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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Minimal heating at the Skin surface during transcranial direct current stimulation (tDCS)

Khadka N.; Zannou A.L.; Zunura F.; Truong D.Q.; Dmochowski J.; Bikson M. 2017. Minimal Heating at the Skin Surface During Transcranial Direct Current Stimulation.

Neuromodulation 2017; E-pub ahead of print. DOI:10.1111/ner.12554

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Abstract

Objective:
To assess if transcranial direct current stimulation (tDCS) produces a temperature change at the skin surface, if any change is stimulation polarity (anode or cathode) specific, and the contribution of passive heating (joule heat) or blood flow on such change.

Material and Methods:
Temperature differences (ΔTs) in an agar phantom study and an in vivo study (forearm stimulation) including 20 volunteers with both experimental measures and finite element method (FEM) multiphysics prediction (current flow and bioheat) models of skin comprising three tissue layers (epidermis, dermis, and subcutaneous layer with blood perfusion) or of the phantom for active stimulation and control cases were compared. Temperature was measured during pre, post, and stimulation phases for both phantom and subject’s forearms using thermocouples.

Results:
In the phantom, ΔT under both anode and cathode, compared to control, was not significantly different and less than 0.1°C. Stimulation of subjects resulted in a gradual increase in temperature under both anode and cathode electrodes, compared to control (at t = 20 min: ΔTanode = 0.9°C, ΔTcathode = 1.1°C, ΔTcontrol = 0.05°C). The FEM phantom model predicted comparable maximum ΔT of 0.27°C and 0.28°C (at t = 20 min) for the control and anode/cathode cases, respectively. The FEM skin model predicted a maximum ΔT at t = 20 min of 0.98°C for control and 1.36°C under anode/cathode electrodes.

Conclusions:
Taken together, our results indicate a moderate and nonhazardous increase in temperature at the skin surface during 2 mA tDCS that is independent of polarity, and results from stimulation induced blood flow rather than joule heat.

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Spatial and polarity precision of concentric high-definition transcranial direct current stimulation (HD-tDCS)

IOPScience: Physics in Medicine and Biology, Volume 61, Number 12, 4506-4521, 2016, Click here for full paper

Mahtab Alam, Dennis Q Truong, Niranjan Khadka and Marom Bikson

Abstract:

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique that applies low amplitude current via electrodes placed on the scalp. Rather than directly eliciting a neuronal response, tDCS is believed to modulate excitability—enhancing or suppressing neuronal activity in regions of the brain depending on the polarity of stimulation. The specificity of tDCS to any therapeutic application derives in part from how electrode configuration determines the brain regions that are stimulated. Conventional tDCS uses two relatively large pads (>25 cm2) whereas high-definition tDCS (HD-tDCS) uses arrays of smaller electrodes to enhance brain targeting. The 4  ×  1 concentric ring HD-tDCS (one center electrode surrounded by four returns) has been explored in application where focal targeting of cortex is desired. Here, we considered optimization of concentric ring HD-tDCS for targeting: the role of electrodes in the ring and the ring’s diameter. Finite element models predicted cortical electric field generated during tDCS. High resolution MRIs were segmented into seven tissue/material masks of varying conductivities. Computer aided design (CAD) model of electrodes, gel, and sponge pads were incorporated into the segmentation. Volume meshes were generated and the Laplace equation ($\nabla $  centerdot (σ $\nabla $  V)  =  0) was solved for cortical electric field, which was interpreted using physiological assumptions to correlate with stimulation and modulation. Cortical field intensity was predicted to increase with increasing ring diameter at the cost of focality while uni-directionality decreased. Additional surrounding ring electrodes increased uni-directionality while lowering cortical field intensity and increasing focality; though, this effect saturated and more than 4 surround electrode would not be justified. Using a range of concentric HD-tDCS montages, we showed that cortical region of influence can be controlled while balancing other design factors such as intensity at the target and uni-directionality. Furthermore, the evaluated concentric HD-tDCS approaches can provide categorical improvements in targeting compared to conventional tDCS. Hypothesis driven clinical trials, based on specific target engagement, would benefit by this more precise method of stimulation that could avoid potentially confounding brain regions.

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Principles of Within Electrode Current Steering (WECS)

Journal of Medical Devices, Vol. 9 / 020947-1, 2015, Click here to access full paper

Niranjan Khadka, Dennis Q. Truong, Marom Bikson

Abstract

Within Electrode Current Steering (WECS) is a novel method that enhances reliability and tolerability of tDCS. The underlying assumption of WECS is steering current within electrodes but without altering current distribution in brain target. Through an exemplary case example of a realistic electrode and head geometry (FEM), we demonstrated how current flow in the brain is independent of current steering at the electrode. Three current split cases (even, partially uneven, and fully uneven), keeping total current (1 mA) fixed within the electrodes are tested. At the electrode-assembly interface with the skin, the current density distribution varied only incrementally across conditions (e.g. less than would be expected with even minor changes in electrode assembly or skin properties. There was no difference in the predicted electric filed at the brain target under all three cases. Thus, with such electrode assembly design, current steering to any functional electrode would not significantly increase current density in the skin (enhance tolerability during tDCS).

