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

August 28, 2020 at 12:00 PM ET, Prof. Marom Bikson speaks on

“Translating Non-Invasive Brain Stimulation Inventions: Academic and Industry Partnerships” at the 2020 Mid-scale Research Infrastructure (MSRI) conference hosted at the UCSD.

Slides: PDF

Complete program and free registration here

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

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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

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Download: PDF published in Nature Translational Psychiatry – DOI

Download Supplementary figures

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.

Dr. Marom Bikson to speak at OHBM 2020 on “fMRI (and EEG) and Head Modeling: Addressing State and Trait Predictors in Response to tES”

You can watch the a version of Dr. Bikson prerecorded talk here

Download the slides here

The Realistic Anatomically Detailed Open-source Spinal Cord Stimulation Model (RADO-SCS) is the most anatomically detailed and open-source spinal cord model for simulating all forms of Spinal Cord Stimulation (SCS), DRG stimulation, other forms of spinal cord modulation such as transpinal Direct Current Stimulation (tsDCS), and other forms of spinal modeling such as biomechanical. RADO-SCS is an open source spinal cord stimulation model designed in Solidworks 2016. Model includes detailed structures of the lower thoracic vertebrae (T10-T12) and the spinal column with an emphasis on spinal tissues, nerves, and vasculature. Layers of meninges protecting the gray and white matter such as epidural space, subdural space, arachnoid matter, CSF, and pia matter are designed in detail. Lissauer’s tract and rootlets carrying nerve fibers away from the spinal cord are also included in anatomical detail. STL and Solidworks files for this open source model, as well as any questions on use, can be requested at https://www.neuralengr.org/spinal-cor...

This work has been conducted in collaboration between Dr. Marom Bikson's and Scott Lempka’s research groups. This model of this video was published as and can be cited as: Khadka, N., Liu, X., Zander, H., Swami, J., Rogers, E., Lempka, S., Bikson, M., 2020. Realistic anatomically detailed open-source spinal cord stimulation (RADO-SCS) model. J. Neural Eng. https://doi.org/10.1088/1741-2552/ab8344

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This talk given at BioKorea 2020 explains "High-Definition Transcranial Direct Current Stimulation (HD-tDCS) : Low-power, Targeted, Non-invasive Electroceuticals for CNS diseases".

HD-tDCS is special among neuromodulation approaches in that it 1) can be delivered with a battery powered device, 2) it is non-invasive and very well tolerated, can be fully wearable, 3) can be targeted to anatomical regions including using individual MRI or EEG, 4) and can be functionally targeted since it is sub-threshold. No other brain stimulation technique combines all these features, and this talk explains each one in turn.

Watch the talk here

Download the talk PDF

All references (and more) can be found on the lab publication page here

$3 million NIH grant boosts CCNY minority PhD output

In a massive boost to its development of minority PhD students in biomedical disciplines, The City College of New York is the recipient of a new five-year $2,966,693 training grant from the National Institutes of Health (NIH).   Prof. Marom Bikson and Prof. Lucas Parra are among 30 participating faculty,

Full press release here

A prospective trial of intraoperative tissue oxygenation measurement and its association with anastomotic leak rate after Ivor Lewis esophagectomy. J Thorac Dis 2020;12(4):1449-1459

Adusumilli PS, Bikson M, Rizk NP, Rusch VW, Hristov B, Grosser R, Tan KS, ISarkaria IS, Huang J, Molena D, Jones DR, Bains MS.

http://dx.doi.org/10.21037/jtd.2020.02.58

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Brainbox Initiative Webinar: The Targeting Limits of Transcranial Electrical Stimulation. Marom Bikson of the The City College of New York

Hear the talk here

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Some additional Q&A posted here

This free, interactive session will equip delegates with a knowledge of: Modes of transcranial electrical stimulation including conventional tDCS and High-Definition tDCS. Insights on the mechanisms of tDCS that integrate results from advanced current flow and animal models. Using EEG to guide stimulation (reciprocity). New concepts in non-invasive sub-gyri targeting. Functional targeting and Hebbian neuromodulation. The uses and pitfalls of Anode/Cathode based intervention design. Automated tools for individuated modeling. Biophysical insights into Temporal interference stimulation. This webinar will take place at 14:00 BST on May 18, 2020 and will last for approximately 1 hour with time for questions.

New publication:

Guidelines for TMS/tES Clinical Services and Research through the COVID-19 Pandemic

Read it : online

Bikson M, Hanlon CH, Woods AJ, Gillick BT, Charvet L, Lamm C, Madeo G, Holczer A, Almeida J, Antal A, Ay MR, Baeken C, Blumberger DM, Campanella S, Camprodon J, Christiansen L, Colleen L, Crinion J, Fitzgerald P, Gallimberti L, Ghobadi-Azbari P, Ghodratitoostani I, Grabner R, Hartwigsen G, Hirata A, Kirton A, Knotkova H, Krupitsky E, Marangolo M, Nakamura-Palacios EM, Potok W, Praharaj SK, Ruff CC, Schlaug G, Siebner HR, Stagg CJ, Thielscher A, Wenderoth N, Yuan T, Zhang X, Ekhtiari H. . 2020

Dr. Marom Bikson leads with Dr. Hamed Ekhtiari and international team on experts.

