Nasimova, M., Khadka, N. & Bikson, M. Computational modeling of neuromuscular activation by transcutaneous electrical nerve stimulation to the lower back. Biomed. Phys. Eng. Express 11, 035004 (2025). PDF

Abstract

Objectives: Transcutaneous Electrical Nerve Stimulation (TENS) to the lower back is an established electrical therapy for acute and chronic back pain. The efficacy and mechanisms of lower back TENS depend on the penetration depth of electrical current. We compare the intensity and spatial extent (depth) of current flow in the body during TENS with varied electrode positions/shapes on the human back.
Materials and Methods: A high-resolution MRI-derived anatomical model of the back was developed, considering major tissue compartments, including skin and muscles. TENS with upper and lower back electrode positions and varied electrode shapes (square, circular, rectangular) were simulated. An exemplary 50 mA current was applied under quasistatic approximation and quasiuniform electric field assumption of 6.15 V m−1 (low), 12.3 V m−1 (mid), and 24.6 V m−1 (high) neuromuscular activation thresholds were considered.

Results: Under all simulated TENS conditions (50 mA), electric fields at the skin exceed the high threshold (consistent with peripheral nerve activation) and at least some muscle regions exceed the mid threshold. Muscle activation was influenced by the anatomy of muscle in the medial-lateral direction and upper-lower back. The electrode shape had minimal effect on deep tissue current penetration.
Conclusions: Our simulations indicate significant current penetration into back tissue (electric fields above low threshold) to >8 cm in all TENS conditions simulated, consistent with nerve and muscle activation.
Significance: Anatomically precise models of upper and lower back TENS show current penetration to deep muscle, supporting direct muscle stimulation driving clinical benefits.

Brain Stimulation, Volume 18, Issue 2p280-286 March-April, 2025

Statistical method accounts for microscopic electric field distortions around neurons when simulating activation thresholds

Konstantin Weisea ∙ Sergey N. Makaroff∙ Ole Numssen∙ Marom Bikson ∙ Thomas R. Knöscheb

Journal link. PDF.

Highlights

• Microscopic field inhomogeneity alters neuron activation in neuromodulation models.

• Classical models miss the impact of brain microstructure on electric field effects.

• A novel statistical approach improves prediction of TMS neuronal activation thresholds.

• The results match experimental TMS thresholds, improving model predictions.

Abstract

Introduction

Notwithstanding advances in computational models of neuromodulation, there are mismatches between simulated and experimental activation thresholds. Transcranial Magnetic Stimulation (TMS) of the primary motor cortex generates motor evoked potentials (MEPs). At the threshold of MEP generation, whole-head models predict macroscopic (at millimeter scale) electric fields (50–70 V/m) which are considerably below conventionally simulated cortical neuron thresholds (175–350 V/m).

Methods

We hypothesize that this apparent contradiction is in part a consequence of electrical field warping by brain microstructure. Classical neuronal models ignore the physical presence of neighboring neurons and microstructure and assume that the macroscopic field directly acts on the neurons. In previous work, we performed advanced numerical calculations considering realistic microscopic compartments (e.g., cells, blood vessels), resulting in locally inhomogeneous (micrometer scale) electric field and altered neuronal activation thresholds. Here we combine detailed neural threshold simulations under homogeneous field assumptions with microscopic field calculations, leveraging a novel statistical approach.

Results

We show that, provided brain-region specific microstructure metrics, a single statistically derived scaling factor between microscopic and macroscopic electric fields can be applied in predicting neuronal thresholds. For the cortical sample considered, the statistical method matches TMS experimental thresholds.

Conclusions

Our approach can be broadly applied to neuromodulation models, where fully coupled microstructure scale simulations may not be computationally tractable.

The 6th International Brain Stimulation Conference (Kobe, Japan), Feb 23-26, 2025. Full program.

09:00-17:00 Sunday, 23 February, 2025, 301 KICC Brain Stimulation at the Microscopic Scale: Multiscale Models and Cellular Studies PreCon. 4:00PM - 4:25PM Gregory Noetscher and Marom Bikson (WPI, CCNY, USA) - Microvascular modulation of brain stimulation with realistic large microvascular networks

08:30-10:30 Monday, 24 February, 2025, Portopia Hall Plenary Lectures. 09:00-9:45: [PL01] Marom Bikson, Wearable Disposable Brain Stimulation. slides PDF

