Download: PDF published in Neuromodulation – DOI

Helena Knotkova, Alexa Riggs, Destiny Berisha, Helen Borges, Henry Bernstein, Vaishali Patel, Dennis Q. Truong, Gozde Unal, Denis Arce, Abhishek Datta, Marom Bikson

Abstract

Objectives

Non‐invasive transcranial direct current stimulation (tDCS) over the motor cortex is broadly investigated to modulate functional outcomes such as motor function, sleep characteristics, or pain. The most common montages that use two large electrodes (25–35 cm2) placed over the area of motor cortex and contralateral supraorbital region (M1‐SO montages) require precise measurements, usually using the 10–20 EEG system, which is cumbersome in clinics and not suitable for applications by patients at home. The objective was to develop and test novel headgear allowing for reproduction of the M1‐SO montage without the 10–20 EEG measurements, neuronavigation, or TMS.

Materials and Methods

Points C3/C4 of the 10–20 EEG system is the conventional reference for the M1 electrode. The headgear was designed using an orthogonal, fixed‐angle approach for connection of frontal and coronal headgear components. The headgear prototype was evaluated for accuracy and replicability of the M1 electrode position in 600 repeated measurements compared to manually determined C3 in 30 volunteers. Computational modeling was used to estimate brain current flow at the mean and maximum recorded electrode placement deviations from C3.

Results

The headgear includes navigational points for accurate placement and assemblies to hold electrodes in the M1‐SO position without measurement by the user. Repeated measurements indicated accuracy and replicability of the electrode position: the mean [SD] deviation of the M1 electrode (size 5 × 5 cm) from C3 was 1.57 [1.51] mm, median 1 mm. Computational modeling suggests that the potential deviation from C3 does not produce a significant change in brain current flow.

Conclusions

The novel approach to M1‐SO montage using a fixed‐angle headgear not requiring measurements by patients or caregivers facilitates tDCS studies in home settings and can replace cumbersome C3 measurements for clinical tDCS applications.

Download: PDF published in Brain Stimulation – DOI

Jaclyn Reckow, Annalise Rahman-Filipiak, Sarah Garcia, Stephen Schlaefflin, Oliver Calhoun, Alexandre F. DaSilva, Marom Bikson, Benjamin M. Hampstead

Abstract

Background

Transcranial direct current stimulation (tDCS) is an in-demand form of neuromodulation generally regarded as safe and well tolerated. However, few studies have examined the safety, tolerability, or blinding of High Definition (HD-) tDCS, especially in older adults and at stimulation intensities of 2 milliamps (mA) or greater.

Objective

We examined the rates of serious adverse events and common side effects to establish safety and tolerability, respectively, in HD-tDCS. Blinding was evaluated using participants’ accuracy in correctly stating their condition (i.e., active or sham).

Methods

The sample included 101 older adults (Mage = 69.69, SD = 8.33; Meduc = 16.27, SD = 2.42) who participated in our double blind randomized controlled studies or in case studies that used HD-tDCS for 20–30 min at 2 mA (n = 66, 31 active) or 3 mA (n = 35, 20 active). Participants completed a standardized side effect questionnaire and were asked whether they received active or sham stimulation at the end of each session.

Results

There were no serious adverse events and no participants withdrew, suggesting that HD-tDCS meets basic safety parameters. Tolerability was comparable between active and sham HD-tDCS regardless of intensity (2 mA and 3 mA) in first session (allp > .09). Tingling was the most commonly endorsed item (59% active; 56% sham) followed by burning sensation (51% active; 50% sham), the majority of which were mild in nature. “Severe” ratings were reported in fewer than 4% of sessions. Blinding appeared adequate since there were no significant group differences between individuals correctly stating their stimulation condition (χ2 = 0.689, p = .679). The above tolerability and blinding findings generally persisted when multiple session data (i.e., 186 total sessions) were considered.

Conclusions

HD-tDCS appears well-tolerated and safe with effective sham-control in older adults, even at 3 mA. These data support the use of HD-tDCS in randomized controlled trials and clinical translation efforts.

Download: PDF published in Brain Stimulation – DOI

Yeowool Huh, Dahee Jung, Taeyoon Seo, Sukkyu Sun, Su Hyun Kim, Hyewhon Rhim, Sooyoung Chung, Chong-Hyun Kim, Youngwoo Kwon, Marom Bikson, Yong-an Chung, Jeansok J. Kim, Jeiwon Cho

