaneous spinal direct current stimulation (tsDCS) for facilitation of corticospinal motor drive to specific forelimb muscles.

Methods: Acute modulation of corticospinal function by tsDCS was measured using motor cortex-evoked muscle potentials (MEPs). The effects of current intensity, polarity (cathodal, anodal), and electrode position on specific forelimb muscle (biceps vs extensor carpi radialis, ECR) MEP modulation were examined. Locations of a key target, the motoneuron pools, were determined using neuronal tracing. A high-resolution anatomical (MRI and CT) model was developed for computational simulation of spinal current flow during tsDCS.

Results: Effects of tsDCS on corticospinal excitability were robust and immediate, therefore supporting MEPs as a sensitive marker of tsDCS targeting. Varying cathodal/anodal current intensity modulated MEP enhancement/suppression, with higher cathodal sensitivity. Muscle-specificity depended on cathode position; the rostral position preferentially augmented biceps responses and the caudal position, ECR responses. Precise anatomical current-flow modeling, supplemented with target motor pool distributions, can explain tsDCS focality on muscle groups.

Conclusion: Anatomical current-flow modeling with physiological validation based on MEPs provides a framework to optimize muscle-specific tsDCS interventions. tsDCS targeting of representative motor pools enables muscle- and response-specific neuromodulation of corticospinal motor drive.
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http://dx.doi.org/10.1016/j.brs.2022.03.007DOI Listing
March 2022

Evaluation of the effect of transcranial direct current stimulation on language impairments in the behavioural variant of frontotemporal dementia.

Brain Commun 2022 29;4(2):fcac050. Epub 2022 Mar 29.

Groupe de Dynamiques Cérébrales, Plasticité et Rééducation, FRONTLAB team, Institut du Cerveau et de la Moelle Epinière, CNRS UMR 7225, INSERM 1127, Sorbonne Université, Paris, France.

The behavioural variant of frontotemporal dementia is a neurodegenerative disease characterized by bilateral atrophy of the prefrontal cortex, gradual deterioration of behavioural and executive capacities, a breakdown of language initiation and impaired search mechanisms in the lexicon. To date, only a few studies have analysed the modulation of language deficits in the behavioural variant of frontotemporal dementia patients with transcranial direct current stimulation, yet with inconsistent results. Our goal was to assess the impact on language performance of a single session of transcranial direct current stimulation on patients with the behavioural variant of frontotemporal dementia. Using a sham-controlled double-blind crossover design in a cohort of behavioural frontotemporal dementia patients ( = 12), we explored the impact on language performance of a single transcranial direct current stimulation session delivering anodal or cathodal transcranial direct current stimulation, over the left and right dorsolateral prefrontal cortex, compared with sham stimulation. A and a task were performed prior and following transcranial direct current stimulation, to assess modulatory effects on language. Behavioural frontotemporal dementia patients were impaired in all evaluation tasks at baseline compared with healthy controls. Computational finite element method (FEM) models of cortical field distribution corroborated expected impacts of left-anodal and right-cathodal transcranial direct current stimulation over the dorsolateral prefrontal cortex and showed lower radial field strength in case of atrophy. However, none of the two tasks showed statistically significant evidence of language improvement caused by active transcranial direct current stimulation compared with sham. Our findings do not argue in favour of pre-therapeutic effects and suggest that stimulation strategies evaluating the modulatory role of transcranial direct current stimulation in the behavioural variant of frontotemporal dementia must carefully weigh the influence of symptom severity and cortical atrophy affecting prefrontal regions to ensure clinical success.
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http://dx.doi.org/10.1093/braincomms/fcac050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8963324PMC
March 2022

Development and Clinical Validation of a Finite Element Method Model Mapping Focal Intracranial Cooling.

IEEE Trans Neural Syst Rehabil Eng 2022 Mar 22;PP. Epub 2022 Mar 22.

