New Paper: The Quasi-uniform assumption for Spinal Cord Stimulation translational research

Niranjan Khadka, Dennis Q. Truong, Preston Williams, John H. Martin, Marom Bikson. The Quasi-uniform assumption for Spinal Cord Stimulation translational research. Journal of Neuroscience Methods. https://doi.org/10.1016/j.jneumeth.2019.108446


Download PDF published in Journal Neuroscience Methods— DOI

Abstract

Background: Quasi-uniform assumption is a general theory that postulates local electric field predicts neuronal activation. Computational current flow model of spinal cord stimulation (SCS) of humans and animal models inform how the quasi-uniform assumption can support scaling neuromodulation dose between humans and translational animal.

New method: Here we developed finite element models of cat and rat SCS, and brain slice, alongside SCS models. Boundary conditions related to species specific electrode dimensions applied, and electric fields per unit current (mA) predicted.

Results: Clinically and across animal, electric fields change abruptly over small distance compared to the neuronal morphology, such that each neuron is exposed to multiple electric fields. Per unit current, electric fields generally decrease with body mass, but not necessarily and proportionally across tissues. Peak electric field in dorsal column rat and cat were ∼17x and ∼1x of clinical values, for scaled electrodes and equal current. Within the spinal cord, the electric field for rat, cat, and human decreased to 50% of peak value caudo-rostrally (C5–C6) at 0.48 mm, 3.2 mm, and 8 mm, and mediolaterally at 0.14 mm, 2.3 mm, and 3.1 mm. Because these space constants are different, electric field across species cannot be matched without selecting a region of interest (ROI)

Comparison of existing method: This is the first computational model to support scaling neuromodulation dose between humans and translational animal.

Conclusions: Inter-species reproduction of the electric field profile across the entire surface of neuron populations is intractable. Approximating quasi-uniform electric field in a ROI is a rational step to translational scaling.

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Niranjan K
CCNY Neural Engineering lab presents innovative projects at the 2019 Joint Meeting of Neuromodulation: The Science & NYC Neuromodulation
  1. Bio-heat model of kilohertz-frequency Deep Brain Stimulation increases brain tissue temperature

    Niranjan Khadka, Irene Harmsen, Andres M. Lozano, Marom Bikson

  2. Tissue Temperature Increases by a 10 kHz Frequency Spinal Cord Stimulation System: Phantom and Bioheat Model

    Adantachede L Zannou, Niranjan Khadka, Mohmad FallahRad, Dennis Q. Truong, Brian H Kopell, Marom Bikson

  3. Modulation of Sleepiness and Physiology with Brain-Derived and Narrow-Band tACS

    Nigel Gebodh, Laura Vacchi, Zeinab Esmaeilpour, Devin Adair, Alexander Poltorak, Valeria Poltorak, Marom Bikson

  4. Realistic Anatomically Detailed Open-source Spinal Cord Stimulation (RADO SCS) Model

    Niranjan Khadka, Xijie Liu, Jaiti Swami, Hans Zander, Evan Rogers, Scott Lempka, Marom Bikson

    Download: PDF

  5. Mechanism of Temporal Interference (TI) stimulation

    Zeinab Esmaeilpour, Greg Kronberg, Lucas Parra, Marom Bikson

Niranjan K
New Paper: Adaptive current tDCS up to 4 mA

Niranjan Khadka, Helen Borges, Bhaskar Paneri, Trynia Kaufman, Electra Nassis, Adantchede L. Zannou, Yungjae Shin, Hyeongseob Choi, Seonghoon Kim, Kiwon Lee, Marom Bikson. Adaptive current tDCS up to 4 mA. Brain Stimulation. https://doi.org/10.1016/j.brs.2019.07.027. PDF


Download: PDF published in Brain Stimulation — DOI

Abstract

Background: Higher tDCS current may putatively enhance efficacy, with tolerability the perceived limiting factor.

Objective: We designed and validated electrodes and an adaptive controller to provide tDCS up to 4 mA,while managing tolerability. The adaptive 4 mA controller included incremental ramp up, impedance-based current limits, and a Relax-mode where current is transiently decreased. Relax-mode was automatically activated by self-report VAS-pain score>5 and in some conditions by a Relax-button available to participants.

Methods: In a parallel-group participant-blind design with 50 healthy subjects, we used specialized electrodes to administer 3 daily session of tDCS for 11 min, with a lexical decision task as a distractor, in 5 study conditions: adaptive 4 mA, adaptive 4 mA with Relax-button, adaptive 4 mA with historical-Relax-button, 2 mA, and sham. A tablet-based stimulator with a participant interface regularly queried VAS pain score and also limited current based on impedance and tolerability. An Abort-button provided in all conditions stopped stimulation. In the adaptive 4 mA with Relax-button and adaptive 4 mA with historical-Relax-button conditions, participants could trigger a Relax-mode ad libitum, in the latter case with incrementally longer current reductions. Primary outcome was the average current delivered during each session, VAS pain score, and adverse event questionnaires. Current delivered was analyzed either excluding or including dropouts who activated Abort (scored as 0 current).

Results: There were two dropouts each in the adaptive 4 mA and sham conditions. Resistance based current attenuation was rarely activated, with few automatic VAS pain score triggered relax-modes. In conditions with Relax-button option, there were significant activation often irrespective of VAS pain score. Including dropouts, current across conditions were significantly different from each other with maximum current delivered during adaptive 4 mA with Relax-button. Excluding dropouts, maximum current was delivered with adaptive 4 mA. VAS pain score and adverse events for the sham was only significantly lower than the adaptive 4 mA with Relax-button and adaptive 4 mA with historical-Relax-button. There was no difference in VAS pain score or adverse events between 2 mA and adaptive 4 mA.

