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

Ahlam Salameh , Jessica McCabe , Margaret Skelly , Kelsey Rose Duncan, Zhengyi Chen , Curtis Tatsuoka , Marom Bikson , Elizabeth C. Hardin , Janis J. Daly and Svetlana Pundik

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

Congratulations to Abbe Pannuci, featured as a 2022 CCNY Great Grad, graduating with Bachelor of Science Degree in Biotechnology! Abbe worked in our lab in the engineering of our SafeToddle Toddler Cane! Best of luck in your future studies as a Physician Assistant!

Abbe Pannuci, 2022 CCNY Great Grad

When Abbe Pannucci was 10 years old, she was diagnosed with Stage 4 cancer, a diagnosis that subjected her to two years of chemotherapy and radiation therapy. When she was 11 and a half, she earned her second-degree black belt in karate. At 12, she dedicated herself to the study of science “with the goal of contributing to research that helps minimize the severity of a cancer diagnosis for others.”

She credits the Macaulay Honors College for helping to launch her on that journey. After spending a summer interning at the U.S. Army Medical Research Institute of Infectious Diseases in Fort Detrick, Md., near her hometown, where she “got my hands on some real science,” she applied to City College. “I definitely knew I wanted to go to CCNY; it was just that I didn’t think I would get into the Macaulay Honors College when I applied” – but she did.

She has made the most of that decision, participating in clubs, acting as a peer mentor and orientation leader, and conducting research in the labs of Professor of Biomedical Engineering Marom Bikson and Dean of the Division of Science Susan Perkins, a biologist and her thesis advisor.

In addition to interning at Rockefeller University and Columbia University Medical Center, Pannucci volunteers as a patient advocate for Children’s National Medical Center in Washington, where she was treated, to help to improve the experience of current patients and to encourage new research in pediatric oncology.

Pannucci plans to spend the next year as an oncology laboratory technician before applying to the Physician’s Assistant Program at City College.

All of these experiences to date— and the ones yet to come—“help me give back to the community that helped me so much during my diagnosis,” she said.

Prof. Marom Bikson gives the keynote at the “Current Topics in Transcranial Electrical Stimulation Workshop” hosted by National Center of Neuromodulation for Rehabilitation at the Medical University of South Carolina. June 1 and 2, 2022.

Full program link Free in-person and Zoom,

Dr. Bikson will speak on June 1 , 2022 at 4 PM (ET) on “tES Technology: A difference to be a difference, must make a difference.” talk slides: PDF

( Additional talk materials: Program for the Third International Conference on Transcranial Magnetic and direct Current Stimulation held in Gottingen, Germany in 2008. And my slides from a talk at the conference in 2008).

Dr. Gozde Unal will also be speaking at the conference on June 2 on “Theoretical underpinnings of electrical field modelling.”

New paper in Brain Stimulation journal. “Efficacy and safety of HD-tDCS and respiratory rehabilitation for critically ill patients with COVID-19 The HD-RECOVERY randomized clinical trial”. DOI: https://doi.org/10.1016/j.brs.2022.05.006

RCT of Non-invasive Brain Stimulation+ respiratory rehabilitation in 56 critically ill COVID-19 patients. HD-tDCS markedly reduces time on ventilator & organ failure of COVID-19 patients with Acute Respiratory Distress Syndrome (ADRS).

Including customization of High-Definition transcranial Direct Current Stimulation (HD-tDCS) for COVID-19 ICU. HD-tDCS provided targeted non-invasive neuromodulation in a battery-powered portable form factor.

We’er proud of our Neural Engineering lab members recognized at the City College of New York, Biomedical Engineering Department (BME) 2022 awards ceremony . The day also included the BME Senior Design presentations.

Cynthia Poon & Carli Canela: Wallace Coulter Award Undergrad Research Excellence.

Gozde Unal: Wallace Coulter Graduate Student Research.

Zeinab Esmaeilpour: Harold Shames Graduate Student Award

Vividha Bhaskar: Undergrad academics excellence.