Therapeutic hypothermia (TH) is a common and effective technique to reduce inflammation and induce neuroprotection across a variety of diseases. Focal TH of the brain can avoid the side effects of systemic cooling. The degree and extent of focal TH are a function of cooling probe design and local brain thermoregulation processes. To refine focal TH probe design, with application-specific optimization, we develop precise computational models of brain thermodynamics under intense local cooling. Here, we present a novel multiphysics in silico model that can accurately predict brain response to focal cooling. The model was parameterized from previously described values of metabolic activity, thermal conductivity, and temperature-dependent cerebral perfusion. The model was validated experimentally using data from clinical cases where local cooling was induced intracranially and brain temperatures monitored in real-time with MR thermometry. The validated model was then used to identify optimal design probe parameters to maximize volumetric TH, including considering three stratifications of cooling (mild, moderate, and profound) to produce Volume of Tissue Cooled (VOTC) maps. We report cooling radius increases in a nearly linear fashion with probe length and decreasing probe surface temperature.
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http://dx.doi.org/10.1109/TNSRE.2022.3161085DOI Listing
March 2022

The Concept, Development, and Application of a Home-Based High-Definition tDCS for Bilateral Motor Cortex Modulation in Migraine and Pain.

Front Pain Res (Lausanne) 2022 7;3:798056. Epub 2022 Feb 7.

Neural Engineering Laboratory, Department of Biomedical Engineering, The City College of New York, New York, NY, United States.

Whereas, many debilitating chronic pain disorders are dominantly bilateral (e.g., fibromyalgia, chronic migraine), non-invasive and invasive cortical neuromodulation therapies predominantly apply unilateral stimulation. The development of excitatory stimulation targeting bilateral primary motor (M1) cortices could potentially expand its therapeutic effect to more global pain relief. However, this is hampered by increased procedural and technical complexity. For example, repetitive transcranial magnetic stimulation (rTMS) and 4 × 1/2 × 2 high-definition transcranial direct current stimulation (4 × 1/2 × 2 HD-tDCS) are largely center-based, with unilateral-target focus-bilateral excitation would require two rTMS/4 × 1 HD-tDCS systems. We developed a system that allows for focal, non-invasive, self-applied, and simultaneous bilateral excitatory M1 stimulation, supporting long-term home-based treatment with a well-tolerated wearable battery-powered device. Here, we overviewed the most employed M1 neuromodulation methods, from invasive techniques to non-invasive TMS and tDCS. The evaluation extended from non-invasive diffuse asymmetric bilateral (M1-supraorbital [SO] tDCS), non-invasive and invasive unilateral focal (4 × 1/2 × 2 HD-tDCS, rTMS, MCS), to non-invasive and invasive bilateral bipolar (M1-M1 tDCS, MCS), before outlining our proposal for a neuromodulatory system with unique features. Computational models were applied to compare brain current flow for current laboratory-based unilateral M1 and bilateral M1 HD-tDCS models with a functional home-based M1 HD-tDCS prototype. We concluded the study by discussing the promising concept of bilateral excitatory M1 stimulation for more global pain relief, which is also non-invasive, focal, and home-based.
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http://dx.doi.org/10.3389/fpain.2022.798056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8915734PMC
February 2022

Short-Term Efficacy of Transcranial Focused Ultrasound to the Hippocampus in Alzheimer's Disease: A Preliminary Study.

J Pers Med 2022 Feb 9;12(2). Epub 2022 Feb 9.

Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

Preclinical studies have suggested that low-intensity transcranial focused ultrasound (tFUS) may have therapeutic potential for Alzheimer's disease (AD) by opening the blood-brain barrier (BBB), reducing amyloid pathology, and improving cognition. This study investigated the effects of tFUS on BBB opening, regional cerebral metabolic rate of glucose (rCMRglu), and cognitive function in AD patients. Eight patients with AD received image-guided tFUS to the right hippocampus immediately after intravenous injection of microbubble ultrasound contrast agents. Patients completed magnetic resonance imaging (MRI), F-fluoro-2-deoxyglucose positron emission tomography (PET), and cognitive assessments before and after the sonication. No evidence of transient BBB opening was found on T1 dynamic contrast-enhanced MRI. However, immediate recall ( = 0.03) and recognition memory ( = 0.02) were significantly improved on the verbal learning test. PET image analysis demonstrated increased rCMRglu in the right hippocampus ( = 0.001). In addition, increases of hippocampal rCMRglu were correlated with improvement in recognition memory (Spearman's = 0.77, = 0.02). No adverse event was observed. Our results suggest that tFUS to the hippocampus of AD patients may improve rCMRglu of the target area and memory in the short term, even without BBB opening. Further larger sham-controlled trials with loger follow-up are warranted to evaluate the efficacy and safety of tFUS in patients with AD.
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http://dx.doi.org/10.3390/jpm12020250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8878180PMC
February 2022

Factors supporting availability of home-based Neuromodulation using remote supervision in middle-income countries; Brazil experience.