Conclusions: Provided specific electrodes and controllers, adaptive 4 mA tDCS is tolerated and effectively blinded, with acceptability likely higher in a clinical population and absence of regular querying. Indeed,presenting participants with overt controls increases rumination on sensation.

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Bikson features in IEEE "How a Tiny Electrical Current to the Brain is Treating Medical Symptoms"
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Prof. Marom Bikson discusses both home-based tDCS and HD-tDCS in IEEE “How a Tiny Electrical Current to the Brain Is Treating Medical Symptoms”.

Read the article: PDF

“Bikson, professor of biomedical engineering at City University of New York (CUNY). He is also cofounder of Soterix Medical of New York City, which is developing tDCS for home, clinical, and research applications. On the medical-supervision side, Soterix is working on an automated home system that a clinician (or researcher if it’s part of a research project) can monitor and direct via telemedicine (Figure 4). “There’s a lot of technology that goes into that, including reliable communication between the technology and the site that’s providing the telemedicine, as well as automated software that can collect information from the patient on a daily basis, and can also deliver the prescription that the doctor sets,” Bikson said. “Although the software doesn’t decide what the treatment will be, it can withhold treatment until the patient is ready to receive it based on the doctor’s prescription schedule.”

“Going high-def: Besides the home-based tDCS system, Soterix also developed something quite different for use in research labs and clinics: targeted tDCS that delivers current to precise, small areas of the brain, as compared to the 5x5-cm areas covered by each of the two pads or sponges seen in typical home based systems, Bikson explained. The idea with targeted tDCS is to personalize treatment for individual patients and/or to reduce distinct symptoms. Soterix actually engineered the first noninvasive, targeted, and low-intensity neuromodulation technology, dubbed high-definition tDCS (HD-tDCS), back in 2009. “HD-tDCS and its variants, which include HD-tACS, use an array of smaller electrodes to stimulate specific parts of the brain,”

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Marom Bikson
New Paper: Transcranial electrical stimulation nomenclature

Bikson M, Esmaeilpour Z, Adair D, Kronberg G, Tyler WJ, Antal A, Datta A, Sabel BA, Nitsche MA, Loo C, Edwards D, Ekhtiari H, Knotkova H, Woods AJ, Hampstead BM, Badran BW, Peterchev AV. (2019). Transcranial electrical stimulation nomenclature. Brain Stimulation. https://doi.org/10.1016/j.brs.2019.07.010 PDF

Download: PDF published in Brain Stimulation – DOI


Abstract

Transcranial electrical stimulation (tES) aims to alter brain function non-invasively by applying current to electrodes on the scalp. Decades of research and technological advancement are associated with a growing diversity of tES methods and the associated nomenclature for describing these methods. Whether intended to produce a specific response so the brain can be studied or lead to a more enduring change in behavior (e.g. for treatment), the motivations for using tES have themselves influenced the evolution of nomenclature, leading to some scientific, clinical, and public confusion. This ambiguity arises from (i) the infinite parameter space available in designing tES methods of application and (ii) varied naming conventions based upon the intended effects and/or methods of application. Here, we compile a cohesive nomenclature for contemporary tES technologies that respects existing and historical norms, while incorporating insight and classifications based on state-of-the-art findings. We consolidate and clarify existing terminology conventions, but do not aim to create new nomenclature. The presented nomenclature aims to balance adopting broad definitions that encourage flexibility and innovation in research approaches, against classification specificity that minimizes ambiguity about protocols but can hinder progress. Constructive research around tES classification, such as transcranial direct current stimulation (tDCS), should allow some variations in protocol but also distinguish from approaches that bear so little resemblance that their safety and efficacy should not be compared directly. The proposed framework includes terms in contemporary use across peer-reviewed publications, including relatively new nomenclature introduced in the past decade, such as transcranial alternating current stimulation (tACS) and transcranial pulsed current stimulation (tPCS), as well as terms with long historical use such as electroconvulsive therapy (ECT). We also define commonly used terms-of-the-trade including electrode, lead, anode, and cathode, whose prior use, in varied contexts, can also be a source of confusion. This comprehensive clarification of nomenclature and associated preliminary proposals for standardized terminology can support the development of consensus on efficacy, safety, and regulatory standards.

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Preprint: Computational FEM forward modeling workflow for tDCS on MRI-derived head: Simpleware/COMSOL tutorial.

Computational Finite Element Method (FEM) forward modeling workflow for transcranial Direct Current Stimulation (tDCS) current flow on MRI-derived head: Simpleware and COMSOL Multiphysics tutorial. Ole Seibt, Dennis Truong, Niranjan Khadka, Yu Huang, Marom Bikson. bioRxiv 704940; doi: https://doi.org/10.1101/704940


Download PDF from bioRxiv - DOI

Abstract

Transcranial Direct Current Stimulation (tDCS) dose designs are often based on computational Finite Element Method (FEM) forward modeling studies. These FEM models educate researchers about the resulting current flow (intensity and pattern) and so the resulting neurophysiological and behavioral changes based on tDCS dose (mA), resistivity of head tissues (e.g. skin, skull, CSF, brain), and head anatomy. Moreover, model support optimization of montage to target specific brain regions. Computational models are thus an ancillary tool used to inform the design, set-up and programming of tDCS devices, and investigate the role of parameters such as electrode assembly, current directionality, and polarity of tDCS in optimizing therapeutic interventions. Computational FEM modeling pipeline of tDCS initiates with segmentation of an exemplary magnetic resonance imaging (MRI) scan of a template head into multiple tissue compartments to develop a higher resolution (< 1 mm) MRI derived FEM model using Simpleware ScanIP. Next, electrode assembly (anode and cathode of variant dimension) is positioned over the brain target and meshed at different mesh densities. Finally, a volumetric mesh of the head with electrodes is imported in COMSOL and a quasistatic approximation (stead-state solution method) is implemented with boundary conditions such as inward normal current density (anode), ground (cathode), and electrically insulating remaining boundaries. A successfully solved FEM model is used to visualize the model prediction via different plots (streamlines, volume plot, arrow plot).