Gozde Unal, a PhD candidate in the lab of Dr. Marom Bikson will defend her dissertation thesis on Friday, May 13, 2022 at 11am. A copy of her abstract is below. If you would like to attend, please contact Gozde at gunal000@citymail.cuny.edu for the Zoom meeting ID. The meeting is also taking place in person in the Center for Discovery & Innovation 3rd floor conference room (CDI 3.352)

Abstract

Improvements in electroconvulsive therapy (ECT) outcomes have followed refinement in device electrical output and electrode montage. The physical properties of the ECT stimulus, together with those of the patient’s head, determine the impedances measured by the device and govern current delivery to the brain and ECT outcomes. However, the precise relations among physical properties of the stimulus, patient head anatomy, and patient-specific impedance to the passage of current are long-standing questions in ECT research and practice. In this thesis, we develop a computational framework based on diverse clinical data sets. We developed anatomical MRI-derived models of transcranial electrical stimulation (tES) that included changes in tissue conductivity due to local electrical current flow. These “adaptive” models simulate ECT both during therapeutic stimulation using high current and when dynamic impedance is measured, as well as prior to stimulation when low current is used to measure static impedance. We modeled two scalp layers: a superficial scalp layer with adaptive conductivity that increases with electric field up to a subject-specific maximum (σSS̅̅̅̅), and a deep scalp layer with a subject-specific fixed conductivity (σDS). We demonstrated that variation in these scalp parameters may explain clinical data on subject-specific static impedance and dynamic impedance, their imperfect correlation across subjects, their relationships to seizure threshold, and the role of head anatomy. Adaptive tES models demonstrated that current flow changes local tissue conductivity which in turn shapes current delivery to the brain in a manner not accounted for in fixed tissue conductivity models. Our predictions that variation in individual skin properties, rather than other aspects of anatomy, largely govern the relationship between static impedance, dynamic impedance, and ECT current delivery to the brain, themselves depend on assumptions about tissue properties. Broadly, our novel modeling pipeline opens the door to explore how adaptive-scalp conductivity may impact transcutaneous electrical stimulation (tES). Lastly, we incorporate the (device specific) role of frequency with a single overall assumption allowing quasi-static stimulations of ECT: appropriately parametrizing effective resistivity at single representative frequency (e.g., at 1 kHz), including subject-specific and adaptive skin resistivities. We only stipulate that our functions for (adaptive) resistivity at 1 kHz explain local tissue resistivity as they impact the static and dynamic impedance measures by specific ECT devices (e.g., Thymatron).

New CCNY Neural Engineering publication in Front Pain Res (Lausanne). 2022; 3: 798056.

PMCID: PMC8915734 PMID: 35295794 Full paper

The Concept, Development, and Application of a Home-Based High-Definition tDCS for Bilateral Motor Cortex Modulation in Migraine and Pain Alexandre F. DaSilva, Abhishek Datta, Jaiti Swami, Dajung J. Kim, Parag G. Patil, and Marom Bikson.

Abstract Whereas, many debilitating chronic pain disorders are dominantly bilateral (e.g., fibromyalgia, chronic migraine), non-invasive and invasive cortical neuromodulation therapies predominantly apply unilateral stimulation. The development of excitatory stimulation targeting bilateral primary motor (M1) cortices could potentially expand its therapeutic effect to more global pain relief. However, this is hampered by increased procedural and technical complexity. For example, repetitive transcranial magnetic stimulation (rTMS) and 4 × 1/2 × 2 high-definition transcranial direct current stimulation (4 × 1/2 × 2 HD-tDCS) are largely center-based, with unilateral-target focus—bilateral excitation would require two rTMS/4 × 1 HD-tDCS systems. We developed a system that allows for focal, non-invasive, self-applied, and simultaneous bilateral excitatory M1 stimulation, supporting long-term home-based treatment with a well-tolerated wearable battery-powered device. Here, we overviewed the most employed M1 neuromodulation methods, from invasive techniques to non-invasive TMS and tDCS. The evaluation extended from non-invasive diffuse asymmetric bilateral (M1-supraorbital [SO] tDCS), non-invasive and invasive unilateral focal (4 × 1/2 × 2 HD-tDCS, rTMS, MCS), to non-invasive and invasive bilateral bipolar (M1-M1 tDCS, MCS), before outlining our proposal for a neuromodulatory system with unique features. Computational models were applied to compare brain current flow for current laboratory-based unilateral M11 and bilateral M12 HD-tDCS models with a functional home-based M11−2 HD-tDCS prototype. We concluded the study by discussing the promising concept of bilateral excitatory M1 stimulation for more global pain relief, which is also non-invasive, focal, and home-based.

