Prof. Marom Bikson gives seminar to the Johns Hopkins University Translational Neuroengineering Technologies Network on “The Ins and Outs of tDCS”
Nov 24, 2020 (online)
Link to TNT program
Slides PDF
New publication Physics in Medicine & Biology
Role of skin tissue layers and ultra-structure in transcutaneous electrical stimulation including tDCS
Niranjan Khadka & Marom Bikson
Physics in Medicine & Biology | (2020) 65:22 | https://doi.org/10.1088/1361-6560/abb7c1
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Abstract: Background. During transcranial electrical stimulation (tES), including transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS), current density concentration around the electrode edges that is predicted by simplistic skin models does not match experimental observations of erythema, heating, or other adverse events. We hypothesized that enhancing models to include skin anatomical details, would alter predicted current patterns to align with experimental observations. Method. We develop a high-resolution multi-layer skin model (epidermis, dermis, and fat), with or without additional ultra-structures (hair follicles, sweat glands, and blood vessels). Current flow patterns across each layer and within ultra-structures were predicted using finite element methods considering a broad range of modeled tissue parameters including 78 combinations of skin layer conductivities (S m–1): epidermis (standard: 1.05 × 10−5; range: 1.05 × 10−6 to 0.465); dermis (standard: 0.23; range: 0.0023 to 23), fat (standard: 2 × 10−4; range: 0.02 to 2 × 10−5). The impact of each ultra-structures in isolation and combination was evaluated with varied basic geometries. An integrated final model is then developed. Results. Consistent with prior models, current flow through homogenous skin was annular (concentrated at the electrode edges). In multi-layer skin, reducing epidermis conductivity and/or increasing dermis conductivity decreased current near electrode edges, however no realistic tissue layer parameters produced non-annular current flow at both epidermis and dermis. Addition of just hair follicles, sweat glands, or blood vessels resulted in current peaks around each ultrastructure, irrespective of proximity to electrode edges. Addition of only sweat glands was the most effective approach in reducing overall current concentration near electrode edges. Representation of blood vessels resulted in a uniform current flow across the vascular network. Finally, we ran the first realistic model of current flow across the skin. Conclusion. We confirm prior models exhibiting current concentration near hair follicles or sweat glands, but also exhibit that an overall annular pattern of current flow remains for realistic tissue parameters. We model skin blood vessels for the first time and show that this robustly distributes current across the vascular network, consistent with experimental erythema patterns. Only a state-of-the-art precise model of skin current flow predicts lack of current concentration near electrode edges across all skin layers.
New Publication in Clinical Neurophysiology
Safety and recommendations for TMS use in healthy subjects and patient populations, with updates on training, ethical and regulatory issues: Expert Guidelines
Simone Rossi, Andrea Antal, Sven Bestmann, Marom Bikson, Carmen Brewer, Jürgen Brockmöller, Linda L. Carpenter, Massimo Cincotta, Robert Chen, Jeff D. Daskalakis, Vincenzo Di Lazzaro, Michael D. Fox, Mark S. George, Donald Gilbert, Vasilios K. Kimiskidis, Giacomo Koch, Risto J. Ilmoniemi, Jean Pascal Lefaucheur, Letizia Leocani, Sarah H. Lisanby, Carlo Miniussi, Frank Padberg, Alvaro Pascual-Leone, Walter Paulus, Angel V. Peterchev, Angelo Quartarone, Alexander Rotenberg, John Rothwell, Paolo M. Rossini, Emiliano Santarnecchi, Mouhsin M. Shafi, Hartwig R. Siebner, Yoshikatzu Ugawa, Eric M. Wassermann, Abraham Zangen, Ulf Ziemann, & Mark Hallett
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Abstract: This article is based on a consensus conference, promoted and supported by the International Federation of Clinical Neurophysiology (IFCN), which took place in Siena (Italy) in October 2018. The meeting intended to update the ten-year-old safety guidelines for the application of transcranial magnetic stimulation (TMS) in research and clinical settings (Rossi et al., 2009). Therefore, only emerging and new issues are covered in detail, leaving still valid the 2009 recommendations regarding the description of conventional or patterned TMS protocols, the screening of subjects/patients, the need of neurophysiological monitoring for new protocols, the utilization of reference thresholds of stimulation, the managing of seizures and the list of minor side effects.