Brain Stimul 2022 Mar-Apr;15(2):385-387. Epub 2022 Feb 15.

Department of Biomedical Engineering, The City College of New York of CUNY, New York, NY, USA.

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http://dx.doi.org/10.1016/j.brs.2022.02.005DOI Listing
April 2022

A checklist for assessing the methodological quality of concurrent tES-fMRI studies (ContES checklist): a consensus study and statement.

Nat Protoc 2022 03 4;17(3):596-617. Epub 2022 Feb 4.

Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, Italy.

Low-intensity transcranial electrical stimulation (tES), including alternating or direct current stimulation, applies weak electrical stimulation to modulate the activity of brain circuits. Integration of tES with concurrent functional MRI (fMRI) allows for the mapping of neural activity during neuromodulation, supporting causal studies of both brain function and tES effects. Methodological aspects of tES-fMRI studies underpin the results, and reporting them in appropriate detail is required for reproducibility and interpretability. Despite the growing number of published reports, there are no consensus-based checklists for disclosing methodological details of concurrent tES-fMRI studies. The objective of this work was to develop a consensus-based checklist of reporting standards for concurrent tES-fMRI studies to support methodological rigor, transparency and reproducibility (ContES checklist). A two-phase Delphi consensus process was conducted by a steering committee (SC) of 13 members and 49 expert panelists through the International Network of the tES-fMRI Consortium. The process began with a circulation of a preliminary checklist of essential items and additional recommendations, developed by the SC on the basis of a systematic review of 57 concurrent tES-fMRI studies. Contributors were then invited to suggest revisions or additions to the initial checklist. After the revision phase, contributors rated the importance of the 17 essential items and 42 additional recommendations in the final checklist. The state of methodological transparency within the 57 reviewed concurrent tES-fMRI studies was then assessed by using the checklist. Experts refined the checklist through the revision and rating phases, leading to a checklist with three categories of essential items and additional recommendations: (i) technological factors, (ii) safety and noise tests and (iii) methodological factors. The level of reporting of checklist items varied among the 57 concurrent tES-fMRI papers, ranging from 24% to 76%. On average, 53% of checklist items were reported in a given article. In conclusion, use of the ContES checklist is expected to enhance the methodological reporting quality of future concurrent tES-fMRI studies and increase methodological transparency and reproducibility.
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http://dx.doi.org/10.1038/s41596-021-00664-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7612687PMC
March 2022

Transcranial Direct Current Stimulation on Parkinson's Disease: Systematic Review and Meta-Analysis.

Front Neurol 2021 10;12:794784. Epub 2022 Jan 10.

Program in Neuroengineering, Edmond and Lily Safra International Institute of Neuroscience, Santos Dumont Institute, Macaíba, Brazil.

Clinical impact of transcranial direct current stimulation (tDCS) alone for Parkinson's disease (PD) is still a challenge. Thus, there is a need to synthesize available results, analyze methodologically and statistically, and provide evidence to guide tDCS in PD. Investigate isolated tDCS effect in different brain areas and number of stimulated targets on PD motor symptoms. A systematic review was carried out up to February 2021, in databases: Cochrane Library, EMBASE, PubMed/MEDLINE, Scopus, and Web of science. Full text articles evaluating effect of active tDCS (anodic or cathodic) vs. sham or control on motor symptoms of PD were included. Ten studies ( = 236) were included in meta-analysis and 25 studies ( = 405) in qualitative synthesis. The most frequently stimulated targets were dorsolateral prefrontal cortex and primary motor cortex. No significant effect was found among single targets on motor outcomes: Unified Parkinson's Disease Rating Scale (UPDRS) III - motor aspects (MD = -0.98%, 95% CI = -10.03 to 8.07, = 0.83, = 0%), UPDRS IV - dyskinesias (MD = -0.89%, CI 95% = -3.82 to 2.03, = 0.55, = 0%) and motor fluctuations (MD = -0.67%, CI 95% = -2.45 to 1.11, = 0.46, = 0%), timed up and go - gait (MD = 0.14%, CI 95% = -0.72 to 0.99, = 0.75, = 0%), Berg Balance Scale - balance (MD = 0.73%, CI 95% = -1.01 to 2.47, = 0.41, = 0%). There was no significant effect of single vs. multiple targets in: UPDRS III - motor aspects (MD = 2.05%, CI 95% = -1.96 to 6.06, = 0.32, = 0%) and gait (SMD = -0.05%, 95% CI = -0.28 to 0.17, = 0.64, = 0%). Simple univariate meta-regression analysis between treatment dosage and effect size revealed that number of sessions (estimate = -1.7, SE = 1.51, z-score = -1.18, = 0.2, IC = -4.75 to 1.17) and cumulative time (estimate = -0.07, SE = 0.07, z-score = -0.99, = 0.31, IC = -0.21 to 0.07) had no significant association. There was no significant tDCS alone short-term effect on motor function, balance, gait, dyskinesias or motor fluctuations in Parkinson's disease, regardless of brain area or targets stimulated.
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http://dx.doi.org/10.3389/fneur.2021.794784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8785799PMC
January 2022