New lab publication from Bikson lab and Martin lab:

Williams PTJA, Truong DQ, Seifert AC, Xu K, Bikson M, Martin JH (2022) Selective augmentation of corticospinal motor drive with trans-spinal direct current stimulation in the cat. Brain Stimulation. DOI:https://doi.org/10.1016/j.brs.2022.03.007

Zeinab Esmaeilpour, a PhD candidate in the lab of Dr. Marom Bikson will defend her dissertation thesis on Monday, April 4, 2022 at 3pm. A copy of her abstract is below. If you would like to attend, please contact Zeinab at zesmaeilpour@ccny.cuny.edu for the Zoom meeting ID. The meeting is also taking place in person in the Center for Discovery & Innovation 3rd floor conference room (CDI 3.352)

Abstract

There is a tremendous interest in the use of non-invasive electrical stimulation for enhancing brain function in a healthy population as well as treating brain disorders in patients. Understanding the cellular mechanism of direct current (DC) and kilohertz (kHz) electrical stimulation is of broad interest in neuromodulation. More specifically, there is a large mismatch between enthusiasm for clinical applications of the method and understanding of DC and kHz novel mechanisms of action. This dissertation is centered around two main fundamental aims: 1) systematic study of the acute and long-term effects of kilohertz electrical stimulation and amplitude modulated waveform with kHz carrier frequency using a well-established animal model, hippocampal brain slice, 2) study the effect of tDCS on water exchange rate across the blood-brain barrier using an advanced MRI imaging technique in a healthy population to investigate effect of tDCS stimulation on Blood brain barrier.

The neuronal membrane has a well-established low pass filtering characteristic. This feature attenuates the sensitivity of the nervous system to any waveforms with high-frequency components. On the contrary, kilohertz stimulation has recently revolutionized spinal cord stimulation and even generated promising results in transcranial electrical stimulation. Investigating the effect of low kilohertz stimulation for neuromodulation is of huge interest. In this study we developed experimental designs to systematically investigate the frequency and dose-response of neuronal activity to unmodulated and amplitude modulated waveforms in low kilohertz range. The results support the theory of membrane attenuation of high-frequency stimulation. While supported by membrane characteristics of neurons, we uncovered that using low kilohertz stimulation diminishes the sensitivity of hippocampal neurons to electrical stimulation. Moreover, Amplitude-Modulated waveforms can generate a different pattern of modulation with even higher sensitivity to stimulation. However, the required electric field, in this case, is still significantly higher than low-frequency stimulation methods such as tACS.

Effects of DC stimulation have been studied in neuronal depolarization/hyperpolarization, synaptic plasticity, and neuronal network modulation. Recent evidence suggests that DC stimulation can induce polarity-dependent water exchange rate across the blood-brain barrier (BBB) in cell culture experiments through a mechanism called electroosmosis. Modulating the water exchange rate across BBB is of broad interest in neurological diseases such as dementia, Alzheimer’s, and stroke where the brain clearance system is disrupted. Investigating the effect of electrical stimulation on water exchange across BBB can potentially lead to complimentary treatment options. We used an advanced MRI technique to investigate induced changes in cerebral blood flow (CBF) and water exchange rate across BBB during stimulation in areas under electrodes. Contrary to our hypothesis, we could not detect changes in the water exchange rate across BBB.

