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

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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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 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.”

 

Shown equipment by Soterix Medical.

 

 

Brain-Hackers Vie to Enhance Human Performance

Wall Street Journal, Feb 24, 2017

By TOMIO GERON

Full article link

Abridged article:

Hacking software or network-connected devices is so 21st century. A new crop of forward-thinking entrepreneurs wants to hack the ultimate computer: the brain.

Enhancing or altering the brain with technology may sound like a concept for the cyborgs of science fiction, but Silicon Valley startups are already at it—with venture capitalists’ backing. A range of noninvasive wearable devices have hit the consumer market using electrical stimulation to sharpen physical and mental performance or to improve relaxation….

Interest in brain devices fits squarely within Silicon Valley’s ever-growing do-it-yourself biohacking and quantified-self movement, where people obsessively measure everything from their carbohydrate intake to mental acuity to sleep patterns. And the trend ties in with popular millennial pursuits like meditation, mindfulness and nontraditional remedies including nootropics.

In Silicon Valley, where tech executives are always seeking an edge, brain hackers have found a willing market for experimentation as a natural extension of that impulse.

Los Gatos, Calif.-based Thync has raised about $23 million from Noosphere Ventures, Khosla Ventures and Andreessen Horowitz, according to PitchBook. The company says its $199 device can improve sleep and reduce stress. It second version, due out this spring, attaches to the back of the neck instead of the head….

Several startups’ devices rely on sending electric pulses into the brain, a process called tDCS that hasn’t been approved for medical use in the U.S. While that stimulation has been found safe in a laboratory environment, the benefits in consumer devices are unclear because of a lack of independent studies, according to Rachel Wurzman, a researcher at the University of Pennsylvania’s Laboratory for Cognition and Neural Stimulation….

Startup Halo Neuroscience’s headset aims to improve athletic performance. The device sends electric fields into the brain’s motor cortex, creating a state of “hyperplasticity” which, when combined with athletic training, helps the brain more quickly build circuitry to interact with muscles, improving technique and explosiveness, said co-founder and Chief Executive Daniel Chao.

Users wear the $749 device, which looks like a pair of headphones, for 20 minutes before a workout. The San Francisco company has raised $9 million from Lux Capital, Andreessen Horowitz, Jazz Venture Partners, SoftTech VC and Xfund. Its athlete-endorsers include Demario Davis of the Cleveland Browns and T.J. Carrie of the Oakland Raiders.

Halo has focused on professional athletes but is targeting consumers who are performance athletes or enthusiasts, as opposed to casual athletes, said Mr. Chao, who previously worked at a medical-device startup that used electric stimulation to treat epilepsy….

While the use of brain stimulation is based on genuine science, it doesn’t necessarily back up marketing by consumer brands, said Marom Bikson, a professor of biomedical engineering at the City College of New York, who has done studies on Thync and co-founded medical-device startup Soterix Medical.

“There’s unquestionably scientific studies done in controlled environments that suggest that tDCS can change cognition and change how people think or can change learning,” Mr. Bikson said. “Some claims may be made by some companies that are maybe more advanced than where a lot of the scientists may be comfortable.”

BN-SF732_Halosp_GR_20170223192540

Mechanisms and Effects of Transcranial Direct Current Stimulation

Dose-Response: An International Journal January-March 2017:1-22 DOI: 10.1177/1559325816685467

James Giordano, Marom Bikson, Emily S. Kappenman, Vincent P. Clark, H. Branch Coslett, Michael R. Hamblin, Roy Hamilton, Ryan Jankord, Walter J. Kozumbo, R. Andrew McKinley, Michael A. Nitsche, J. Patrick Reilly, Jessica Richardson, Rachel Wurzman, and Edward Calabrese

Abstract: The US Air Force Office of Scientific Research convened a meeting of researchers in the fields of neuroscience, psychology, engineering, and medicine to discuss most pressing issues facing ongoing research in the field of transcranial direct current stimulation (tDCS) and related techniques. In this study, we present opinions prepared by participants of the meeting, focusing on the most promising areas of research, immediate and future goals for the field, and the potential for hormesis theory to inform tDCS research. Scientific, medical, and ethical considerations support the ongoing testing of tDCS in healthy and clinical popu- lations, provided best protocols are used to maximize safety. Notwithstanding the need for ongoing research, promising appli- cations include enhancing vigilance/attention in healthy volunteers, which can accelerate training and support learning. Commonly, tDCS is used as an adjunct to training/rehabilitation tasks with the goal of leftward shift in the learning/treatment effect curves. Although trials are encouraging, elucidating the basic mechanisms of tDCS will accelerate validation and adoption. To this end, biomarkers (eg, clinical neuroimaging and findings from animal models) can support hypotheses linking neurobiological mechanisms and behavioral effects. Dosage can be optimized using computational models of current flow and understanding dose–response. Both biomarkers and dosimetry should guide individualized interventions with the goal of reducing variability. Insights from other applied energy domains, including ionizing radiation, transcranial magnetic stimulation, and low-level laser (light) therapy, can be prudently leveraged.

Download: Final OnLine Proceedings – Dose Response Journal

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Computational models of Bitemporal, Bifrontal and Right Unilateral ECT predict differential stimulation of brain regions associated with efficacy and cognitive side effects.

Bai S, Gálvez V, Dokos S, Martin D, Bikson M, Loo C.
Eur Psychiatry. 2016 Dec 29;41:21-29. doi: 10.1016/j.eurpsy.2016.09.005. [Epub ahead of print]
PMID: 28049077

Full paper: 10.1016@j.eurpsy.2016.09.005

Abstract: 

BACKGROUND: Extensive clinical research has shown that the efficacy and cognitive outcomes of electroconvulsive therapy (ECT) are determined, in part, by the type of electrode placement used. Bitemporal ECT (BT, stimulating electrodes placed bilaterally in the frontotemporal region) is the form of ECT with relatively potent clinical and cognitive side effects. However, the reasons for this are poorly understood.
OBJECTIVE: This study used computational modelling to examine regional differences in brain excitation between BT, Bifrontal (BF) and Right Unilateral (RUL) ECT, currently the most clinically-used ECT placements. Specifically, by comparing similarities and differences in current distribution patterns between BT ECT and the other two placements, the study aimed to create an explanatory model of critical brain sites that mediate antidepressant efficacy and sites associated with cognitive, particularly memory, adverse effects.
METHODS: High resolution finite element human head models were generated from MRI scans of three subjects. The models were used to compare differences in activation between the three ECT placements, using subtraction maps.
RESULTS AND CONCLUSION: In this exploratory study on three realistic head models, Bitemporal ECT resulted in greater direct stimulation of deep midline structures and also left temporal and inferior frontal regions. Interpreted in light of existing knowledge on depressive pathophysiology and cognitive neuroanatomy, it is suggested that the former sites are related to efficacy and the latter to cognitive deficits. We hereby propose an approach using binarised subtraction models that can be used to optimise, and even individualise, ECT therapies

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