A visual and narrative timeline of US FDA milestones for Transcranial Magnetic Stimulation (TMS) devices.

Brain Stimul 2022 Jan-Feb;15(1):73-75. Epub 2021 Nov 11.

Department of Psychiatry, Medical University of South Carolina, Charleston, SC, 29425, USA; Ralph H. Johnson VA Medical Center, Charleston, SC, 29401, USA.

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http://dx.doi.org/10.1016/j.brs.2021.11.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8864803PMC
March 2022

Weak DCS causes a relatively strong cumulative boost of synaptic plasticity with spaced learning.

Brain Stimul 2022 Jan-Feb;15(1):57-62. Epub 2021 Nov 5.

Department of Biomedical Engineering, The City College of New York, CUNY, 160 Convent Avenue, New York, NY, USA. Electronic address:

Background: Electric fields generated during direct current stimulation (DCS) are known to modulate activity-dependent synaptic plasticity in-vitro. This provides a mechanistic explanation for the lasting behavioral effects observed with transcranial direct current stimulation (tDCS) in human learning experiments. However, previous in-vitro synaptic plasticity experiments show relatively small effects despite using strong fields compared to what is expected with conventional tDCS in humans (20 V/m vs. 1 V/m). There is therefore a need to improve the effectiveness of tDCS at realistic field intensities. Here we leverage the observation that effects of learning are known to accumulate over multiple bouts of learning, known as spaced learning.

Hypothesis: We propose that effects of DCS on synaptic long-term potentiation (LTP) accumulate over time in a spaced learning paradigm, thus revealing effects at more realistic field intensities.

Methods: We leverage a standard model for spaced learning by inducing LTP with repeated bouts of theta burst stimulation (TBS) in hippocampal slice preparations. We studied the cumulative effects of DCS paired with TBS at various intensities applied during the induction of LTP in the CA1 region of rat hippocampal slices.

Results: As predicted, DCS applied during repeated bouts of theta burst stimulation (TBS) resulted in an increase of LTP. This spaced learning effect is saturated quickly with strong TBS protocols and stronger fields. In contrast, weaker TBS and the weakest electric fields of 2.5 V/m resulted in the strongest relative efficacies (12% boost in LTP per 1 V/m applied).

Conclusions: Weak DCS causes a relatively strong cumulative effect of spaced learning on synaptic plasticity. Staturarion may have masked stronger effects sizes in previous in-vitro studies. Relative effect sizes of DCS are now closer in line with human tDCS experiments.
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http://dx.doi.org/10.1016/j.brs.2021.10.552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8816825PMC
March 2022

Dataset of concurrent EEG, ECG, and behavior with multiple doses of transcranial electrical stimulation.

Sci Data 2021 10 27;8(1):274. Epub 2021 Oct 27.

The Department of Biomedical Engineering, The City College of New York, The City University of New York, New York, USA.

We present a dataset combining human-participant high-density electroencephalography (EEG) with physiological and continuous behavioral metrics during transcranial electrical stimulation (tES). Data include within participant application of nine High-Definition tES (HD-tES) types, targeting three cortical regions (frontal, motor, parietal) with three stimulation waveforms (DC, 5 Hz, 30 Hz); more than 783 total stimulation trials over 62 sessions with EEG, physiological (ECG, EOG), and continuous behavioral vigilance/alertness metrics. Experiment 1 and 2 consisted of participants performing a continuous vigilance/alertness task over three 70-minute and two 70.5-minute sessions, respectively. Demographic data were collected, as well as self-reported wellness questionnaires before and after each session. Participants received all 9 stimulation types in Experiment 1, with each session including three stimulation types, with 4 trials per type. Participants received two stimulation types in Experiment 2, with 20 trials of a given stimulation type per session. Within-participant reliability was tested by repeating select sessions. This unique dataset supports a range of hypothesis testing including interactions of tDCS/tACS location and frequency, brain-state, physiology, fatigue, and cognitive performance.
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http://dx.doi.org/10.1038/s41597-021-01046-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8551279PMC
October 2021

Direct Current Stimulation Disrupts Endothelial Glycocalyx and Tight Junctions of the Blood-Brain Barrier .