In conclusion, in our efforts to investigate effects of high frequency stimulation we found that sensitivity of neuronal networks to oscillating electrical stimulation is governed by time constant of neuronal membrane. Moreover, neuronal networks are selective to different kilohertz waveforms (i.e., amplitude modulated) which is governed by nonlinear adaptive mechanisms in the network. For the effect of DC stimulation on neurovascular units, we hypothesized that stimulation affects water exchange rate across BBB through a mechanism known as electroosmosis which is a very small portion of a large water exchange across BBB through active transport. We believe that this may be the answer to our negative results in experiments.

TS. Baker, A.L. Zannou, D. Cruz, N. Khadka, C. Kellner, R. Tyc, M. Bikson, A. Costa.(2022) Development and Clinical Validation of a Finite Element Method Model Mapping Focal Intracranial Cooling. IEEE Transactions on Neural Systems and Rehabilitation Engineering, doi: 10.1109/TNSRE.2022.3161085.

Publication link

Abstract:

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

Niranjan Khadka, Marom Bikson. Noninvasive Electrical Brain Stimulation of the Central Nervous System. 2022. Handbook of Neuroengineering. Springer. https://doi.org/10.1007/978-981-15-2848-4_59-1

Download PDF | Weblink

Abstract

Noninvasive electrical brain stimulation of the central nervous system spans a broad range of devices and techniques that aim to change brain function with electrical current applied through electrodes on the surface of the body. The applications of such techniques span treatment of a wide range of neuropsychiatric disorders, healing of the nervous system after an injury, and experimental manipulations to study brain function. This chapter focuses on transcranial electrical stimulation (tES) which involves electrodes placed on the scalp with the goal of passing current through the skull and directly stimulate the cortex. tES itself is divided into subtechniques that are classified by the waveform applied and/or by the application of intended use. All tES devices share certain common features including a waveform generator and electrodes that are fully disposable or include a disposable component. The device applies the waveform to the electrodes through lead wires. tES “dose” is defined by the size and position of electrodes, and waveform includes the pattern, duration, and intensity of current. Versions of low-intensity tES include transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS). Impedance measurement is largely used to monitor acceptability of electrode-skin properties. Computational FEM models of current flow support device design and programming by informing how to select dose to produce a given outcome. The evidence for tES use across varied clinical applications, spanning treatment of neuropsychiatric disorders and neurorehabilitation following injury, as well as a tool to change cognition and behavior in healthy individuals is developing.

New lab publication:

Transcranial Electrical Stimulation for Psychiatric Disorders in Adults: A Primer

Hyein Cho, Ph.D., Lais B. Razza, B.A., Lucas Borrione, M.D., Marom Bikson, Ph.D., Leigh Charvet, Ph.D., Tracy A. Dennis-Tiwary, Ph.D., Andre R. Brunoni, M.D., Ph.D., Pedro Sudbrack-Oliveira, M.D.

Published Online:25 Jan 2022 https://doi.org/10.1176/appi.focus.20210020

Read the PDF

New lab publication:

Short-Term Efficacy of Transcranial Focused Ultrasound to the Hippocampus in Alzheimer’s Disease: A Preliminary Study journal link read PDF

by Hyeonseok Jeong 1,2, In-Uk Song 3, Yong-An Chung 1,2, Jong-Sik Park 3,Seung-Hee Na 3,Jooyeon Jamie Im 1, Marom Bikson 4, Wonhye Lee 5 and Seung-Schik Yoo 5