New issues discussed in detail from the meeting up to April 2020 are safety issues of recently developed stimulation devices and pulse configurations; duties and responsibility of device makers; novel scenarios of TMS applications such as in the neuroimaging context or imaging-guided and robot-guided TMS; TMS interleaved with transcranial electrical stimulation; safety during paired associative stimulation interventions; and risks of using TMS to induce therapeutic seizures (magnetic seizure therapy).
An update on the possible induction of seizures, theoretically the most serious risk of TMS, is provided. It has become apparent that such a risk is low, even in patients taking drugs acting on the central nervous system, at least with the use of traditional stimulation parameters and focal coils for which large data sets are available. Finally, new operational guidelines are provided for safety in planning future trials based on traditional and patterned TMS protocols, as well as a summary of the minimal training requirements for operators, and a note on ethics of neuroenhancement.
2020 Neurotech Leaders Forum, November 16-17, 2020
Embassy Suites, San Francisco Airport Waterfront and Online, Program details
Dr. Marom Bikson to join panel on “Repelling the Invasion: Surface Stimulation Makes a Comeback” to speak on “Non-invasive Neuromodulation. Going home (in the time of COVID).”
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New publication in Brain Stimulation
Temporal interference stimulation targets deep brain regions by modulating neural oscillations
Zeinab Esmaeilpour, Greg Kronberg, Davide Reato, Lucas C. Parra, & Marom Bikson
Brain Stimulation | (2020) 11(7) | https://doi.org/10.1016/j.brs.2020.11.007
Abstract:
Background
Temporal interference (TI) stimulation of the brain generates amplitude-modulated electric fields oscillating in the kHz range with the goal of non-invasive targeted deep brain stimulation. Yet, the current intensities required in human (sensitivity) to modulate deep brain activity and if superficial brain region are spared (selectivity) at these intensities remains unclear.
Objective
We developed an experimentally constrained theory for TI sensitivity to kHz electric field given the attenuation by membrane low-pass filtering property, and for TI selectivity to deep structures given the distribution of modulated and unmodulated electric fields in brain.
Methods
The electric field threshold to modulate carbachol-induced gamma oscillations in rat hippocampal slices was determined for unmodulated 0.05-2 kHz sine waveforms, and 5 Hz amplitude-modulated waveforms with 0.1-2 kHz carrier frequencies. The neuronal effects are replicated with a computational network model to explore the underlying mechanisms, and then coupled to a validated current-flow model of the human head.
Results
Amplitude-modulated electric fields are stronger in deep brain regions, while unmodulated electric fields are maximal at the cortical regions. Both experiment and model confirmed the hypothesis that spatial selectivity of temporal interference stimulation depends on the phasic modulation of neural oscillations only in deep brain regions. Adaptation mechanism (e.g. GABAb) enhanced sensitivity to amplitude modulated waveform in contrast to unmodulated kHz and produced selectivity in modulating gamma oscillation (i.e. Higher gamma modulation in amplitude modulated vs unmodulated kHz stimulation). Selection of carrier frequency strongly affected sensitivity to amplitude modulation stimulation. Amplitude modulated stimulation with 100 Hz carrier frequency required ∼5 V/m (corresponding to ∼13 mA at the scalp surface), whereas, 1 kHz carrier frequency ∼60 V/m (∼160 mA) and 2 kHz carrier frequency ∼80 V/m (∼220 mA) to significantly modulate gamma oscillation. Sensitivity is increased (scalp current required decreased) for theoretical neuronal membranes with faster time constants.
Conclusion
The TI sensitivity (current required at the scalp) depends on the neuronal membrane time-constant (e.g. axons) approaching the kHz carrier frequency. TI selectivity is governed by network adaption (e.g. GABAb) that is faster than the amplitude-modulation frequency. Thus, we show neuronal and network oscillations time-constants determine the scalp current required and the selectivity achievable with TI in humans.