Front Cell Dev Biol 2021 28;9:731028. Epub 2021 Sep 28.

Department of Biomedical Engineering, The City College of the City University of New York, New York, NY, United States.

Transcranial direct current stimulation (tDCS) is a non-invasive physical therapy to treat many psychiatric disorders and to enhance memory and cognition in healthy individuals. Our recent studies showed that tDCS with the proper dosage and duration can transiently enhance the permeability (P) of the blood-brain barrier (BBB) in rat brain to various sized solutes. Based on the permeability data, a transport model for the paracellular pathway of the BBB also predicted that tDCS can transiently disrupt the endothelial glycocalyx (EG) and the tight junction between endothelial cells. To confirm these predictions and to investigate the structural mechanisms by which tDCS modulates P of the BBB, we directly quantified the EG and tight junctions of BBB models after DCS treatment. Human cerebral microvascular endothelial cells (hCMECs) and mouse brain microvascular endothelial cells (bEnd3) were cultured on the Transwell filter with 3 μm pores to generate BBBs. After confluence, 0.1-1 mA/cm DCS was applied for 5 and 10 min. TEER and P to dextran-70k of the BBB were measured, HS (heparan sulfate) and hyaluronic acid (HA) of EG was immuno-stained and quantified, as well as the tight junction ZO-1. We found disrupted EG and ZO-1 when P to dextran-70k was increased and TEER was decreased by the DCS. To further investigate the cellular signaling mechanism of DCS on the BBB permeability, we pretreated the BBB with a nitric oxide synthase (NOS) inhibitor, L-NMMA. L-NMMA diminished the effect of DCS on the BBB permeability by protecting the EG and reinforcing tight junctions. These results conform to the observations and confirm the model prediction that DCS can disrupt the EG and tight junction of the BBB. Nevertheless, the effects of DCS are transient which backup its safety in the clinical application. In conclusion, our current study directly elucidates the structural and signaling mechanisms by which DCS modulates the BBB permeability.
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http://dx.doi.org/10.3389/fcell.2021.731028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8505730PMC
September 2021

High-resolution computational modeling of the current flow in the outer ear during transcutaneous auricular Vagus Nerve Stimulation (taVNS).

Brain Stimul 2021 Nov-Dec;14(6):1419-1430. Epub 2021 Sep 10.

Department of Biomedical Engineering, The City College of New York, New York, NY, USA. Electronic address:

Background: Transcutaneous auricular Vagus Nerve Stimulation (taVNS) applies low-intensity electrical current to the ear with the intention of activating the auricular branch of the Vagus nerve. The sensitivity and selectivity of stimulation applied to the ear depends on current flow pattern produced by a given electrode montage (size and placement).

Objective: We compare different electrodes designs for taVNS considering both the predicted peak electric fields (sensitivity) and their spatial distribution (selectivity).

Methods: Based on optimized high-resolution (0.47 mm) T1 and T2 weighted MRI, we developed an anatomical model of the left ear and the surrounding head tissues including brain, CSF/meninges, skull, muscle, blood vessels, fat, cartilage, and skin. The ear was further segmented into 6 regions of interest (ROI) based on various nerve densities: cavum concha, cymba concha, crus of helix, tragus, antitragus, and earlobe. A range of taVNS electrode montages were reproduced spanning varied electrodes sizes and placements over the tragus, cymba concha, earlobe, cavum concha, and crus of helix. Electric field across the ear (from superficial skin to cartilage) for each montage at 1 mA or 2 mA taVNS, assuming an activation threshold of 6.15 V/m, 12.3 V/m or 24.6 V/m was predicted using a Finite element method (FEM). Finally, considering every ROI, we calculated the sensitivity and selectivity of each montage.