1 Department of Nuclear Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 21431, Korea

2 Department of Radiology, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 21431, Korea

3 Department of Neurology, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 21431, Korea

4 Department of Biomedical Engineering, The City College of New York, New York, NY 10031, USA

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

J. Pers. Med. 2022, 12(2), 250; https://doi.org/10.3390/jpm12020250

Abstract: Preclinical studies have suggested that low-intensity transcranial focused ultrasound (tFUS) may have therapeutic potential for Alzheimer’s disease (AD) by opening the blood–brain barrier (BBB), reducing amyloid pathology, and improving cognition. This study investigated the effects of tFUS on BBB opening, regional cerebral metabolic rate of glucose (rCMRglu), and cognitive function in AD patients. Eight patients with AD received image-guided tFUS to the right hippocampus immediately after intravenous injection of microbubble ultrasound contrast agents. Patients completed magnetic resonance imaging (MRI), 18F-fluoro-2-deoxyglucose positron emission tomography (PET), and cognitive assessments before and after the sonication. No evidence of transient BBB opening was found on T1 dynamic contrast-enhanced MRI. However, immediate recall (p = 0.03) and recognition memory (p = 0.02) were significantly improved on the verbal learning test. PET image analysis demonstrated increased rCMRglu in the right hippocampus (p = 0.001). In addition, increases of hippocampal rCMRglu were correlated with improvement in recognition memory (Spearman’s ρ = 0.77, p = 0.02). No adverse event was observed. Our results suggest that tFUS to the hippocampus of AD patients may improve rCMRglu of the target area and memory in the short term, even without BBB opening. Further larger sham-controlled trials with loger follow-up are warranted to evaluate the efficacy and safety of tFUS in patients with AD

New publication.:

E. Silva-Filho, G. Pilloni, L.E. Charvet, F. Fregni, A.R. Brunoni, M. Bikson. Factors supporting availability of home-based Neuromodulation using remote supervision in middle-income countries; Brazil experience. Brain Stimulation 2022 Letter-to-the-Editor link

Presented on on Jan 15th, 2022. Here are the slides

High density SCS increases spinal tissue temperature

Neurocapillary-modulation

Marom Bikson co-directs with Scott Lempka the”Engineering principles of DBS and SCS in clinical practice: General introduction and emerging concepts” pre-conference course on Jan 13, 2022

CCNY Neural Engineering is at the North American Neuromodulation Society (NANS) 2022 meerting:

Dr. Bikson also lectures at the Jan 13, 2022 pre-conference course on “Neurostimulation fundamentals: Dose, current flow, and neural activation.” Download slides

Jan 14, 2022 Dr. Bikson lectures on “Spinal Cord Stimulation (SCS): Subthreshold Mechanisms.” in the Engineering Principles in Neurostimulation: Emerging Concepts session 1/14/2022, 10:30 am - 12:00 pm Download slides

“Scientists want to treat Long Covid by zapping the brain with electricity”

THOM DUNN 6:15 AM TUE JAN 11, 2022. Read the article on BoingBoing here

And stay up to day on the science of neuromodulation for (long) Covid through Neuromodec here

“Zapping the Brain and Nerves Could Treat Long COVID Pilot studies test electrical treatments for the still-mysterious malady” by ELIZA STRICKLAND In IEEE Spectrum. Read the article here

The Bikson lab’s work with New York University (NYU) Langone, Federal University of Paraiba (Brazil), and Medical University of South Carolina were featured.

“Marom Bikson notes that both the research field and the industry of neurostimulation is just getting started. “We don’t have Pfizers of neuromodulation,” he says, “but you can only imagine what would happen if it shows an effect on long COVID.” It could lead to millions of people having stimulators in their homes, he suggests, which could open other doors. “Once you start stimulating for long COVID, you can start stimulating for other things like depression,” he says. But he says it’s crucial to proceed cautiously and not make unsupported claims for neurostimulation’s powers. “Otherwise,” he says, “it could have the opposite effect.”

Pictured are Edson Meneses, Gozde Unal, Nigel Gebodh, and Marom Bikson

Dr. Marom Bikson will speak at the American Association for the Advancement of Science (AAAS) annual meeting.

PDF of slides: download