Poster Session 1. 12:45-13:45 Monday, 24 February, 2025, Ohwada & Ohwada Foyer P1.095 Long-term effect of tDCS plus cognitive training in the quality of life of patients with Post-Acute Sequelae of SARS-CoV-2 (PASC): a randomized, double-blind, controlled trial Kallene S Vidal, Adriano Domingos-Neto, Beatriz Cavendish, Bianca Pinto, Mariana Batista, Pedro Silva, Alisson Lima, Rebeca Pelosof, Juliana Pereira, Stephan Goerigk, Leigh Chavert, Marom Bikson, Andre Brunoni

Poster Session 1. 12:45-13:45 Monday, 24 February, 2025.P3.122 High-Capacity tDCS in Bench-top and Wearable Platforms Kyle Donnery, Mohamad FallahRad, Mojtaba Belali Koochesfahani, Marom Bikson

16:00-18:00 Tuesday, 25 February, 2025, Ohwada Room On Demand Poster Symposium Session 3 ODS5.18 16:25-16:26 Wearable disposable transcranial direct current stimulation Marom Bikson

Leigh Charvet, Judith D. Goldberg, Xiaochun Li, Pamela Best, Matthew Lustberg, Michael Shaw, Lana Zhovtis, Josef Gutman, Abhishek Datta, Marom Bikson, Giuseppina Pilloni. Lauren Krupp. (2025) Home-based transcranial direct current stimulation paired with cognitive training to reduce fatigue in multiple sclerosis. Scientific Reports 15:: 4551 DOI: https://doi.org/10.1038/s41598-025-88255-2

PDF

Abstract: Fatigue is a common and often debilitating feature of multiple sclerosis (MS) that lacks reliably

effective treatment options for most patients. Transcranial direct current stimulation (tDCS), a safe and

well-tolerated type of noninvasive brain stimulation, is a low-cost and home-based approach with the

potential to reduce fatigue in MS. We conducted a double-blind, sham-controlled, randomized clinical

trial to compare active vs. low-dose (sham) tDCS paired with computer-based cognitive training,

delivered as a home-based intervention, to reduce MS-related fatigue. Participants with MS-related

fatigue, but without depression, were stratified by neurologic disability using the Extended Disability

Status Scale (EDSS) and randomized to complete 30 daily sessions over six weeks of either active or

sham tDCS paired with online cognitive training (BrainHQ). The primary outcome was the change in

PROMIS Fatigue score from baseline to the end of the intervention. A total of 117 participants were

randomized, with 92% completing all treatment sessions. Both groups showed significant reductions

in fatigue, with no significant difference between them. This suggests that tDCS does not provide any

additional benefit over cognitive training alone in reducing fatigue, but confirms the feasibility and

tolerance of this home-based intervention.

Neural Prosthesis Seminar co-hosted with CWRU BME Seminar on February 13th at 12PM.

Dr. Marom Bikson, Case Alumnus and Professor of Biomedical Engineering, CCNY

Title: Wearable Disposable Electrical Stimulation

Time: 12PM - 1PM

Location: CWRU - Wickenden: Room 321

Livestream: https://case.edu/livestream/fes

Abstract: Electrical stimulation devices are becoming compoundingly complex. However, to democratize electrotherapy, devices should instead be cheap and easy to use - more like pharmacotherapy. Wearable Disposable Electrical Stimulation is a fundamental new electrochemical technology platform using no electronic components. Rather devices are formed from a novel printable manufacturing based on abundant, environmentally-benign, safe materials. Application-specific prescribed electrical discharge is delivered in a disposable band-aid form factor (~1 mm thick, in any flexible planar shape). Devices are single use: auto-discharging upon application and disposable. Thus, while all conventional electrical stimulation devices use an independent power source and electronics, and require connecting accessories and programming at each use, our design eliminates these steps. At scale, the cost-of-goods approaches that of a drug tablet. We envision a future where indication-specific versions of Wearable Disposable Electrical Stimulation are distributed at pharmacies alongside drugs and topical creams. Where patients can carry a therapy dose folded in their pocket and discreetly apply it whenever needed.

Event calendar invite https://www.addevent.com/event/ji24658745

Based on this preprint: https://www.biorxiv.org/content/10.1101/2023.11.28.569062v3

At the North American Neuromodulation Society (NANS) 2025 meeting, Dr. Marom Bikson will present on Subthreshold Mechanisms of Brain and Spinal Cord Stimulation (Jan 30, 2025 in the Engineering Pre-Con")

Slides PDF

Dr. Bikson also served as scientific co-chair of the NANS 2025 program, and on the NANS board.