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New Paper: Language boosting by transcranial stimulation in progressive supranuclear palsy

Valero-Cabré A, Sanches C, Godard J, Fracchia O, Dubois B, Levy R, Truong DQ, Bikson M, Teichmann M. (2019). Language boosting by transcranial stimulation in progressive supranuclear palsy. Neurology, 10.1212/WNL.0000000000007893. https://doi.org/10.1212/wnl.0000000000007893. PDF


Download: PDF published in Neurology – DOI

Abstract

[Our objective was t]o explore whether transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) can improve language capacities in patients with progressive supranuclear palsy (PSP). We used a sham-controlled double-blind crossover design to assess the efficiency of tDCS over the DLPFC in a cohort of 12 patients with PSP. In 3 separate sessions, we evaluated the ability to boost the left DLPFC via left-anodal (excitatory) and right-cathodal (inhibitory) tDCS, while comparing them to sham tDCS. Tasks assessing lexical access (letter fluency task) and semantic access (category judgment task) were applied immediately before and after the tDCS sessions to provide a marker of potential language modulation. The comparison with healthy controls showed that patients with PSP were impaired on both tasks at baseline. Contrasting poststimulation vs prestimulation performance across tDCS conditions revealed language improvement in the category judgment task following right-cathodal tDCS, and in the letter fluency task following left-anodal tDCS. A computational finite element model of current distribution corroborated the intended effect of left-anodal and right-cathodal tDCS on the targeted DLPFC. Our results demonstrate tDCS-driven language improvement in PSP. They provide proof-of-concept for the use of tDCS in PSP and set the stage for future multiday stimulation regimens, which might lead to longer-lasting therapeutic effects promoted by neuroplasticity. This study provides Class III evidence that for patients with PSP, tDCS over the DLPFC improves performance in some language tasks.

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Bikson gives Hands-On Workshop and Plenary lecture at BIOEM 2019

June 23-24, 2019 at the BioEM2019  The Bioelectromagnetics Society (BEMS) and the European BioElectromagnetics Association (EBEA) joint meeting in Montpellier, France

Prof. Marom Bikson instructs on “Theory and hands-on practical for tDCS and tACS” June 23, 2019 Details   slides :tdcs_tacs_2019_final-compressed

and gives plenary lecture on “Electrical Brain Stimulation” on June 24, 2019. Conference website  slides: BioEM_2019_Final_Bikson-compressed

Pictures from the event

Neural Engineering
New Paper: Tissue Temperature Increases by a 10 kHz Spinal Cord Stimulation System: Phantom and Bioheat Model

Zannou AL, Khadka N, Truong D, FallahRad M, Kopell B, Bikson, M. Tissue Temperature Increases by a 10 kHz Spinal Cord Stimulation System: Phantom and Bioheat Model. Neuromodulation: Technology at the Neural Interface. https://doi.org/10.1111/ner.12980. 2019. PDF

Download: PDF published in Neuromodulation: Technology at the Neural Interface – DOI

Abstract

A recently introduced Spinal Cord Stimulation (SCS) system operates at 10 kHz, faster than conventional SCS systems, resulting in significantly more power delivered to tissues. Using a SCS heat phantom and bioheat multi‐physics model, we characterized tissue temperature increases by this 10 kHz system. We also evaluated its Implanted Pulse Generator (IPG) output compliance and the role of impedance in temperature increases. The 10 kHz SCS system output was characterized under resistive loads (1–10 KΩ). Separately, fiber optic temperature probes quantified temperature increases (ΔTs) around the SCS lead in specially developed heat phantoms. The role of stimulation Level (1–7; ideal pulse peak‐to‐peak of 1–7mA) was considered, specifically in the context of stimulation current Root Mean Square (RMS). Data from the heat phantom were verified with the SCS heat‐transfer models. A custom high‐bandwidth stimulator provided 10 kHz pulses and sinusoidal stimulation for control experiments. The 10 kHz SCS system delivers 10 kHz biphasic pulses (30‐20‐30 μs). Voltage compliance was 15.6V. Even below voltage compliance, IPG bandwidth attenuated pulse waveform, limiting applied RMS. Temperature increased supralinearly with stimulation Level in a manner predicted by applied RMS. ΔT increases with Level and impedance until stimulator compliance was reached. Therefore, IPG bandwidth and compliance dampen peak heating. Nonetheless, temperature increases predicted by bioheat multi‐physic models (ΔT = 0.64°C and 1.42°C respectively at Level 4 and 7 at the cervical segment; ΔT = 0.68°C and 1.72°C respectively at Level 4 and 7 at the thoracic spinal cord)–within ranges previously reported to effect neurophysiology. Heating of spinal tissues by this 10 kHz SCS system theoretically increases quickly with stimulation level and load impedance, while dampened by IPG pulse bandwidth and voltage compliance limitations. If validated in vivo as a mechanism of kHz SCS, bioheat models informed by IPG limitations allow prediction and optimization of temperature changes.

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Neural Engineering
New Paper: Effects of 6-month at-home transcranial direct current stimulation on cognition and cerebral glucose metabolism in Alzheimer’s disease

Im JJ, Jeong H, Bikson M, Woods AJ, Unal G, Oh JK, Na S, Park, J-S, Knotkova H, Song I-K, Chung Y-A. Effects of 6-month at-home transcranial direct current stimulation on cognition and cerebral glucose metabolism in Alzheimer’s disease. Brain Stimulation 12 (2019) 1222e1228. https://doi.org/10.1016/j.brs.2019.06.003.