• We developed a framework for balancing the importance of NIBS operations with safety considerations, which facilitates the re-establishment of access to NIBS clinical services and research operations during COVID-19.

• The present consensus paper provides guidelines and good practices for managing and reopening NIBS clinics and laboratories through the immediate and ongoing stages of COVID-19.

• The proposed robust and structured strategy aims to address the current and anticipated future challenges while maintaining scientific rigor and managing risk.

Published in Brain Stimulation:

Transcranial Electrical Stimulation Motor Threshold Can Estimate Individualized tDCS Dosage from Reverse-Calculation Electric-Field Modeling

Kevin A. Caulfield, Bashar W. Badran , William H. DeVries, Philipp M. Summers, Emma Kofmehl, Xingbao Li, Jeffrey J. Borckardt, Marom Bikso,n Mark S. George

Free online

• Reverse-calculation electric-field modeling can estimate individualized tDCS doses.

• Individualized tDCS doses widely vary (range: 3.75 to 9.74mA to produce 1V/m).

• •DCS applied at a uniform 1-2mA dose may underdose some individuals.

• Transcranial electrical stimulation (TES) motor thresholds (MTs) correlate with reverse-calculation tDCS doses (R2 = 0.45, p < 0.001).

• TES MT or reverse-calculation modeling could become methods to individually dose tDCS and warrant further investigation.

Prof. Marom Bikson among the scientists featured in Freethink article “Treating Depression at Home with a tDCS Headset”

Read it here

New publication: Brain Stimulation Journal VOLUME 13, ISSUE 3, P686-693, MAY 01, 2020

Supervised transcranial direct current stimulation (tDCS) at home: A guide for clinical research and practice Leigh E. Charvet. Michael T. Shaw, Marom Bikson, Adam J. Woods Helena Knotkova

PDF

Background: Transcranial direct current stimulation (tDCS) is a method of noninvasive neuromodulation and potential therapeutic tool to improve functioning and relieve symptoms across a range of central and peripheral nervous system conditions. Evidence suggests that the effects of tDCS are cumulative with consecutive daily applications needed to achieve clinically meaningful effects. Therefore, there is growing interest in delivering tDCS away from the clinic or research facility, usually at home. Objective: To provide a comprehensive guide to operationalize safe and responsible use of tDCS in home settings for both investigative and clinical use. Methods: Providing treatment at home can improve access and compliance by decreasing the burden of time and travel for patients and their caregivers, as well as to reach those in remote locations and/or living with more advanced disabilities. Results: To date, methodological approaches for at-home tDCS delivery have varied. After implementing the first basic guidelines for at-home tDCS in clinical trials, this work describes a comprehensive guide for facilitating safe and responsible use of tDCS in home settings enabling access for repeated administration over time. Conclusion: These guidelines provide a reference and standard for practice when employing the use of tDCS outside of the clinic setting.

Niranjan Khadka, Xijie Liu, Hans Zander, Jaiti Swami, Evan Rogers, Scott F Lempka, Marom Bikson. Realistic anatomically detailed open-source spinal cord stimulation (RADO-SCS) model. Journal of Neural Engineering 2020. DOI: 10.1088/1741-2552/ab8344

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Download PDF published in Journal of Neural Enginnering — DOI

Abstract

Objective:

Computational current flow models of spinal cord stimulation (SCS) are widely used in device development, clinical trial design, and patient programming. Proprietary models of varied sophistication have been developed. An open-source model with state-of-the-art precision would serve as a standard for SCS simulation.

Approach:

We developed a sophisticated SCS modeling platform, named Realistic Anatomically Detailed Open-Source Spinal Cord Stimulation (RADO-SCS) model. This platform consists of realistic and detailed spinal cord and ancillary tissues anatomy derived based on prior imaging and cadaveric studies. In our finite element model of the T9-T11 spine levels, we represented the following tissues: vertebrae, intervertebral disc, epidural space, epidural space vasculature, dura mater, dural sac, intraforaminal tissue, cerebrospinal fluid (CSF), whitematter, spinal cord vasculature, Lissauer’s tract, gray matter, dorsal and ventral roots and rootlets, dorsal root ganglion (DRG), sympathetic chain (trunk and ganglion), thoracic aorta and its branching, peripheral vasculature, and soft tissues (thorax). As an exemplary application to illustrate the model workflow, we simulated a bipolar SCS montage and calculated the corresponding activation thresholds for individual axons populating the spinal cord.

Main results:

RADO-SCS provides state-of-the-art precision across 19 tissue compartments. The resulting model calculations of the electric fields generated in the white-matter and gray matter, and the axonal activation thresholds are broadly consistent with prior simulations.

Significance:

The RADO-SCS can be used to simulate any SCS approach with both unprecedented resolution (precision) and transparency (reproducibility). Freely-available online, the RADO-SCS will be updated continuously with version control.