New publication in Brain Stimulation
Comparison of cortical network effects of high-definition and conventional tDCS during visuomotor processing
Pejman Sehatpour, Clément Dondé, Devin Adair, Johanna Kreither, Javier Lopez-Calderon, Michael Avissar, Marom Bikson, & Daniel C. Javitt
Brain Stimulation | (2021) 14(1):33-35 | https://doi.org/10.1016/j.brs.2020.11.004
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Work from the Bikson lat at the conference includes new models of ECT using “adaptive” methods.
(Updated) The CCNY Neural Engineering Group will have multiple presentations at the upcoming 7th International Conference on Non-invasive Brain Stimulation:
Tuesday, November 10th, 2020:
17:45-18:45 CET (UTC+1) | Zoom-Webinar 1: Workshop: NIBS teaching course – Modelling of TMS and TES induced electrical fields in the brain | Marom Bikson, Slides PDF Watch Bikson portion here
14:00 CET (UTC+1) | ePoster NIBS | Station 2: Effect of Electrode Preparation on Static Impedance in Electroconvulsive Therapy | Samantha Cohen et al. PDF. Video presentation available here.
14:00-16:00 CET (UTC+1) | ePoster NIBS | Station 10: Dynamic Models of Electroconvulsive Therapy: Implications for Programming, Electrodes, and Current Flow | Gozde Unal | Jaiti Swami et al. Poster PDF Read the paper preprint here
14:00-16:00 CET (UTC+1) | ePoster NIBS | Station 1: A new look, with old data, at the correlation between the static and dynamic impedance during electroconvulsive therapy (ECT) | Carliza Canela et al. PDF. Video presentation available here.
16:00 CET (UTC+1) | ePoster DGKN | Station 2: Mechanisms of Temporal Interference (TI) stimulation | Zeinab Esmaeilpour et al. Poster PDF . And read the paper here in Brain Stimulation journal. Video presentation available here.
Wednesday, November 11th, 2020:
14:00-14:45 CET (UTC+1) | NIBS PLENARY Livestream 1: Shared mechanisms of tDCS, tACS, Temporal Interference Stimulation, and ECT | Marom Bikson, download slides PDF Watch video here
17:30–18:00 CET (UTC+1) | Livestream 4: High-resolution modeling and large-animal validation of transcutaneous direct current stimulation of neurorehabilitation | Marom Bikson, Download slides PDF Watch video here
New publication in Clinical Psychology and Special Education
Case Series of tDCS as an Augmentation Strategy for Attention Bias Modification Treatment in Adolescents with Anxiety
Daniella Vaclavik, Michele Bechor, Adriana Foster, Leonard M. Gralnik, Yair Bar-Haim, Daniel S. Pine, Marom Bikson, Wendy K. Silverman, Bethany C. Reeb-Sutherland, & Jeremy W. Pettit
Clinical Psychology and Special Education | (2020) 9:3 | https://doi.org/10.17759/cpse.2020090308
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Abstract: This article presents the results of a case series to assess the feasibility, acceptability, and clinical promise of transcranial Direct Current Stimulation (tDCS) as an augmentation strategy in clinic referred adolescents. Attention Bias Modification Treatment (ABMT) is a computer-based attention-training protocol designed to reduce rapidly deployed attention orienting to threat and thereby reduce anxiety symptom severity. Studies of ABMT reveal overall small to medium effect sizes. Advances in the neural underpinnings of attention to threat and attention-training protocols suggest the potential of tDCS of the dorsolateral prefrontal cortex (dlPFC) as a novel augmentation strategy to enhance ABMT’s efficacy (ABMT + tDCS). However, tDCS has never been tested in a sample of adolescents with anxiety disorders. Six adolescents with a primary anxiety disorder completed all four ABMT + tDCS sessions. Adverse effects were mild and transient. Adolescents and parents independently reported fair to excellent levels of satisfaction. Impairment ratings of the primary anxiety disorder significantly decreased. Further, electrophysiological data recorded via electroencephalography (EEG) suggested decreases in neural resources allocated to threat. These findings support the feasibility, acceptability, and clinical promise of tDCS as an augmentation strategy in adolescents with anxiety disorders, and provide the impetus for further investigation using randomized controlled designs in larger samples.