Download: PDF published in Brain Stimulation – DOI

Abstract

Although single or multiple sessions of transcranial direct current stimulation (tDCS) on the prefrontal cortex over a few weeks improved cognition in patients with Alzheimer’s disease (AD), effects of repeated tDCS over longer period and underlying neural correlates remain to be elucidated. This study investigated changes in cognitive performances and regional cerebral metabolic rate for glucose (rCMRglc) after administration of prefrontal tDCS over 6 months in early AD patients. Patients with early AD were randomized to receive either active (n = 11) or sham tDCS (n = 7) over the dorsolateral prefrontal cortex (DLPFC) at home every day for 6 months (anode F3/cathode F4, 2 mA for 30 min). All patients underwent neuropsychological tests and brain 18F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) scans at baseline and 6-month follow-up. Changes in cognitive performances and rCMRglc were compared between the two groups. Compared to sham tDCS, active tDCS improved global cognition measured with Mini-Mental State Examination (p for interaction = 0.02) and language function assessed by Boston Naming Test (p for interaction = 0.04), but not delayed recall performance. In addition, active tDCS prevented decreases in executive function at a marginal level (p for interaction < 0.10). rCMRglc in the left middle/inferior temporal gyrus was preserved in the active group, but decreased in the sham group (p for interaction < 0.001). Daily tDCS over the DLPFC for 6 months may improve or stabilize cognition and rCMRglc in AD patients, suggesting the therapeutic potential of repeated at-home tDCS.

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Neural Engineering
New Paper: Antiepileptic Effects of a Novel Non-invasive Neuromodulation Treatment in Early-Onset Epileptic Encephalopathy

Meiron O, Gale R, Namestnic J, Bennet-Back O, Gebodh N, Esmaeilpour Z, Mandzhiyev V and Bikson M (2019) Antiepileptic Effects of a Novel Non-invasive Neuromodulation Treatment in a Subject With Early-Onset Epileptic Encephalopathy: Case Report With 20 Sessions of HD-tDCS Intervention. Front. Neurosci. 13:547. doi: 10.3389/fnins.2019.00547 PDF


Download: PDF published in Frontiers in Neuroscience – DOI

Abstract

The current clinical investigation examined high-definition transcranial direct current stimulation (HD-tDCS) as a focal, non-invasive, anti-epileptic treatment in a child with early-onset epileptic encephalopathy. We investigated the clinical impact of repetitive (20 daily sessions) cathode-centered 4 × 1 HD-tDCS (1 mA, 20 min, 4 mm ring radius) over the dominant seizure-generating cortical zone in a 40-month-old child suffering from a severe neonatal epileptic syndrome known as Ohtahara syndrome (OS). Seizures and epileptiform activity were monitored and quantified using video-EEG over multiple days of baseline, intervention, and post-intervention periods. Primary outcome measures were changes in seizure frequency and duration on the last day of intervention versus the last baseline day, preceding the intervention. In particular, we examined changes in tonic spasms, tonic-myoclonic seizures (TM-S), and myoclonic seizures from baseline to post-intervention. A trend in TM-S frequency was observed indicating a reduction of 73% in TM-S frequency, which was non-significant [t(4) = 2.05, p = 0.1], and denoted a clinically significant change. Myoclonic seizure (M-S) frequency was significantly reduced [t(4) = 3.83, p = 0.019] by 68.42%, compared to baseline, and indicated a significant clinical change as well. A 73% decrease in interictal epileptic discharges (IEDs) frequency was also observed immediately after the intervention period, compared to IED frequency at 3 days prior to intervention. Post-intervention seizure-related peak delta desynchronization was reduced by 57%. Our findings represent a case-specific significant clinical response, reduction in IED, and change in seizure-related delta activity following the application of HD-tDCS. The clinical outcomes, as noted in the current study, encourage the further investigation of this focal, non-invasive neuromodulation procedure in other severe electroclinical syndromes (e.g., West syndrome) and in larger pediatric populations diagnosed with early-onset epileptic encephalopathy.

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Neural Engineering
New Paper: Wearable Cane and App System for Improving Mobility in Toddlers/Pre-schoolers With Visual Impairment

Ambrose-Zaken GV, FallahRad M, Bernstein H, Wall Emerson R and Bikson M (2019) Wearable Cane and App System for Improving Mobility in Toddlers/Pre-schoolers With Visual Impairment. Front. Educ. 4:44. doi: 10.3389/feduc.2019.00044 PDF


Download: PDF published in Frontiers in Education – DOI

Abstract

Children with congenital severe visual impairment and blindness (SVI&B) are at greater risk of developing delays in motor and other developmental domains. This report describes a series of experiments conducted to evaluate a novel wearable cane and mobile application system prototype. The wearable cane and application system was tested on ability to (a) provide hands-free autonomous arc able to detect obstacles, level, and surface changes; (b) integrate into indoor/outdoor activities of a specialized pre-school for learners with SVI&B; and (c) be adopted by families, professionals and learners with SVI&B as a safe mobility solution. Sixteen stakeholders and 34 children under five with SVI&B evaluated the prototype system. The project successfully created a hands-free wearable white cane that provided students with SVI&B under age five with next step warning when walking across a variety of terrain. Pre-school participants with SVI&B easily adopted the wearable cane into their activities with minimal to no prompting or instruction. The P20 prototype scored well across usability features, including maintaining consistent, hands-free, autonomous arc. The invention of a hands-free mobility tool was a significant outcome of this project. These data support that autonomous arc has the ability to provide developmentally appropriate safe mobility solution for toddlers with SVI&B.

