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

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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

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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

Transcranial Electrical Stimulation (tES)

Niranjan Khadka, Marom Bikson

NeuroTechX (2021) |The NeuroTech Primer: A Beginner’s Guide to Everything Neurotechnology | ASIN: B09CKP1D66 | ISBN: 979-8454254056| Pp: 109-125 |

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Abstract:

Transcranial electrical stimulation (tES) devices apply electrical waveforms through electrodes placed on the scalp to modulate brain function. Various types of tES devices are used for a wide range of indications spanning neurological and psychiatric disorders, blood-brain barrier polarization, neurorehabilitation after injury, and altering cognition in healthy adults. All tES devices share certain common features including a waveform generator (typically a current controlled source), electrodes that are either fully disposable or include a disposable electrolyte, and an adhesive to position the electrodes on the scalp. Various tES subclasses are named based on dose. For example, Electroconvulsive therapy (ECT) is a special class of tES applying high stimulation intensity. tES “dose” is defined by the size and position of electrodes, and waveform including the pattern, duration, and intensity of the current.

The 4th International Brain Stimulation Conference on Dec 6-9. 2021 in Charleston. Conference info

The CCNY Neural Engineering lab will be making multiple presentations:

Talks

tDCS news: COVID-19 and PASC treatment, Neurovascular-modulation, and Games

Marom Bikson Slides PDF

Computational model of electroconvulsive therapy considering electric field dependent skin conductivity

Gozde Unal , Jaiti Swami, Carliza Canela, Samantha Cohen, Niranjan Khadka, Mohammad Rad1, Baron Short, Miklos Argyelan, Harold Sackeim, Marom Bikson

History and recent advancements and changes in computational modeling methods for transcranial electrical stimulation slides

Marom Bikson

Poster Presentations

A large open source neuromodulation dataset of concurrent EEG, ECG, behavior, and transcranial electrical stimulation

Nigel Gebodh, Zeinab Esmaeilpour, Abhishek Datta, Marom Bikson

P1.106 | Full Abstract >>

A novel approach to closed-loop neuromodulation with machine learning

Nigel Gebodh, Marom Bikson

P2.106 | Full Abstract >>

Neurocapillary-modulation

Niranjan Khadka, Marom Bikson

P3.006 | Full Abstract >>

Computational model of electroconvulsive therapy considering electric field dependent skin conductivity

Gozde Unal, Jaiti Swami, Carliza Canela,...Miklos Argyelan, Harold Sackeim, Marom Bikson

P3.102 | Full Abstract >>

Prof. Marom Bikson lectures at the online XIII International Symposium on Neuromodulation on Nov 21, 2022 on the topic of “Transcranial direct current stimulation changes brain vasculature (and Non-invasive neuromodulation in the post COVID-19 world)”.

Conference program (Nov 21-24, 2022)

Downloads slides PDF

New paper in Brain Stimulation

Weak DCS causes a relatively strong cumulative boost of synaptic plasticity with spaced learning

Mahim Sharma, Forouzan Farahani, Marom Bikson, & Lucas C. Parra

Brain Stimulation | (2021) 15(1):57–62 | https://doi.org/10.1016/j.brs.2021.10.552

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Abstract: Background: Electric fields generated during direct current stimulation (DCS) are known to modulate activity-dependent synaptic plasticity in-vitro. This provides a mechanistic explanation for the lasting behavioral effects observed with transcranial direct current stimulation (tDCS) in human learning experiments. However, previous in-vitro synaptic plasticity experiments show relatively small effects despite using strong fields compared to what is expected with conventional tDCS in humans (20 V/m vs. 1 V/m). There is therefore a need to improve the effectiveness of tDCS at realistic field intensities. Here we leverage the observation that effects of learning are known to accumulate over multiple bouts of learning, known as spaced learning.

Hypothesis: We propose that effects of DCS on synaptic long-term potentiation (LTP) accumulate over time in a spaced learning paradigm, thus revealing effects at more realistic field intensities.

Methods: We leverage a standard model for spaced learning by inducing LTP with repeated bouts of theta burst stimulation (TBS) in hippocampal slice preparations. We studied the cumulative effects of DCS paired with TBS at various intensities applied during the induction of LTP in the CA1 region of rat hippocampal slices. Results: As predicted, DCS applied during repeated bouts of theta burst stimulation (TBS) resulted in an increase of LTP. This spaced learning effect is saturated quickly with strong TBS protocols and stronger fields. In contrast, weaker TBS and the weakest electric fields of 2.5 V/m resulted in the strongest relative efficacies (12% boost in LTP per 1 V/m applied).

Conclusions: Weak DCS causes a relatively strong cumulative effect of spaced learning on synaptic plasticity. Saturation may have masked stronger effects sizes in previous in-vitro studies. Relative effect sizes of DCS are now closer in line with human tDCS experiments.

Title: Technology and science of of transcranial Direct Current Stimulation (tDCS) can boost brain function and capacity for plasticity

Abstract : Transcranial direct current stimulation (tDCS) is a non-invasive wearable technique where weak direct current is applied to the brain. This presentation explains the technological basics of tDCS and its understood mechanisms of action, along with how tDCS can be customized to diverse applications. Topics covered:

1) Basics of tDCS dosing including electrode placement, conventional and HD electrodes

3) Customizing electrode placement for subjects based on individual anatomical MRI or functional imaging

4) "Functional targeting" a mechanism to boost the efficacy of cognitive and behavioral therapies

5) A new concept of "neurovascular modulation", where tDCS direct activates vascular function blood flow and BBB transport

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New paper in Scientific Data

Dataset of concurrent EEG, ECG, and behavior with multiple doses of transcranial electrical stimulation

Nigel Gebodh, Zeinab Esmaeilpour, Abhishek Datta & Marom Bikson

Nature Scientific Data | (2021) 8, 274 | https://doi.org/10.1038/s41597-021-01046-y

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Abstract: We present a dataset combining human-participant high-density electroencephalography (EEG) with physiological and continuous behavioral metrics during transcranial electrical stimulation (tES). Data include within participant application of nine High-Definition tES (HD-tES) types, targeting three cortical regions (frontal, motor, parietal) with three stimulation waveforms (DC, 5 Hz, 30 Hz); more than 783 total stimulation trials over 62 sessions with EEG, physiological (ECG, EOG), and continuous behavioral vigilance/alertness metrics. Experiment 1 and 2 consisted of participants performing a continuous vigilance/alertness task over three 70-minute and two 70.5-minute sessions, respectively. Demographic data were collected, as well as self-reported wellness questionnaires before and after each session. Participants received all 9 stimulation types in Experiment 1, with each session including three stimulation types, with 4 trials per type. Participants received two stimulation types in Experiment 2, with 20 trials of a given stimulation type per session. Within-participant reliability was tested by repeating select sessions. This unique dataset supports a range of hypothesis testing including interactions of tDCS/tACS location and frequency, brain-state, physiology, fatigue, and cognitive performance.