New publication in Nature Scientific Reports
Modulation of solute diffusivity in brain tissue as a novel mechanism of transcranial direct current stimulation (tDCS)
Yifan Xia, Wasem Khalid, Zhaokai Yin, Guangyao Huang, Marom Bikson & Bingmei M. Fu
Scientific Reports | (2020) 10:18488 | https://doi.org/10.1038/s41598-020-75460-4
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Abstract: The breadth of brain disorders and functions reported responsive to transcranial direct current stimulation (tDCS) suggests a generalizable mechanism of action. Prior efforts characterized its cellular targets including neuron, glia and endothelial cells. We propose tDCS also modulates the substance transport in brain tissue. High resolution multiphoton microscopy imaged the spread across rat brain tissue of fluorescently-labeled solutes injected through the carotid artery after tDCS. The effective solute diffusion coefficient of brain tissue (Deff) was determined from the spatio-temporal solute concentration profiles using an unsteady diffusion transport model. 5–10 min post 20 min–1 mA tDCS, Deff increased by ~ 10% for a small solute, sodium fluorescein, and ~ 120% for larger solutes, BSA and Dex-70k. All increases in Deff returned to the control level 25–30 min post tDCS. A mathematical model for Deff in the extracelluar space (ECS) further predicts that this dose of tDCS increases Deffby transiently enhancing the brain ECS gap spacing by ~ 1.5-fold and accordingly reducing the extracellular matrix density. The cascades leading ECS modulation and its impact on excitability, synaptic function, plasticity, and brain clearance require further study. Modulation of solute diffusivity and ECS could explain diverse outcomes of tDCS and suggest novel therapeutic strategies.
Neuroergonomics is motivated to effectively apply neuroscientific methods and theories to understand how the brain works in everyday life. About this Event In the #1 installment of the Neuroergonomics Conference webinar series, we are pleased to host the launch of a new journal, Frontiers in Neuroergonomics. We invite the field editors and section editors of this new journal to share with us the opportunities for communicating your research.
Event is sold out but will stream Oct 27, 2020 at 10:30 am at this link
Besides this, we have the honor of hosting Prof. Art Kramer who will give a keynote lecture on “Implications of Physical Activity and Exercise on Cognitive and Brain Health.”.
This will be a great opportunity to meet like-minded colleagues and to find out ways to contribute to our rapidly growing community. See you there!!! Disclaimer: The Neuroergonomics Conference is a non-profit community-led initiative, independent from Frontiers Media S.A.
Program (Eastern Standard Time) 10:30 am -- Meet & Greet You, You, You and You Small breakout rooms to get to make new friends and catch up with old ones.
11:00 am -- Welcome remarks Field Chief Editors of the Frontiers Journal of Neuroergonomics Hasan Ayaz, Waldemar Karwowski, Frederic Dehais
11:15 am -- Panel Discussion "The many facets of Neuroergonomics" Specialty Chief Editors of the Frontiers Journal of Neuroergonomics Marom Bikson, Anne-Marie Brouwer, Daniel Callan, Stephen Fairclough, Klaus Gramann, Frank Krueger, Fabien Lotte, Stephene Perrey
11:45 am -- Keynote Talk "Implications of Physical Activity and Exercise on Cognitive and Brain Health" Art Kramer, Center for Cognitive and Brain Health, Northeastern University, US
Dr. Dennis Q. Truong, Dr. Niranjan Khadka, and Dr. Marom Bikson publish a chapter "Transcranial Electrical Stimulation" in the textbook Neural Engineering, edited by Bin He, published by Springer.
Download the chapter PDF
Chapter abstract: Transcranial electrical stimulation (tES) includes a range of devices where electric current is applied to electrodes on the head to modulate brain function. Various tES devices are applied to indications spanning neurological and psychiatric disorders, neuro-rehabilitation after injury, and altering cognition in healthy adults. All tES devices share certain common features including a waveform generator (typically current controlled), disposable electrodes or electrolyte, and an adhesive or headgear to position the electrodes. tES “dose” is defined by the size and position of electrodes and the waveform (current pattern, duration, and intensity). Many subclasses of tES are named based on dose. This chapter is largely focused on low-intensity (few mA) tES. Low-intensity tES includes transcranial direct-current stimulation (tDCS), transcranial alternating- current stimulation (tACS), and transcranial pulsed-current stimulation (tPCS). Electrode design is important for reproducibility, tolerability, and influences when and what dose can be applied. Stimulation impedance measurements monitor contact quality, while current control is typically used to ensure consistent current delivery despite electrode impedance unknowns. Computational current flow models support device design and programming by informing dose selection for a given outcome. Consensus on the safety and tolerability of tES is protocol-specific, but medical-grade tES devices minimize risk.