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Neural Engineering
Prof. Bikson quoted on HD-tACS for memory in Neurology Today

Neurology Today feature on “A New Study Suggests Non-Invasive Brain Stimulation Can Improve Working Memory” where Dr. Robert M.G. Reinhart and colleagues used High-Definition transcranial Alternating Current Stimulation (HD-tACS) to boost memory in older adults (trial published in Nature). Prof. Marom Bikson quoted as:

“Rather than overriding the network, HD-tACS modulates it,” said Marom Bikson, PhD, a scientist in the department of biomedical engineering at the City College of New York. Dr. Bikson was not directly involved in the study in Nature Neuroscience, but he invented the high-definition stimulation used in the experiments.

Many researchers are using high-definition technology to study the brain,” explained Dr. Bikson. “In this study, the stimulation was designed to reverse the brain’s electrical deficits that they observed in some older adults. A more robust working memory was revived by rhythmically synchronizing brain circuits.”

“They used these tools in a very clever way,” he continued. “They are not claiming that they proved this treatment enhances memory. A lot more work needs to be done, but this study provides support for moving ahead with such clinical trials.”

Read the full article here

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Neural Engineering
BME PhD Defense – Dennis Truong – 05/13/2019

Dennis Truong, Biomedical Engineering doctoral student in Dr. Bikson’s lab will defend his dissertation titled “Translational Modeling of Non-Invasive Electrical Stimulation” on Monday. May 13, 2019 at 11am in the Center for Discovery & Innovation building, room 4.352 (4th floor conference room). All are welcome to attend the public portion.

Abstract
Seminal work in the early 2000’s demonstrated the effect of low amplitude non-invasive electrical stimulation in people using neurophysiological measures (motor evoked potentials, MEPs). Clinical applications of transcranial Direct Current Stimulation (tDCS) have since proliferated, though the mechanisms are not fully understood. Efforts to refine the technique to improve results are on-going as are mechanistic studies both in vivo and in vitro. Volume conduction models are being applied to these areas of research, especially in the design and analysis of clinical montages. However, additional research on the parameterization of models remains.
In this dissertation, Finite Element Method (FEM) models of current flow were developed for clinical applications. The first image-derived models of obese subjects were developed to assess the relative impact of fat delineation from skin. Body mass index and more broadly inter-individual differences were considered. The effect of incorporating the meninges was predicted from CAD-based (Computer Aided Design) models before being translated into image-derived head models as an “emulated” CSF conductivity. These predictions were tested in a recently validated database of head models. Multi-scale models of transcutaneous vagus nerve stimulation (tVNS) were developed by coupling image-derived volume conduction models with physiological compartment modeling. The impact of local tissue inhomogeneities on fiber activation were considered.

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Neural Engineering
Special Neural Engineering Seminar: Flavio Frohlich (Tuesday March 26 at 2 pm)

Title: Brain Oscillations: Next Therapeutic Frontier?

Speaker: Dr. Flavio Frohlich, Associate Professor, The University of North Carolina (UNC) School of Medicine

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When: Tuesday, March 26, 2019 at 2 pm

Where: CCNY Center for Discovery and Innovation, 3rd floor seminar room (CDI 3.352)

Contact: Greg Kronberg (gregkronberg@gmail.com, 212-650-8876) for access to CDI building

Abstract:

Electrical activity in brain networks exhibits rhythmic structure. These brain oscillations are impaired in both neurological and psychiatric illnesses. Over the last few years, we have learned that such oscillatory dynamics are surprisingly susceptible to weak but smartly timed perturbations. In my talk, I will show how we draw from engineering, biology, and medicine to develop new therapeutic strategies that leverage this fundamental response property of neuronal networks. I will outline how the integration of target identification, target engagement, and target validation provides a framework for the rational design of brain stimulation paradigms that target and restore brain oscillations. By combining computational modeling, preclinical animal research, and human clinical trials, we are on a long but very exciting journey towards revolutionizing how we treat brain disorders. Join us for the journey!

Neural Engineering
New Paper: Topical Review: Electrophysiology equipment for reliable study of kHz electrical stimulation

FallahRad M, Zannou AL, Khadka N, Prescott SA, Ratte S, Zhang T, Esteller R, Hershey B, Bikson M. Topical Review: Electrophysiology equipment for reliable study of kHz electrical stimulation. The Journal of Physiology. PDF


Download: PDF published in The Journal of Physiology- DOI

Abstract

Characterizing the cellular targets of kHz (1–10 kHz) electrical stimulation remains a pressing topic in neuromodulation because expanding interest in clinical application of kHz stimulation has surpassed mechanistic understanding. The presumed cellular targets of brain stimulation do not respond to kHz frequencies according to conventional electrophysiology theory. Specifically, the low‐pass characteristics of cell membranes are predicted to render kHz stimulation inert, especially given the use of limited‐duty‐cycle biphasic pulses. Precisely because kHz frequencies are considered supra‐physiological, conventional instruments designed for neurophysiological studies such as stimulators, amplifiers, and recording microelectrodes do not operate reliably at these high rates. Moreover, for pulsed waveforms, the signal frequency content is well above the pulse repetition rate. Thus, the very tools used to characterize the effects of kHz electrical stimulation may themselves be confounding factors. We illustrate custom equipment design that supports reliable electrophysiological recording during kHz‐rate stimulation. Given the increased importance of kHz stimulation in clinical domains and compelling possibilities that mechanisms of actions may reflect yet undiscovered neurophysiological phenomena, attention to suitable performance of electrophysiological equipment is pivotal.