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Figure: FEM analysis of electrode assembly to validate the underlying assumption of within electrode current steering. (A) Represents a montage with electrode assembly. (B) “Even”, “Partially Uneven”, and “Fully Uneven” current injection model through metal rivets of an electrode assembly keeping total current constant. (C) Illustrates streamline current flow from each metal rivets under all three current injection conditions. (D) Current density observed at the scalp electrode interface. (E) Presents an electric field distribution found in the brain targer.

BME Day, May 01, 2015, Department of Biomedical Engineering, CCNY

Wireless Pulse Oximeter (WiPOX): Its Clinical Implications and Challenges

The WiPOX provides a tool for surgeons to objectively and reliably measure tissue viability during surgery rather than rely solely on their subjective visual inspection. Tissue ischemia is a major cause of wound dehiscence or anastomotic leakage resulting in significant morbidity and mortality occuring at a rate of 15 to 25%. Although measurement of systemic blood oxygenation status by finger-tip pulse oximetery is a mandatory requirement for every anesthetized patient, there is no standadrad procedure for intra-operative measurement of internal tissue oxygenation following complex resections and reconstructions.

Based on clinical experience gained in our trials, we present here the design of a second generation WiPOX that includes a reticulated pressure-sensitive head serving two related functions. First, the often-restricted and sensitive environment in which the device is employed constrains both the angle of approach and visibility, necessitating a self- correcting reticulated swiveling head that acts to improve the contact angle between the sensor head and the tissue. Second, because the devices is hand-held, the pressure on the tissue (often a membrane) is determined by the operator; too little pressure produces poor signal to noise ratio (SNR) while too much pressure can occlude blood flow, also reducing SNR and possibly yielding erroneously low oxygenation measurements. To address this, our sensor head includes a novel mounting for multiple “balloon” style pressure sensors that provide feedback on tissue contact pressure and contact angle. The reticulated head and pressure sensor features function in tandem to improve tissue contact and ensure
reliable measurements.

VENUE: Department of Biomedical Engineering, CCNY, ST 402

Niranjan Khadka presented a poster at the Minnesota Neuromodulation Symposium

Poster Title: Principles of Within Electrode Current Steering(WECS)

KhadkaBiksonWECS

Department of Biomedical Engineering, The City College of New York, CUNY, 160 Convent Ave, New York, 10031, USA

Within Electrode Current Steering (WECS), a novel method, applies to non-invasive electrical stimulation with two or more electrodes to enhance reliability and tolerability during tDCS. The underlying assumption of WECS is steering current within electrodes (to compensate for any non-ideal conditions at the surface), but without altering current distribution in the brain target. This technology leverages our technique for independently isolating electrode impedance and over-potential during multi-channel stimulation. Through an exemplary case example of a realistic electrodes (metal-rivets embedded in an electrolyte (saline or gel)) and head geometry (FEM), we demonstrated how current flow in brain is independent of current steering at the electrode. Three current split cases (even, partially uneven, and fully uneven), keeping total current (1 mA) fixed within the electrodes are tested. At the electrode-assembly interface with the skin, the current density distribution varied only incrementally across conditions (e.g. less than would be expected) with even minor changes in electrode assembly or skin properties. There was no difference in the predicted electric filed at the brain target under all three cases. Thus, with such electrode assembly design, current steering to any functional electrode would not significantly increase current density in the skin; hence, not effecting tolerability.

Date & time: April 17, 2015 11:30-1:00 pm

Venue: University of Minnesota, Twin City, Minnesota

WECS

Niranjan Khadka presented a poster at the DMD Conference.

Poster Title: Design of Wireless Intraoperative Pulse Oximeter with Reticulated Pressure Sensitive Head

Link: KhadkaBiksonWiPOX

In order to provide a surgical tool that objectively and reliably measure tissue viability during surgery, we developed and validated a first generation compact handheld device for real time wireless monitoring of SPO2. Through the application of pressure sensor (provide feedback of real-time contact conditions of the device), reticulated shaft (facilitate flat contact with the tissue surface that are less visible), and systemic pulse rate input to signal tissue oxygenation through signal processing, this invention will enable surgeons to make treatment decision and measure the efficacy of the therapeutic interventions in real-time.

Date & time: April 15, 2015 5:30 – 7:00

Venue: McNamara Alumni Center, University of Minnesota, Minneapolis, MN

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