Results: Current flow patterns through the ear were highly specific to the electrode montage. Electric field was maximal at the ear regions directly under the electrodes, and for a given total current, increases with decreasing electrode size. Depending on the applied current and nerves threshold, activation may also occur in the regions between multiple anterior surface electrodes. Each considered montage was selective for one or two regions of interest. For example, electrodes across the tragus restricted significant electric field to the tragus. Stimulation across the earlobe restricted significant electric field to the earlobe and the antitragus. Because of this relative selectivity, use of control ear montages in experimental studies, support testing of targeting. Relative targeting was robust across assumptions of activation threshold and tissue properties.

Discussion: Computational models provide additional insight on how details in electrode shape and placement impact sensitivity (how much current is needed) and selectivity (spatial distribution), thereby supporting analysis of existing approaches and optimization of new devices. Our result suggest taVNS current patterns and relative target are robust across individuals, though (variance in) axon morphology was not represented.
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http://dx.doi.org/10.1016/j.brs.2021.09.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8608747PMC
March 2022

Effects of transcranial direct current stimulation associated with an aerobic exercise bout on blood pressure and autonomic modulation of hypertensive patients: A pilot randomized clinical trial.

Auton Neurosci 2021 11 6;235:102866. Epub 2021 Aug 6.

Associated graduate Program in Physical Education, Federal University of Paraíba, João Pessoa, Paraíba, Brazil.

The objective of this article was to evaluate the effects of an aerobic exercise bout associated with a single session of anodal transcranial direct current stimulation (tDCS) over the left temporal lobe on blood pressure (BP) and heart rate variability (HRV) in hypertensive people. After met the inclusion criteria, twenty hypertensive people were randomized to active-tDCS or sham-tDCS group. Initially, they provided their sociodemographic data, a blood sample, and went through an evaluation of the cardiorespiratory performance. Then, a single session of tDCS with an intensity of 2 mA over the left lobe during 20 min was carried out. After tDCS, it was performed a session of moderate-intensity aerobic exercise during 40 min. BP during 24 h and HRV measurements were performed before (baseline) and after the intervention. Systolic BP during sleep time decreased in the active-tDCS group (p = 0.008). Diastolic BP showed a significant decrease 3 h after the intervention in the active-tDCS group (p = 0.01). An intragroup comparison showed a significant decrease in systolic BP 3 h after intervention only for the active-tDCS group (p = 0.04). Besides, there was a trend toward a difference in wake for diastolic BP for active-tDCS (p = 0.07). Lastly, there were no changes in the HRV for both groups. It is suggested that anodal tDCS associated with moderate-intensity aerobic exercise can decrease systolic and diastolic BP of hypertensive people during sleep time and 3 h after the intervention.
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http://dx.doi.org/10.1016/j.autneu.2021.102866DOI Listing
November 2021

Adaptive current-flow models of ECT: Explaining individual static impedance, dynamic impedance, and brain current density.

Brain Stimul 2021 Sep-Oct;14(5):1154-1168. Epub 2021 Jul 28.

Department of Biomedical Engineering, The City College of New York, CUNY, New York, NY, USA. Electronic address:

Background: Improvements in electroconvulsive therapy (ECT) outcomes have followed refinement in device electrical output and electrode montage. The physical properties of the ECT stimulus, together with those of the patient's head, determine the impedances measured by the device and govern current delivery to the brain and ECT outcomes.

Objective: However, the precise relations among physical properties of the stimulus, patient head anatomy, and patient-specific impedance to the passage of current are long-standing questions in ECT research and practice. To this end, we develop a computational framework based on diverse clinical data sets.

Methods: We developed anatomical MRI-derived models of transcranial electrical stimulation (tES) that included changes in tissue conductivity due to local electrical current flow. These "adaptive" models simulate ECT both during therapeutic stimulation using high current (∼1 A) and when dynamic impedance is measured, as well as prior to stimulation when low current (∼1 mA) is used to measure static impedance. We modeled two scalp layers: a superficial scalp layer with adaptive conductivity that increases with electric field up to a subject-specific maximum (σ), and a deep scalp layer with a subject-specific fixed conductivity (σ).

Results: We demonstrated that variation in these scalp parameters may explain clinical data on subject-specific static impedance and dynamic impedance, their imperfect correlation across subjects, their relationships to seizure threshold, and the role of head anatomy. Adaptive tES models demonstrated that current flow changes local tissue conductivity which in turn shapes current delivery to the brain in a manner not accounted for in fixed tissue conductivity models.