Keywords Transcranial · Electrical · Stimulation · tES · tDCS · tACS · tPCS · Neuromodulation · Electrode design · Noninvasive · Medical devices
Full book information
Application of Noninvasive Vagal Nerve Stimulation to Stress-Related Psychiatric Disorders
PMID: 32916852 DOI: 10.3390/jpm10030119 PDF
James Douglas Bremner, Nil Z Gurel, Matthew T Wittbrodt, Mobashir H Shandhi, Mark H Rapaport, Jonathon A Nye, Bradley D Pearce, Viola Vaccarino, Amit J Shah, Jeanie Park, Marom Bikson, Omer T Inan
Abstract
Background: Vagal Nerve Stimulation (VNS) has been shown to be efficacious for the treatment of depression, but to date, VNS devices have required surgical implantation, which has limited widespread implementation. Methods: New noninvasive VNS (nVNS) devices have been developed which allow external stimulation of the vagus nerve, and their effects on physiology in patients with stress-related psychiatric disorders can be measured with brain imaging, blood biomarkers, and wearable sensing devices. Advantages in terms of cost and convenience may lead to more widespread implementation in psychiatry, as well as facilitate research of the physiology of the vagus nerve in humans. nVNS has effects on autonomic tone, cardiovascular function, inflammatory responses, and central brain areas involved in modulation of emotion, all of which make it particularly applicable to patients with stress-related psychiatric disorders, including posttraumatic stress disorder (PTSD) and depression, since dysregulation of these circuits and systems underlies the symptomatology of these disorders. Results: This paper reviewed the physiology of the vagus nerve and its relevance to modulating the stress response in the context of application of nVNS to stress-related psychiatric disorders. Conclusions: nVNS has a favorable effect on stress physiology that is measurable using brain imaging, blood biomarkers of inflammation, and wearable sensing devices, and shows promise in the prevention and treatment of stress-related psychiatric disorders.
Prof. Marom Bikson to give the NIH keynote at the Academy of Aphasia 58th Annual Meeting 18-20 October, 2020 (online)
Title: transcranial Direct Current Stimulation (tDCS) boosts capacity for plasticity
Transcranial Direct Current Stimulation (tDCS) applies low-intensity current across the scalp in order to modulate brain function including to enhance neurorehabilitation. This talk explains the basics of tDCS technology, how tDCS can be customized to patients with brain injury, and how tDCS boosts the capacity for brain plasticity.
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Meeting website
Meeting information:
General keynote speaker is Dr. Elissa Newport of Georgetown University. Dr. Newport is a Professor of Neurology and Rehabilitation Medicine at the Georgetown University Medical Center, where she directs the Center for Brain Plasticity and Recovery. Dr. Newport runs the Learning and Development Lab, which studies the acquisition of language, the relationship between language acquisition and language structure, and the Pediatric Stroke Research Project, which studies the recovery of language after damage to the brain early in life.She has been recognized by a number of organizations for the impact of her theoretical and empirical contributions to the field of language acquisition. She has been elected as a fellow in the Association for Psychological Science, the Society of Experimental Psychologists, the Cognitive Science Society, the American Association for the Advancement of Science, the American Academy of Arts and Sciences, and the National Academy of Sciences. Her research has been supported by grants from the National Institutes of Health, the National Science Foundation, the McDonnell Foundation, and the Packard Foundation. In 2015 she received the Benjamin Franklin Medal in Computer and Cognitive Science.
Now in its third year, the NIDCD-funded Academy of Aphasia conference grant (R13 DC017375-01) will sponsor student fellows for focused mentoring and training, and includes a of state-of-the-art New Frontiers in Aphasia Research seminar. This year's topic will focus on transcranial direct current stimulation, and the NIH keynote speaker will be Dr. Marom Bikson of The City College of New York. Dr. Bikson is the Shames Professor in the Department of Biomedical Engineering where he directs the Neural Engineering Group. His work studies the effects of electricity on the human body and applies this knowledge toward the development of medical devices and electrical safety guidelines, including transcranial direct current stimulation. Both U.S. and international students are eligible to apply. Please contact Swathi Kiran (kirans@bu.edu) with inquiries.
