New Pub: Finite Element Method Model Mapping Focal Intracranial Cooling

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.

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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.

Marom Bikson
New Book Chapter: Noninvasive Electrical Brain Stimulation of the Central Nervous System

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.

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New paper: tES for Psychiatric Disorders: A Primer

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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Marom Bikson
New publication: Transcranial Focused Ultrasound in Alzheimer’s Disease

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

Marom Bikson
CCNY Neural Engineering at NANS 2022

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

Marom Bikson
IEEE Spectrum features our work on COVID treatments

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.”

Marom Bikson
New Book Chapter: Transcranial Electrical Stimulation (tES)

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.

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CCNY Neural Engineering at the International Brain Stimulation Conference

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 >>

Marom Bikson
New paper: Weak DCS causes a relatively strong cumulative boost of synaptic plasticity with spaced learning

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.

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Dr. Bikson lectures to Cardiff University

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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Marom Bikson
New Paper: Dataset of concurrent EEG, ECG, and behavior with multiple doses of transcranial electrical stimulation

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.

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New Book Chapter: Transcranial electrical stimulation devices

Transcranial electrical stimulation devices

Dennis Q. Truong, Niranjan Khadka, Angel V. Peterchev, and Marom Bikson

Oxford University Press | (2021) | The Oxford Handbook of Transcranial Stimulation, Second Edition 2 2-55 | 10.1093/oxfordhb/9780198832256.013.2

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Abstract:

Transcranial electrical stimulation (tES) devices apply electrical waveforms through electrodes placed on the scalp to modulate brain function. This chapter describes the principles, types, and components of tES devices as well as practical considerations for their use. All tES devices include a waveform generator, electrodes, and an adhesive or headgear to position the electrodes. tES dose is defined by the size and position of electrodes, and the waveform, duration, and intensity of the current. Many sub-classes of tES are named based on dose. This chapter focuses on low intensity tES, which includes transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), and transcranial pulsed current stimulation (tPCS). tES electrode types are reviewed, including electrolyte-soaked sponge, adhesive hydrogel, high-definition, hand-held solid metal, free paste on electrode, and dry. Computational models support device design and individual targeting. The tolerability of tES is protocol specific, and medical grade devices minimize risk.

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New Paper: Direct Current Stimulation Disrupts Endothelial Glycocalyx and Tight Junctions of the Blood-Brain Barrier in vitro

New paper in Frontiers in Cell and Developmental Biology

Direct Current Stimulation Disrupts Endothelial Glycocalyx and Tight Junctions of the Blood-Brain Barrier in vitro

Yifan Xia, Yunfei Li, Wasem Khalid, Marom Bikson & Bingmei M. Fu

Frontiers in Cell and Developmental Biology | (2021) 9 | https://doi.org/10.3389/fcell.2021.731028

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Abstract: Transcranial direct current stimulation (tDCS) is a non-invasive physical therapy to treat many psychiatric disorders and to enhance memory and cognition in healthy individuals. Our recent studies showed that tDCS with the proper dosage and duration can transiently enhance the permeability (P) of the blood-brain barrier (BBB) in rat brain to various sized solutes. Based on the in vivo permeability data, a transport model for the paracellular pathway of the BBB also predicted that tDCS can transiently disrupt the endothelial glycocalyx (EG) and the tight junction between endothelial cells. To confirm these predictions and to investigate the structural mechanisms by which tDCS modulates P of the BBB, we directly quantified the EG and tight junctions of in vitro BBB models after DCS treatment. Human cerebral microvascular endothelial cells (hCMECs) and mouse brain microvascular endothelial cells (bEnd3) were cultured on the Transwell filter with 3 μm pores to generate in vitro BBBs. After confluence, 0.1–1 mA/cm2 DCS was applied for 5 and 10 min. TEER and P to dextran-70k of the in vitro BBB were measured, HS (heparan sulfate) and hyaluronic acid (HA) of EG was immuno-stained and quantified, as well as the tight junction ZO-1. We found disrupted EG and ZO-1 when P to dextran-70k was increased and TEER was decreased by the DCS. To further investigate the cellular signaling mechanism of DCS on the BBB permeability, we pretreated the in vitro BBB with a nitric oxide synthase (NOS) inhibitor, L-NMMA. L-NMMA diminished the effect of DCS on the BBB permeability by protecting the EG and reinforcing tight junctions. These in vitro results conform to the in vivo observations and confirm the model prediction that DCS can disrupt the EG and tight junction of the BBB. Nevertheless, the in vivo effects of DCS are transient which backup its safety in the clinical application. In conclusion, our current study directly elucidates the structural and signaling mechanisms by which DCS modulates the BBB permeability.

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