Limited output transcranial electrical stimulation (LOTES-2017): Engineering principles, regulatory statutes, and industry standards for wellness, over-the-counter, or prescription devices with low risk. Download: PDF

Marom Bikson, Bhaskar Paneri, Andoni Mourdoukoutas, Zeinab Esmaeilpour, Bashar W. Badran, Robin Azzam, Devin Adair, Abhishek Datta, Xiao Hui Fang, Brett Wingeiner, Daniel Chao, Miguel Alonso-Alonso, Kiwon Lee, Helena Knotkova, Adam J. Woods, David Hagedorn, Doug Jeffery, James Giordano, William J. Tyler.

ABSTRACT:

We present device standards for low-power non-invasive electrical brain stimulation devices classified as limited output transcranial electrical stimulation (tES). Emerging applications of limited output tES to modulate brain function span techniques to stimulate brain or nerve structures, including transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), and trancranial pulsed current stimulation (tPCS), have engendered discussion on how access to technology  should be regulated. In regards to legal regulations and manufacturing standards for comparable technologies, a comprehensive framework already exists, including quality systems (QS), risk management, and (inter) national electrotechnical standards (IEC). In Part 1, relevant statutes are described for medical and wellness application. While agencies overseeing medical devices have broad jurisdiction, enforcement typically focuses on those devices with medical claims or posing significant risk. Consumer protections regarding responsible marketing and manufacture apply regardless. In Part 2 of this paper, we classify the electrical output performance of devices cleared by the United States Food and Drug Administration (FDA) including over-the-counter (OTC) and prescription electrostimulation devices, devices available for therapeutic or cosmetic purposes, and devices indicated for stimulationof the body or head. Examples include iontophoresis devices, powered muscle stimulators (PMS), cranial electrotheraphy stimulation (CES), and transcutaneous electrical nerve stimulation (TENS) devices. Spanning over 13 FDA product codes, more than 1200 electrical stimulators have been cleared for marketing since 1977. The output characteristics of conventional tDCS,tACS, and tPCS techniques are well below those of most FDA cleared devices, including devices that are available OTC and those intended for stimulation on the head. This engineering analysis demonstrates that with regard to output performance and standing regulation, the availability of tDCS, tACS, or tPCS to the public would not introduce risk, provided such devices are responsibly manufactured and legally marketed. In Part 3, we develop voluntary manufacturer guidance for limited output tES that is aligned with current regulatory standards. Based on established medical engineering and scientific principles, we outline a robust and transparent technical framework for ensuring limited output tES devices are designed to minimize risks, while also supporting access and innovation. Alongside applicable medical and government activities , this voluntary industry standard (LOTES-2017) further serves an important role in supporting informed decisions by the public.

 

ABSTRACT (PDF:download)
Positive emotional perceptions and healthy emotional intelligence (EI) are important for social
functioning. In this study, we investigated whether loving kindness meditation (LKM) combined
with anodal transcranial direct current stimulation (tDCS) would facilitate improvements in EI and
changes in affective experience of visual stimuli. LKM has been shown to increase positive
emotional experiences and we hypothesized that tDCS could enhance these effects. Eightyseven
undergraduates were randomly assigned to 30 minutes of LKM or a relaxation control
recording with anodal tDCS applied to the left dorsolateral prefrontal cortex (left dlPFC) or right
temporoparietal junction (right TPJ) at 0.1 or 2.0 milliamps. The primary outcomes were selfreported
affect ratings of images from the International Affective Picture System and EI as
measured by the Mayer, Salovey and Caruso Emotional Intelligence Test. Results indicated no
effects of training on EI, and no main effects of LKM, electrode placement, or tDCS current
strength on affect ratings. There was a significant interaction of electrode placement by meditation
condition (p = 0.001), such that those assigned to LKM and right TPJ tDCS, regardless of
current strength, rated neutral and positive images more positively after training. Results suggest
that LKM may enhance positive affective experience.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Neuromodulation: Technology at the Neural Interface, Clinical Research

Download PDF: Ezquerro_et_al-2017-Neuromodulation-_Technology_at_the_Neural_Interface

The Influence of Skin Redness on Blinding in Transcranial Direct Current Stimulation Studies: A Crossover Trial

Fernando Ezquerro, Adriano H. Moffa, Marom Bikson, Niranjan Khadka, Luana V. M. Aparicio, Bernardo de Sampaio-Junior, Felipe Fregni, Isabela M. Bensenor, Paulo A. Lotufo, Alexandre Costa Pereira, Andre R. Brunoni

Abstract:

Objective
To evaluate whether and to which extent skin redness (erythema) affects investigator blinding in transcranial direct current stimulation (tDCS) trials.
Material and Methods
Twenty-six volunteers received sham and active tDCS, which was applied with saline-soaked sponges of different thicknesses. High-resolution skin images, taken before and 5, 15, and 30 min after stimulation, were randomized and presented to experienced raters who evaluated erythema intensity and judged on the likelihood of stimulation condition (sham vs. active). In addition, semi-automated image processing generated probability heatmaps and surface area coverage of erythema. Adverse events were also collected.
Results
Erythema was present, but less intense in sham compared to active groups. Erythema intensity was inversely and directly associated to correct sham and active stimulation group allocation, respectively. Our image analyses found that erythema also occurs after sham and its distribution is homogenous below electrodes. Tingling frequency was higher using thin compared to thick sponges, whereas erythema was more intense under thick sponges.
Conclusions
Optimal investigator blinding is achieved when erythema after tDCS is mild. Erythema distribution under the electrode is patchy, occurs after sham tDCS and varies according to sponge thickness. We discuss methods to address skin erythema-related tDCS unblinding.