The journal Neuromodulation: Technology at the Neural Interface publishes abstracts from the 2019 joint meeting of Neuromodulation: The Science and NYC Neuromodulation.
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The meeting was co-chaired by Marom Bikson, Roy Hamilton, Elliot Krames, and Eric Grigsby and help in Napa, California Oct 4-9, 2019 meeting website
The National Institutes of Health NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES awarded “BRIDGES TO THE BACCALAUREATE RESEARCH TRAINING PROGRAM AT LAGUARDIA COMMUNITY COLLEGE” to a team including LAGUARDIA COMMUNITY COLLEGE (PI Hendrick Delcham) and THE CITY COLLEGE OF NEW YORK (M-PI Marom Bikson).
LaGuardia Community College’s “Bridges to the Baccalaureate Program” provides mentored research (including at The City College of New York) experiences year round to qualified minority, economically disadvantaged or disabled students. Beyond the research experience, the program features instructional workshops on quantitative literacy (Biostatistics), oral presentation, research paper critiques, bio- instrumentations, research design, data science, mentoring, leadership and management skills, monthly research student seminars, tutoring, transfer and transfer counseling, student presentations at local and national conferences.
LaGuardia Community College’s “Bridges to the Baccalaureate Research Training Program” has demonstrated high graduation and high transfer rates for our students, conclusively demonstrating that a community college can take the lead in administering a successful Bridges program. Our program has formed a consortium LaGuardia Community College’s and three exceptional four-year colleges—the City College of New York, Hunter College, and Queens College—to provide challenging research experiences in the biomedical and behavioral sciences for our underrepresented college students: women, minorities, the disabled, and those from economically disadvantaged backgrounds. LaGuardia proposes to place 10 students in hands-on, mentored research experiences each year of the grant period. These students will choose from a list of research projects and will be engaged in preliminary, preparatory research at LaGuardia, under the tutelage of the LaGuardia Faculty Research Mentors. This experience gained will then be utilized during the summer, as the Bridges students become involved in more intensive research at our three linking colleges, Brookhaven National Laboratories, and SUNY downstate Medical Center. The Bridges program also features a number of activities designed to support the students: monthly research student seminars, tutoring, transfer counseling, opportunities to present their research results at local and national conferences, instruction in the Responsible Conduct of Research, Rigor and Reproducibility, instructional workshops on bio-statistics, leadership and self-management skills, bioinstrumentation, research paper critique, library research, research design, data science, introduction to Python, and poster presentation and the use of ePortfolios. The ePortfolio will be used by Bridges students to collect their academic work, progress report and to reflect on their learning and career goals. The program will also offer LaGuardia faculty the opportunity to participate in effective mentoring workshop offered at the university of Wisconsin and Bridges students will also enroll in the National Research Mentoring Network (NRMN). The monthly research seminars are notable in that they feature progress reports and formal final reports by the students themselves, presentations by CUNY faculty and outside speakers, information from the program’s transfer counselor, a session on developing and delivering professional presentations, and an Alumni Homecoming Day where Bridges alumni return to share their successes and research with current Bridges students. Bridges students will also use an adapted version of myIDP (Individual Development Plan) to explore careers in biomedical, sciences, and bioengineering.
Design and Rationale of the PACt-MD Randomized Clinical Trial: Prevention of Alzheimer's dementia with Cognitive remediation plus transcranial direct current stimulation in Mild cognitive impairment and Depression
Rajji TK, Bowie CR, Herrmann N, Pollock BG, Bikson M, Blumberger DM, Butters MA, Daskalakis ZJ, Fischer CE, Flint AJ, Golas AC, Graff-Guerrero A, Kumar S, Lourenco L, Mah L, Ovaysikia S, Thorpe KE, Voineskos AN, Mulsant BH; PACt-MD Study Group. .
J Alzheimers Dis . 2020;76(2):733-751. doi: 10.3233/JAD-200141. PDF
Evidence-based guidelines and secondary meta-analysis for the use of transcranial direct current stimulation (tDCS) in neurological and psychiatric disorders.