A new lab paper in Brain Stimulation Journal challenges a foundational assumption in computational models of brain stimulation (neuromodulation/electrical stimulation). Rather than suggest prior predictions were wrong, this paper shows how the suitability of this foundational assumption can be evaluated in any application (FES, SCS, DBS, TMS, tDCS, tACS, ETC, TI...). So this will be interesting...

"Enabling electric field model of microscopically realistic brain" is 1) First to model brain stimulation with a realistic microscopic extracellular environment; 2) Showing microscopic perturbations of the electric field by neighboring cell structures; 3) Applicable to all electrical/magnetic stimulation.

This pipeline contrasts with decades of convention which: a) First ignores all microscopic structures, with each region represented by a macroscopically averaged resistivity; b) Only after the macroscopic electric field is predicted (with FEM) are isolated neurons “reinserted” to model their response. Justified or not, this convention is universal from classical modeling studies to the most advanced recent studies because it was *computationally necessary*. The reliability of this convention depends on the physical presence of cellular structures (such as neurons, glia, vessels) NOT impacting the generation of electric fields in the first place. This idea is challenged by the sheer packing of cells - as quantified by scanning electron microscopy.

For the stimulation conditions & limited structures considered in this first study, electric fields were microscopically perturbed by neighboring cells but this only modestly influenced stimulation thresholds (~10%). This provides tentative support that the foundational modeling assumption that ignores the physical presence of neurons is sufficiently precise. But there remain many stimulation technologies (specialty waveforms) & brain structures (blood vessels, synaptic clefts) to consider. This paper provides the pipeline for such ongoing research.

Reference: Zhen Qi, Gregory M Noetscher, Alton Miles, Konstantin Weise, Thomas R Knösche, Cameron R Cadman, Alina R Potashinsky, Kelu Liu, William A Wartman, Guillermo Nunez Ponasso, Marom Bikson, Hanbing Lu, Zhi-De Deng, Aapo R Nummenmaa, Sergey N Makaroff. Enabling electric field model of microscopically realistic brain. Brain Stimulation. 18(1):77-93. doi: 10.1016/j.brs.2024.12.1192

Prof. Marom Bikson was awarded Gold Electrode Award for Neurotechnolgy Researcher of the Year . The award was announced at the 2024 Neurotech Leaders Forum, which took place in November 2024 in San Francisco. The awards were selected by the editors of Neurotech Reports.

Slowing Cognitive Decline in Major Depressive Disorder and Mild Cognitive Impairment A Randomized Clinical Trial

JAMA Psychiatry . 2024 Oct 30:e243241. doi: 10.1001/jamapsychiatry.2024.3241.

Tarek K Rajji 1 2 3, Christopher R Bowie 1 4, Nathan Herrmann 2 5, Bruce G Pollock 1 2, Krista L Lanctôt 2 5, Sanjeev Kumar 1 2, Alastair J Flint 2 6, Linda Mah 2 7, Corinne E Fischer 2 8, Meryl A Butters 9, Marom Bikson 10, James L Kennedy 1 2, Daniel M Blumberger 1 2, Zafiris J Daskalakis 11, Damien Gallagher 2 5, Mark J Rapoport 2 5, Nicolaas P L G Paul Verhoeff 2 7, Angela C Golas 1 2, Ariel Graff-Guerrero 1 2, Erica Vieira 1 2, Aristotle N Voineskos 1 2, Heather Brooks 1, Ashley Melichercik 1, Kevin E Thorpe 12, Benoit H Mulsant 1 2 9; PACt-MD Study Group

Affiliations

• 1 Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.

• 2 Department of Psychiatry and Toronto Dementia Research Alliance, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.

• 3 University of Texas Southwestern Medical Center, Dallas.

• 4 Department of Psychology, Queen's University, Kingston, Ontario, Canada.

• 5 Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.

• 6 University Health Network, Toronto, Ontario, Canada.

• 7 Baycrest Health Sciences, Toronto, Ontario, Canada.

• 8 Keenan Research for Biomedical Science, Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, Ontario, Canada.

• 9 Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania.

• 10 Department of Biomedical Engineering, The City College of New York, New York.

• 11 Department of Psychiatry, University of California, San Diego, La Jolla.

• 12 Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.

JAMA Psychiatry. Published online October 30, 2024. doi:10.1001/jamapsychiatry.2024.3241

Key Points

Question  Does cognitive remediation (CR) plus transcranial direct current stimulation (tDCS) slow cognitive decline in older adults with remitted major depressive disorder (rMDD) or mild cognitive impairment (MCI)?

Findings  In this randomized clinical trial including 375 participants with rMDD or MCI, those randomized to receive active CR plus active tDCS experienced a slower cognitive decline over a median follow-up of 4 years than those randomized to receive sham-plus-sham treatments. The effects were more prominent in the rMDD (with or without MCI) than in the MCI without rMDD group.