Full PDF: Erythema and tDCS

figure_panel_with_subtitle

Congrats on Yu (Andy) Huang, Marom Bikson, and Lucas Parra’s paper on TES model validation accepted to be published on eLife. Also thank Anli Liu’s team from NYU School of Medicine for all the experimental recordings.

Measurements and models of electric fields in the in vivo human brain during transcranial electric stimulation

Here is the link to the LINK, and a summary video.

OR Download the PDF here: e18834-download (3)  and the associated Commentary here: e25812-download

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Remotely Supervised Transcranial Direct Current Stimulation Increases the Benefit of At-Home Cognitive Training in Multiple Sclerosis

Neuromodulation. 2017 Feb 22. doi: 10.1111/ner.12583. [Epub ahead of print]
PMID: 28225155

Leigh Charvet, PhD; Michael Shaw, BS; Bryan Dobbs, MS; Ariana Frontario, BS; Kathleen Sherman, MS; Marom Bikson, PhD; Abhishek Datta, PhD; Lauren Krupp, MD; Esmail Zeinapour, MS; Margaret Kasschau, BS

Full paper PDF: 10.1111@ner.12583

Objective: To explore the efficacy of remotely-supervised transcranial direct current stimulation (RS-tDCS) paired with cognitive training (CT) exercise in participants with multiple sclerosis (MS). Methods: In a feasibility study of RS-tDCS in MS, participants completed ten sessions of tDCS paired with CT (1.5 mA 3 20 min, dorsolateral prefrontal cortex montage). RS-tDCS participants were compared to a control group of adults with MS who underwent ten 20-min CT sessions through the same remotely supervised procedures. Cognitive outcomes were tested by composite scores measuring change in performance on standard tests (Brief International Cognitive Assessment in MS or BICAMS), basic attention (ANT-I Orienting and Attention Networks, Cogstate Detection), complex attention (ANT-I Executive Network, Cogstate Identification and One-Back), and intra-individual response variability (ANT-I and Cogstate identification; sensitive markers of disease status). Results: After ten sessions, the tDCS group (n 5 25) compared to the CT only group (n 5 20) had significantly greater improvement in complex attention (p 5 0.01) and response variability (p 5 0.01) composites. The groups did not differ in measures of basic attention (p 5 0.95) or standard cognitive measures (p 5 0.99). Conclusions: These initial findings indicate benefit for RS-tDCS paired with CT in MS. Exploratory analyses indicate that the earliest tDCS cognitive benefit is seen in complex attention and response variability. Telerehabilitation using RS-tDCS combined with CT may lead to improved outcomes in MS.

Higher-order power harmonics of pulsed electrical stimulation modulates corticospinal contribution of peripheral nerve stimulation.
Chen CF, Bikson M, Chou LW, Shan C, Khadka N, Chen WS, Fregni F.
Nature Sci Rep. 2017 Mar 3;7:43619. doi: 10.1038/srep43619.
PMID: 28256638  Download Full Paper: srep43619

Abstract: It is well established that electrical-stimulation frequency is crucial to determining the scale of induced neuromodulation, particularly when attempting to modulate corticospinal excitability. However, the modulatory effects of stimulation frequency are not only determined by its absolute value but also by other parameters such as power at harmonics. The stimulus pulse shape further influences parameters such as excitation threshold and fiber selectivity. The explicit role of the power in these harmonics in determining the outcome of stimulation has not previously been analyzed. In this study, we adopted an animal model of peripheral electrical stimulation that includes an amplitude-adapted pulse train which induces force enhancements with a corticospinal contribution. We report that the electrical-stimulation-induced force enhancements were correlated with the amplitude of stimulation power harmonics during the amplitude-adapted pulse train. This is a pilot, but important first demonstration that power at high order harmonics in the frequency spectrum of electrical stimulation pulses may contribute to neuromodulation, thus warrant explicit attention in therapy design and analysis.

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Higher-order power harmonics of pulsed electrical stimulation modulates corticospinal contribution of peripheral nerve stimulation.
Chen CF, Bikson M, Chou LW, Shan C, Khadka N, Chen WS, Fregni F.
Nature Sci Rep. 2017 Mar 3;7:43619. doi: 10.1038/srep43619.
PMID: 28256638  Download Full Paper: srep43619

Abstract: It is well established that electrical-stimulation frequency is crucial to determining the scale of induced neuromodulation, particularly when attempting to modulate corticospinal excitability. However, the modulatory effects of stimulation frequency are not only determined by its absolute value but also by other parameters such as power at harmonics. The stimulus pulse shape further influences parameters such as excitation threshold and fiber selectivity. The explicit role of the power in these harmonics in determining the outcome of stimulation has not previously been analyzed. In this study, we adopted an animal model of peripheral electrical stimulation that includes an amplitude-adapted pulse train which induces force enhancements with a corticospinal contribution. We report that the electrical-stimulation-induced force enhancements were correlated with the amplitude of stimulation power harmonics during the amplitude-adapted pulse train. This is a pilot, but important first demonstration that power at high order harmonics in the frequency spectrum of electrical stimulation pulses may contribute to neuromodulation, thus warrant explicit attention in therapy design and analysis.

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 Scientists, entrepreneurs in Chicago area tackle ‘brain hacking’

March 3, 2017, by Ted Gregory

Link to article

Selection: “Marom Bikson is optimistic and pragmatic. A biomedical engineering professor and co-director of Neural Engineering at the City College of New York, Bikson said it is clear that tDCS can change the brain. Many prospective users are unwilling to wait for lengthy human trials and related research before trying the technology.

“Among scientists who are incredulous or skeptical, the concern is often that we’re moving too fast,” Bikson said. But people who are suffering from depression, chronic pain and cognitive decline “have a different time scale,” he said. “They don’t have 10 years, and I don’t blame them for looking for alternatives.”

 

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