Fregni F, El-Hagrassy MM, Pacheco-Barrios K, Carvalho S, Leite J, Simis M, Brunelin J, Nakamura-Palacios EM, Marangolo P, Venkatasubramanian G, San-Juan S, Caumo W, Bikson M, Brunoni AR, Neuromodulation Center Working Group.
Int J Neuropsychopharmacol . 2020 Jul 26;pyaa051. doi: 10.1093/ijnp/pyaa051.
In press PDF
Niranjan Khadka, Marom Bikson. Neurovascular-modulation. bioRxiv 13046435 2020. DOI: https://doi.org/10.1101/2020.07.21.214494
Download PDF published in bioRxiv — DOI
Abstract
Neurovascular-modulation is based on two principles that derive directly from brain vascular ultra-structure, namely an exceptionally dense capillary bed (BBB length density: 972 mm/mm3) and a blood-brain-barrier (BBB) resistivity (ρ ~ 1x105 Ω.m) much higher than brain parenchyma/interstitial space (ρ ~ 4 Ω.m) or blood (ρ ~ 1 Ω.m).Principle 1: Electrical current crosses between the brain parenchyma (interstitial space) and vasculature, producing BBB electric fields (EBBB) that are > 400x of the parenchyma electric field (ĒBRAIN), which in turn modulates transport across the BBB. Specifically, for a BBB space constant (λBBB) and wall thickness (dth-BBB): analytical solution for maximum BBB electric field (EABBB) is given as:(ĒBRAIN x λBBB) / dth-BBB. Direct vascular stimulation suggests novel therapeutic strategies such as boosting metabolic capacity or interstitial fluid clearance. Boosting metabolic capacity impacts all forms of neuromodulation, including those applying intensive stimulation or driving neuroplasticity. Boosting interstitial fluid clearance has broad implications as a treatment for neurodegenerative disease including Alzheimer's disease.Principle 2: Electrical current in the brain parenchyma is distorted around brain vasculature, amplifying neuronal polarization. Specifically, vascular ultra-structure produces ~50% modulation of the average ĒBRAIN over the ~40 μm inter-capillary distance. The divergence of EBRAIN (activating function) is thus ~100 kV/m2 per unit average ĒBRAIN. This impacts all forms of neuromodulation, including Deep Brain Stimulation (DBS), Spinal Cord Stimulation (SCS), Transcranial Magnetic Stimulation (TMS), Electroconvulsive Therapy (ECT), and transcranial electrical stimulation (tES) techniques such a transcranial Direct Current Stimulation (tDCS). Specifically, whereas spatial profile of EBRAIN along neurons is traditionally assumed to depend on macroscopic anatomy, it instead depends on local vascular ultra-structure.
Callesen H, Habelt B, Wieske F, Jackson M, Khadka N, Mattei D, Bernhardt N, Heinz A, Liebetanz D, Bikson M, Padberg F, Hadar R, Nitsche MA, Winter C
Download: PDF published in Nature Translational Psychiatry – DOI
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Abstract
Involuntary movements as seen in repetitive disorders such as Tourette Syndrome (TS) results from cortical hyperexcitability that arise due to striato-thalamo-cortical circuit (STC) imbalance. Transcranial direct current stimulation (tDCS) is a stimulation procedure that changes cortical excitability, yet its relevance in repetitive disorders such as TS remains largely unexplored. Here, we employed the dopamine transporter-overexpressing (DAT-tg) rat model to investigate behavioral and neurobiological effects of frontal tDCS. The outcome of tDCS was pathology dependent, as anodal tDCS decreased repetitive behavior in the DAT-tg rats yet increased it in wild-type (wt) rats. Extensive deep brain stimulation (DBS) application and computational modeling assigned the response in DAT-tg rats to the sensorimotor pathway. Neurobiological assessment revealed cortical activity changes and increase in striatal inhibitory properties in the DAT-tg rats. Our findings show that tDCS reduces repetitive behavior in the DAT-tg rat through modulation of the sensorimotor STC circuit. This sets the stage for further investigating the usage of tDCS in repetitive disorders such as TS.