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Neural Engineering
New Paper: Prevention of schizophrenia deficits via non-invasive adolescent frontal cortex stimulation in rats

Hadar R, Winter R, Callesen HE, Wieske F, Habelt B, Khadka N, Felgel-Farnholz V, Barroeta-Hlusicka E, Reis J, Tatarau CA, Funke K, Fritsch B, Bernhardt N, Bikson M, Nitsche MA, Winter C. 2018. Prevention of schizophrenia deficits via non-invasive adolescent frontal cortex stimulation in rats. Nature Molecular Psychiatry. 2019. https://doi.org/10.1038/s41380-019-0356-x. PDF


Download: PDF published in Nature Molecular Psychiatry – DOI

Abstract

Schizophrenia is a severe neurodevelopmental psychiatric affliction manifested behaviorally at late adolescence/early adulthood. Current treatments comprise antipsychotics which act solely symptomatic, are limited in their effectiveness and often associated with side-effects. We here report that application of non-invasive transcranial direct current stimulation (tDCS) during adolescence, prior to schizophrenia-relevant behavioral manifestation, prevents the development of positive symptoms and related neurobiological alterations in the maternal immune stimulation (MIS) model of schizophrenia.

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Neural Engineering
Special Neural Engineering Seminar: Maria Ironside (Friday Feb. 1st at 1 pm)

Title: Neurocognitive mechanisms of DLPFC tDCS in major depressive disorder

Speaker: Dr. Maria Ironside, Post Doctoral Research Fellow, Center for Depression, Anxiety and Stress Research, McLean Hospital – Harvard Medical School


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When: Friday Feb. 1 2019 at 1 pm

Where: CCNY Center for Discovery and Innovation, 4th floor seminar room (CDI 4.352)

Contact: Greg Kronberg (gregkronberg@gmail.com, 212-650-8876) for access to CDI building

Abstract:

The difficulty in treating mood and anxiety disorders has sparked clinical interest in novel treatments, such as transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC). However, underlying mechanisms of action are unclear. It is established that people with mood and anxiety disorders have negative cognitive biases, such as increased vigilance to threat. Psychiatric treatments have acute effects on these cognitive biases which predict later therapeutic action. Such effects are proposed as cognitive biomarkers of response.

A healthy volunteer investigation revealed an anxiolytic like effect (reduced threat vigilance) of a single session of tDCS on a behavioural test of proven clinical relevance (Ironside et al., 2016, Biological Psychiatry). Complementing these data, we used functional imaging to reveal that, in a sample of trait anxious females, tDCS of the DLPFC increased activation in an attentional control network and reduced amygdala response to fearful face distractors (Ironside et al., 2018, JAMA Psychiatry). This provides causal evidence that modulating activity in the DLPFC inhibits amygdala response to threat, providing a potential neural mechanism for the previous reduction in vigilance to threat. Collectively, these results propose an emerging neurocognitive model for the mechanisms of action of tDCS. We also examined pairing tDCS with attentional bias modification training and found no effect of stimulation.

Together, findings point to an anxiolytic-like effect of DLPFC tDCS on cognitive and neural biomarkers relevant to mood and anxiety disorders, indicating potential cognitive and underlying neural mechanisms that may mediate the reported clinical efficacy of DLPFC tDCS. This has implications as the identification of treatment response markers could aid patient selection for future trials and ultimately treatment selection for patients.

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Neural Engineering
Read all Neural Engineering Lab Preceedings & Abstracts from NYC/NANS 2019!
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Adair, Devin, Dennis Q. Truong, Libby Ho, Bashar W. Badran, Helen Borges, and Marom Bikson. 2019. Abstract #124: How to modulate cognition with cranial nerve stimulation? Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e42-3, https://doi.org/10.1016/j.brs.2018.12.131.

Bikson, M. 2019. Downloading personalized brain stimulation. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): 424, https://doi.org/10.1016/j.brs.2018.12.375.

Chhatbar, Pratik Y., Steven A. Kautz, Istvan Takacs, Nathan C. Rowland, Gonzalo J. Revuelta, Mark S. George, Marom Bikson, and Wuwei Feng. 2019. Abstract #22: First report of recording transcranial direct current stimulation-generated electric fields in subthalamic nuclei using directional leads. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e8, https://doi.org/10.1016/j.brs.2018.12.029.

DaFonseca, Estevão, Alexandre F. DaSilva, Marom Bikson, Dennis Troung, and Marcos F. DosSantos. 2019. Proceedings #21: Specific patterns of current flow generated by different tDCS montages in the midbrain and in the trigeminal brainstem sensory nuclear complex. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e84-6, https://doi.org/10.1016/j.brs.2018.12.190.

Datta, Abhishek, Yu Huang, Chris Thomas, Marom Bikson, and Ahmed Duke Shereen. 2019. Proceedings #12: Influence of incorporating electrode information from MR images: Towards building more realistic forward models. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e72-4, https://doi.org/10.1016/j.brs.2018.12.181.

Esmaeilpour, Z., M. Jackson, G. Kronberg, T. Zhang, R. Esteller, B. Hershey, and M. Bikson. 2019. Effect of kHz electrical stimulation on hippocampal brain slice excitability and network dynamics. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): 586, https://doi.org/10.1016/j.brs.2018.12.948.

Esmaeilpour, Zeinab, Ahmed Duke Shereen, Marom Bikson, and Hamed Ekhtiari. 2019. Abstract #147: MRI neuroimaging methods for tDCS: A methodological note on study design and parameter space. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e50, https://doi.org/10.1016/j.brs.2018.12.154.

Fallahrad, Mohamad, Louis Zannou, Niranjan Khadka, Steven A. Prescott, Stéphanie Ratté, Tianhe Zhang, Rosana Esteller, Brad Hershey, and Marom Bikson. 2019. Abstract #159: Hardware suitable for electrophysiology and stimulation in kHz range. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e54, https://doi.org/10.1016/j.brs.2018.12.166.