Conclusions: Our predictions that variation in individual skin properties, rather than other aspects of anatomy, largely govern the relationship between static impedance, dynamic impedance, and ECT current delivery to the brain, themselves depend on assumptions about tissue properties. Broadly, our novel modeling pipeline opens the door to explore how adaptive-scalp conductivity may impact transcutaneous electrical stimulation (tES).
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http://dx.doi.org/10.1016/j.brs.2021.07.012DOI Listing
November 2021

Acute effect of high-definition and conventional tDCS on exercise performance and psychophysiological responses in endurance athletes: a randomized controlled trial.

Sci Rep 2021 07 6;11(1):13911. Epub 2021 Jul 6.

Associate Graduate Program in Physical Education - UEM/UEL, State University of Londrina, Londrina, PR, Brazil.

Transcranial direct current stimulation (tDCS) has been used aiming to boost exercise performance and inconsistent findings have been reported. One possible explanation is related to the limitations of the so-called "conventional" tDCS, which uses large rectangular electrodes, resulting in a diffuse electric field. A new tDCS technique called high-definition tDCS (HD-tDCS) has been recently developed. HD-tDCS uses small ring electrodes and produces improved focality and greater magnitude of its aftereffects. This study tested whether HD-tDCS would improve exercise performance to a greater extent than conventional tDCS. Twelve endurance athletes (29.4 ± 7.3 years; 60.15 ± 5.09 ml kg min) were enrolled in this single-center, randomized, crossover, and sham-controlled trial. To test reliability, participants performed two time to exhaustion (TTE) tests (control conditions) on a cycle simulator with 80% of peak power until volitional exhaustion. Next, they randomly received HD-tDCS (2.4 mA), conventional (2.0 mA), or active sham tDCS (2.0 mA) over the motor cortex for 20-min before performing the TTE test. TTE, heart rate (HR), associative thoughts, peripheral (lower limbs), and whole-body ratings of perceived exertion (RPE) were recorded every minute. Outcome measures were reliable. There was no difference in TTE between HD-tDCS (853.1 ± 288.6 s), simulated conventional (827.8 ± 278.7 s), sham (794.3 ± 271.2 s), or control conditions (TTE1 = 751.1 ± 261.6 s or TTE2 = 770.8 ± 250.6 s) [F = 1.537; P = 0.24; ηp = 0.123]. There was no effect on peripheral or whole-body RPE and associative thoughts (P > 0.05). No serious adverse effect was reported. A single session of neither HD-tDCS nor conventional tDCS changed exercise performance and psychophysiological responses in athletes, suggesting that a ceiling effect may exist.
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http://dx.doi.org/10.1038/s41598-021-92670-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260713PMC
July 2021

PRIMED Preclinical Evidence Scoring Tool to Assess Readiness for Translation of Neuroprotection Therapies.

Transl Stroke Res 2022 04 1;13(2):222-227. Epub 2021 Jul 1.

Department of Neurology and Comprehensive Stroke Center, David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA, 90095, USA.

Many neuroprotective and other therapies for treatment of acute ischemic stroke have failed in translation to human studies, indicating a need for more rigorous, multidimensional quality assessment of the totality of preclinical evidence supporting a therapy prior to conducting human trials. A consensus panel of stroke preclinical model and human clinical trial experts assessed candidate items for the translational readiness scale, compiled from prior instruments (STAIR, ARRIVE, CAMARADES, RoB 2) based on importance, reliability, and feasibility. Once constructed, the tool was applied by two independent raters to four current candidate acute stroke therapies, including two pharmacologic agents [nerinetide and trans-sodium crocetinate] and two device interventions [cathodal transcranial direct current stimulation and fastigial nucleus stimulation]. The Preclinical evidence of Readiness In stroke Models Evaluating Drugs and Devices (PRIMED) assessment tool rates the totality of evidence available from all reported preclinical animal stroke model studies in 11 domains related to diversity of tested animals, time windows, feasibility of agent route of delivery, and robustness of effect magnitude. Within each content domain, clearly operationalized rules assign strength of evidence ratings of 0-2. When applied to the four assessed candidate agents, inter-rater reliability was high (kappa = 0.88), and each agent showed a unique profile of evidentiary strengths and weaknesses. The PRIMED assessment tool provides a multidimensional assessment of the cumulative preclinical evidence for a candidate acute stroke therapy on factors judged important for successful basic-to-clinical translation. Further evaluation and refinement of this tool is desirable to improve successful translation of therapies for acute stroke.
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http://dx.doi.org/10.1007/s12975-021-00922-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8918446PMC
April 2022
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