Meaning  The treatment of CR plus tDCS is effective in slowing cognitive decline in older adults with rMDD.

Abstract

Importance  Older adults with major depressive disorder (MDD) or mild cognitive impairment (MCI) are at high risk for cognitive decline.

Objective  To assess the efficacy of cognitive remediation (CR) plus transcranial direct current stimulation (tDCS) targeting the prefrontal cortex in slowing cognitive decline, acutely improving cognition, and reducing progression to MCI or dementia in older adults with remitted MDD (rMDD), MCI, or both.

Design, Setting, and Participants  This randomized clinical trial was conducted at 5 academic hospitals in Toronto, Ontario, Canada. Participants were older adults who had rMDD (with or without MCI, age ≥65 y) or MCI without rMDD (age ≥60 y). Assessments were made at baseline, month 2, and yearly from baseline for 3 to 7 years.

Interventions  CR plus tDCS (hereafter, active) or sham plus sham 5 days a week for 8 weeks followed by twice-a-year 5-day boosters and daily at-home CR or sham CR.

Main Outcomes and Measures  The primary outcome was change in global composite cognitive score. Secondary outcomes included changes in 6 cognitive domains, moderating effect of the diagnosis, moderating effect of APOE ε4 status, change in composite score at month 2, and progression to MCI or dementia over time.

Results  Of 486 older adults who provided consent, 375 (with rMDD, MCI, or both) received at least 1 intervention session (mean [SD] age, 72.2 [6.4] years; 232 women [62%] and 143 men [38%]). Over a median follow-up of 48.3 months (range, 2.1-85.9), CR and tDCS slowed cognitive decline in older adults with rMDD or MCI (adjusted z score difference [active − sham] at month 60, 0.21; 95% CI, 0.07 to 0.35; likelihood ratio test [LRT] P = .006). In the preplanned primary analysis, CR and tDCS did not improve cognition acutely (adjusted z score difference [active − sham] at month 2, 0.06, 95% CI, −0.006 to 0.12). Similarly, the effect of CR and tDCS on delaying progression from normal cognition to MCI or MCI to dementia was weak and not significant (hazard ratio, 0.66; 95% CI, 0.40 to 1.08; P = .10). Preplanned analyses showed treatment effects for executive function (LRT P = .04) and verbal memory (LRT P = .02) and interactions with diagnosis (P = .01) and APOE ε4 (P < .001) demonstrating a larger effect among those with rMDD and in noncarriers of APOE ε4.

Conclusions and Relevance  The study showed that CR and tDCS, both targeting the prefrontal cortex, is efficacious in slowing cognitive decline in older adults at risk of cognitive decline, particularly those with rMDD (with or without MCI) and in those at low genetic risk for Alzheimer disease.

Trial Registration  ClinicalTrials.gov Identifier: NCT02386670

Prof. Marom Bikson presents at the International Meeting on Temporal Interference Brain Stimulation on Sep 25-26, 2024 in London UK. Event webstie.

Dr. Bikson speaks on “Biophysical Foundations of Temporal Interference Stimulation”

Slides PDF

New lab publication:

Khadka, Niranjan PhD; Deng, Zhi-De PhD†; Lisanby, Sarah H. MD; Bikson, Marom PhD; Camprodon, Joan A. MD, PhD. Computational Models of High-Definition Electroconvulsive Therapy for Focal or Multitargeting Treatment. The Journal of ECT ():10.1097/YCT.0000000000001069, August 26, 2024. | DOI: 10.1097/YCT.0000000000001069 PDF

A Visual and Narrative Timeline Review of Spinal Cord Stimulation Technology and US Food and Drug Administration Milestones Johnson S. Ho, MD ; Cynthia Poon, MS ; Richard North, MD; William Grubb; Scott Lempka, PhD; Marom Bikson, PhD. Volume 27, Issue 6 , August 2024, Pages 1020-1025

Neuromodulation: Technology at the Neural Interface https://doi.org/10.1016/j.neurom.2024.05.006

PDF

Quasistatic approximation in neuromodulation.

Wang B, Peterchev AV, Gaugain G, Ilmoniemi RJ, Grill WM, Bikson M, Nikolayev D.