Favoretto, Diandra B., Eduardo Bergonzoni, Diego Nascimento, Brunna Rimoli, Tenysson Will-Lemos, Dennis Q. Truong, Renato Moraes, et al. 2019. Abstract #119: Polarity-dependent effects on postural control after high-definition transcranial direct current stimulation over the temporo-parietal junction. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e41, https://doi.org/10.1016/j.brs.2018.12.126.

Fonteneau, Clara, Marine Mondino, Martijn Arns, Chris Baeken, Marom Bikson, Andre R. Brunoni, Matthew J. Burke, et al. Sham tDCS: A hidden source of variability? reflections for further blinded, controlled trials. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation (2019/01), https://doi.org/10.1016/j.brs.2018.12.977.

Gebodh, Nigel, Zeinab Esmaeilpour, Devin Adair, Kenneth Chelette, Jacek Dmochowski, Lucas Parra, Adam J. Woods, Emily S. Kappenman, and Marom Bikson. 2019. Abstract #125: Failure of conventional signal processing techniques to remove “Physiological” artifacts from EEG during tDCS. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e43, https://doi.org/10.1016/j.brs.2018.12.132.

Gebodh, Nigel, Laura Vacchi, Devin Adair, Gozde Unal, Alexander Poltorak, Valeria Poltorak, and Marom Bikson. 2019. Proceedings #11: Replay of endogenous sleep rhythms to produce sleepiness. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e71-2, https://doi.org/10.1016/j.brs.2018.12.180.

Huang, Y., A. Datta, M. Bikson, and L. Parra. 2019. ROAST: A fully-automated, open-source, realistic vOlumetric-approach-based simulator for TES. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): 391, https://doi.org/10.1016/j.brs.2018.12.253.

Huang, Y., and L. Parra. 2019. Deep brain areas can be reached by transcranial electric stimulation with multiple electrodes. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): 390-1, https://doi.org/10.1016/j.brs.2018.12.252.

Huang, Yu, Chris Thomas, Abhishek Datta, and Lucas C. Parra. 2019. Proceedings #23: Inaccurate segmentation of lesioned brains can significantly affect targeted transcranial electrical stimulation on stroke patients. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e87-9, https://doi.org/10.1016/j.brs.2018.12.192.

Jiang, Jimmy, Dennis Q. Truong, and Marom Bikson. 2019. Abstract #115: What is theoretically more focal: HD-tDCS or TMS? Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e39-40, https://doi.org/10.1016/j.brs.2018.12.122.

Jiang, Jimmy, Dennis Q. Truong, Yu Huang, Lucas Parra, and Marom Bikson. 2019. Abstract #118: Transcranial electrical stimulation models using an emulated-CSF value approximate the meninges more accurately. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e40-1, https://doi.org/10.1016/j.brs.2018.12.125.

Khadka, N., A. Zannou, D. Truong, T. Zhang, R. Esteller, B. Hersey, and M. Bikson. 2019. Generation 2 kilohertz spinal cord stimulation (kHz-SCS) bioheat multi-physics model. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): 566, https://doi.org/10.1016/j.brs.2018.12.876.

Khadka, Niranjan, Helen Borges, Trynia Kauffman, Alain Pascal, Bhaskar Paneri, Electra Nassis, Yungjae Shin, et al. 2019. Abstract #109: Tolerability of an adaptive-tDCS upto 4 mA using subject assessment and machine-learning to optimize dose. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e37-8, https://doi.org/10.1016/j.brs.2018.12.116.

Khadka, Niranjan, Helen Borges, Adantchede L. Zannou, Jongmin Jang, Byungjik Kim, Kiwon Lee, and Marom Bikson. 2019. Abstract #100: Dry tDCS: Tolerability of a novel multilayer hydrogel composite non-adhesive electrode for tDCS. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e35, https://doi.org/10.1016/j.brs.2018.12.107.

Kronberg, G., A. Rahman, M. Bikson, and L. Parra. 2019. A hebbian framework for predicting modulation of synaptic plasticity with tDCS. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): 554, https://doi.org/10.1016/j.brs.2018.12.831.

Kronberg, Greg, Asif Rahman, Marom Bikson, and Lucas Parra. 2019. Abstract #122: A hebbian framework for predicting modulation of synaptic plasticity with tDCS. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e42, https://doi.org/10.1016/j.brs.2018.12.129.

Louviot, Samuel, Jacek Dmochowski, Jacques Jonas, Louis Maillard, Sophie Colnat-Coulbois, Louise Tyvaert, and Laurent Koessler. 2019. Abstract #32: Medial and lateral temporal lobe neuromodulation in epilepsy: A simultaneous tdcs-seeg investigation. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e12, https://doi.org/10.1016/j.brs.2018.12.039.

Louviot, Samuel, Jacek Dmochowski, Jacques Jonas, Louis Maillard, Sophie Colnat-Coulbois, Louise Tyvaert, and Laurent koessler. 2019. Abstract #68: A human in-vivo evaluation of roast using simultaneous intracerebral electrical stimulations and scalp eeg. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e24, https://doi.org/10.1016/j.brs.2018.12.075.

Lucas Parra, Yu Huang. 2019. Abstract #38: Transcranial electric stimulation with multiple electrodes can reach deep brain areas. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e14, https://doi.org/10.1016/j.brs.2018.12.045.