J Neural Eng. 2024 Jul 24;21(4). doi: 10.1088/1741-2552/ad625e. PMID: 38994790

PDF

New publication:

Muccio M, Pilloni G, Walton Masters L, He P, Krupp L, Datta A, Bikson M, Charvet L and Ge Y (2024) Simultaneous and cumulative effects of tDCS on cerebral metabolic rate of oxygen in multiple sclerosis. Front. Hum. Neurosci. 18:1418647. doi: 10.3389/fnhum.2024.1418647

Link PDF

Abstract:

Introduction: Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique with simultaneous (during stimulation) and cumulative effects (after repeated sessions) on blood flow and neuronal metabolism. These effects remain mostly unclear especially in multiple sclerosis (MS). This work aims to elucidate brain metabolic and hemodynamic underpinnings of tDCS and its potential therapeutic impact in MS patients using quantitative tDCS-MRI.

Methods: MS participants (n = 20; age = 45.4 ± 12.3 years, 7 males) underwent 3 T MRI scans before and after 20 daily sessions of dorsolateral prefrontal cortex (DLFPC) tDCS (2.0 mA, left anodal) paired with adaptive cognitive training (aCT). During both visits, imaging measurements of cerebral blood flow (CBF), cerebral venous blood oxygenation (Yv) and calculated cerebral metabolic rate of oxygen (CMRO2) were obtained at pre-tDCS, during-tDCS and post-tDCS.

Results: At baseline, significant increase from pre- to during-tDCS was observed in CMRO2 (7.6%; p = 0.002), CBF (11.0%; p < 0.0001) and Yv (1.9%; p = 0.006). At follow up, we observed an increase in pre-tDCS CMRO2 (140.59 ± 13.83 μmol/100 g/min) compared to baseline pre-tDCS levels (128.30 ± 14.00 μmol/100 g/min; p = 0.006). Sustained elevations in CMRO2 and CBF into post-tDCS were also observed (tDCS lingering effects). Cumulative tDCS effects were observed in the form of sustained elevations in CMRO2 and CBF in pre-tDCS follow up, reaching the magnitudes measured at baseline during-tDCS.

Discussion: TDCS induces an acute surge in metabolic activity persisting immediately after the stimulation is removed. Moreover, treatment composed of repeated tDCS-aCT paired sessions contributes to establishing long-lasting increases in neuronal activity.

New publication:

Frontal HD-tACS Enhances Behavioral and EEG Biomarkers of Vigilance in Continuous Attention Task

Nigel Gebodh, Vladimir Miskovic, Sarah Laszlo, Abhishek Datta, Marom Bikson

Brain Stimulation journal, 2024 DOI:https://doi.org/10.1016/j.brs.2024.05.009

The Bikson lab presents at the International Neuromodulation Society (INS), in Vancouver, Canada. May 11-15, 2024

1. “Do we need to understand mechanisms to invent the next breakthrough?” Marom Bikson, May 11 in the Innovation in Neuromodulation precon. Slides PDF

2. “Neurovascular Modulation: Is the Direct Stimulation of Brain Vasculature a Therapeutic Mechanism”, Marom Bikson, May 12, in the Noninvasive Brain Stimulaion) precon. Slides PDF.

3. “A New Disposable Electotherapy Platform”, Mohamad FallaRad, May 12, in the Noninvasive Brain Stimulaion) precon.

4. “Sub-Threshold Neuromodulation: Everything Old is New”. Marom Bikson, PLENARY, May 15. Slides PDF

New publication:

Front Neuroergon . 2024 Apr 10:5:1236486. doi: 10.3389/fnrgo.2024.1236486.

A pilot randomized controlled trial of transcranial direct current stimulation adjunct to moderate-intensity aerobic exercise in hypertensive individuals

Edson Silva-Filho 1 2, Marom Bikson 3, Nigel Gebodh 3, Niranjan Khadka 3, Amilton da Cruz Santos 1, Rodrigo Pegado 2, Maria do Socorro Brasileiro-Santos 1

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

2 Postgraduate Program in Physiotherapy and Postgraduate Program in Health Science, Federal University of Rio Grande do Norte, Santa Cruz, Brazil.

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

• PMID: 38660589 PMCID: PMC11040684

• DOI: 10.3389/fnrgo.2024.1236486

Marom Bikson lectues at NJIT on April 19. 2024 on “Design of non-invasive electrical brain stimulation”

Slides PDF

Marom Bikson speaks at the ANT Neuromeeting April 10-11, 2024 in Philadelphia, PA.

Dr. Bikson speaks on Biomarkers for Design. Slides PDF

2024 Bioelectronic Medicine Forum New York, April 5, 2024. website.

Location: Academy of Medicine, New York, NY (and Zoom)

Marom Bikson speaks on new models for neuromodulation distribution. Slides PDF.