Meiron, Oded, Rena Gale, Julia Namestnic, Odeya Bennet-Back, Jonathan David, Nigel Gebodh, Devin Adair, Zeinab Esmaeilpour, and Marom Bikson. 2019. Abstract #123: Attenuation of pathological EEG features in nonatal electroclinical syndromes: HD-tDCS in catastrophic epilepsies. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e42, https://doi.org/10.1016/j.brs.2018.12.130.

Mourdoukoutas, Antonios, Gozde Unal, John Martin, Mar Cortes, Jeremy Fidock, and Marom Bikson. 2019. Proceedings #14: Neuromodulation of spinal cord with tDCS extracephalic return electrode. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e75-6, https://doi.org/10.1016/j.brs.2018.12.183.

Quinn, Davin, Joel Upston, Thomas Jones, Jessica Richardson, Lindsay Worth, Violet Fratzke, Julia Stephen, et al. 2019. Abstract #1: Individualizing HD-tDCS with fMRI and E-field modeling: Pilot data from the NAVIGATE-TBI study. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e1, https://doi.org/10.1016/j.brs.2018.12.008.

Salvi, Carola, Ryan D. Conrardy, Marom Bikson, Mark Beeman, and Jordan Grafman. 2019. Abstract #142: Effects of high definition tDCS on problem solving networks. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e49, https://doi.org/10.1016/j.brs.2018.12.149.

Shaw, M., N. Pawlak, C. Choi, N. Khan, A. Datta, and M. Bikson. 2019. Transcranial direct current stimulation (tDCS) induces acute changes in brain metabolism. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): 518, https://doi.org/10.1016/j.brs.2018.12.703.

Shereen, D., and L. Parra. 2019. Rapid measurement of electromagnetic fields induced from transcranial electric stimulation using magnetic resonance imaging. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): 584, https://doi.org/10.1016/j.brs.2018.12.938.

Shereen, Duke, and Lucas Parra. 2019. Abstract #98: Rapid field mapping using magnetic resonance imaging during transcranial direct current stimulation. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e34, https://doi.org/10.1016/j.brs.2018.12.105.

Tarbell, John, Marom Bikson, Limary M. Cancel, and Niranjan Khadka. 2019. Abstract #33: Direct current stimulation of endothelial monolayers induces an increase in transport by the electroosmotic effect. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e12, https://doi.org/10.1016/j.brs.2018.12.040.

Trapp, Nicholas T., Willa Xiong, Britt M. Gott, Gemma D. Espejo, Marom Bikson, and Charles R. Conway. 2019. Proceedings #51: 4 mA adaptive transcranial direct current stimulation for treatment-resistant depression: Early demonstration of feasibility with a 20-session course. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e124-5, https://doi.org/10.1016/j.brs.2018.12.220.

Truong, Dennis Q., Catherine Maglione, Yishai Valter, Louis Zannou, A. D. Shereen, Preston Williams, John H. Martin, and Marom Bikson. 2019. Abstract #29: Scaling spinal cord injury models for non-invasive stimulation. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e10-1, https://doi.org/10.1016/j.brs.2018.12.036.

Unal, Gozde, Bronte N. Ficek, Kimberly T. Webster, Syed Shahabuddin, Dennis Q. Truong, Marom Bikson, and Kyrana Tsapkini. 2019. Abstract #113: Individualized modeling for subjects with primary progressive aphasia. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e39, https://doi.org/10.1016/j.brs.2018.12.120.

Valero-Cabre, Antoni, Clara Sanches, Dennis Q. Truong, Marom Bikson, and Marc Teichmann. 2019. Abstract #2: Improvement of language function following prefrontal transcranial direct current brain stimulation in progressive supranuclear palsy. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e1-2, https://doi.org/10.1016/j.brs.2018.12.009.

Williams, Preston, John Brandenburg, Dennis Q. Truong, Alan C. Seifert, Adrish Sarkar, Junqian Xu, Marom Bikson, and John Martin. 2019. Abstract #136: Translational neuromodulation of motor-output using trans-spinal direct current stimulation (tsDCS) in a large animal model. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e46-7, https://doi.org/10.1016/j.brs.2018.12.143.

Zannou, Adantchede L., Niranjan Khadka, Mohamad FallahRad, Dennis Truong, and Marom Bikson. 2019. Abstract #30: Tissue temperature increases by HF10 senza spinal cord stimulation system: Phantom and bioheat model. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e11, https://doi.org/10.1016/j.brs.2018.12.037.

Neural Engineering
New Paper – Sham tDCS: A hidden source of variability Reflections for further blinded, controlled trials

Fonteneau C, Mondino M, Arns M, Baeken C, Bikson M, Brunoni AR, Burke MJ, Neuvonen T, Padberg F, Pascual-Leone A, Poulet E, Ruffini G, Santarnecchi E, Sauvaget A, Schellhorn K, Suaud-Chagny M-F, Palm U, Brunelin J. Sham tDCS: a hidden source of variability? Reflections for further blinded, controlled trials. Brain Stimulation. https://doi.org/10.1016/j.brs.2018.12.977 (In Press). 2019


Download: PDF published in Brain Stimulation – DOI

Abstract
Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique increasingly used to modulate neural activity in the living brain. In order to establish the neurophysiological, cognitive or clinical effects of tDCS, most studies compare the effects of active tDCS to those observed with a sham tDCS intervention. In most cases, sham tDCS consists in delivering an active stimulation for a few seconds to mimic the sensations observed with active tDCS and keep participants blind to the intervention. However, to date, sham-controlled tDCS studies yield inconsistent results, which might arise in part from sham inconsistencies. Indeed, a multiplicity of sham stimulation protocols is being used in the tDCS research field and might have different biological effects beyond the intended transient sensations. Here, we seek to enlighten the scientific community to this possible confounding factor in order to increase reproducibility of neurophysiological, cognitive and clinical tDCS studies.

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Neural Engineering