Abstract

The bursting pattern of thalamocortical (TC) pathway dampens nociception. Whether brain stimulation mimicking endogenous patterns can engage similar sensory gating processes in the cortex and reduce nociceptive behaviors remains uninvestigated. We investigated the role of cortical parvalbumin expressing (PV) interneurons within the TC circuit in gating nociception and their selective response to TC burst patterns. We then tested if transcranial magnetic stimulation (TMS) patterned on endogenous nociceptive TC bursting modulate nociceptive behaviors. The switching of TC neurons between tonic (single spike) and burst (high frequency spikes) firing modes may be a critical component in modulating nociceptive signals. Deep brain electrical stimulation of TC neurons and immunohistochemistry were used to examine the differential influence of each firing mode on cortical PV interneuron activity. Optogenetic stimulation of cortical PV interneurons assessed a direct role in nociceptive modulation. A new TMS protocol mimicking thalamic burst firing patterns, contrasted with conventional continuous and intermittent theta burst protocols, tested if TMS patterned on endogenous TC activity reduces nociceptive behaviors in mice. Immunohistochemical evidence confirmed that burst, but not tonic, deep brain stimulation of TC neurons increased the activity of PV interneurons in the cortex. Both optogenetic activation of PV interneurons and TMS protocol mimicking thalamic burst reduced nociceptive behaviors. Our findings suggest that burst firing of TC neurons recruits PV interneurons in the cortex to reduce nociceptive behaviors and that neuromodulation mimicking thalamic burst firing may be useful for modulating nociception.

Conference overview:  Technology creation and the discovery of new treatments indications in neuromodulation is accelerating. Non-invasive and invasive technologies are moving rapidly from bench-side to bedside, even as renewed focus on mechanisms of actions (target engagement) drive basic and clinical research. Tools from fields of artificial intelligence and machine learning, along with medical wearables and apps, are disrupting traditional models of clinical trials and treatment.

From August 24-26 2018 in New York City join thought leaders from medicine, academia, and industry, for the most dynamic conference on the future of neuromodulation. The joint meeting of the 2018 NYC Neuromodulation Conference and NANS Summer Series is produced by neuromodec.com and the North American Neuromodulation Society (NANS).

Conference website

The Toddler Cane, a medical device designed at the CCNY Neural Engineering lab, featured in “Photo Finish” section of Crain’s New York. Toddler Canes are available for free at SafeToddles.

The Toddler Cane is the first and only hands-free cane for blind and visually impaired toddlers. The Toddler Cane was invented by Dr. Grace Ambrose-Zaken of CUNY Hunter College and designed in Dr. Marom Bikson’s lab by Henry Bernstein and Mohamad FallahRad.

Watch the CBS New York segment with Dr. Max Gomez here

Watch the CUNY video here

You can support free toddler canes here at Safe Toddles

Download: PDF published in Brain Stimulation – DOI

Pratik Y. Chhatbar, Steven A. Kautz, Istvan Takacs, Nathan C. Rowland, Gonzalo J. Revuelta, Mark S. George, Marom Bikson, Wuwei Feng

Abstract: Transcranial direct current stimulation (tDCS) is a promising brain modulation technique for several disease conditions. With this technique, some portion of the current penetrates through the scalp to the cortex and modulates cortical excitability, but a recent human cadaver study questions the amount. This insufficient intracerebral penetration of currents may partially explain the inconsistent and mixed results in tDCS studies to date. Experimental validation of a transcranial alternating current stimulation-generated electric field (EF) in vivo has been performed on the cortical (using electrocorticography, ECoG, electrodes), subcortical (using stereo electroencephalography, SEEG, electrodes) and deeper thalamic/subthalamic levels (using DBS electrodes). However, tDCS-generated EF measurements have never been attempted. Hypothesis: We aimed to demonstrate that tDCS generates biologically relevant EF as deep as the subthalamic level in vivo. Patients with movement disorders who have implanted deep brain stimulation (DBS) electrodes serve as a natural experimental model for thalamic/subthalamic recordings of tDCS-generated EF. We measured voltage changes from DBS electrodes and body resistance from tDCS electrodes in three subjects while applying direct current to the scalp at 2 mA and 4 mA over two tDCS montages. Voltage changes at the level of deep nuclei changed proportionally with the level of applied current and varied with different tDCS montages. Our findings suggest that scalp-applied tDCS generates biologically relevant EF. Incorporation of these experimental results may improve finite element analysis (FEA)-based models.

Download: PDF published in Frontiers in Psychiatry – DOI

Won Hee Lee, Nigel I. Kennedy, Marom Bikson, and Sophia Frangou

Abstract

We use auditory verbal hallucinations (AVH) to illustrate the challenges in defining and assessing target engagement in the context of transcranial direct current stimulation (tDCS) for psychiatric disorders. We defined the target network as the cluster of regions of interest (ROIs) that are consistently implicated in AVH based on the conjunction of multimodal meta-analytic neuroimaging data. These were prescribed in the New York Head (a population derived model) and head models of four single individuals. We appraised two potential measures of target engagement, tDCS-induced peak electric field strength and tDCS-modulated volume defined as the percentage of the volume of the AVH network exposed to electric field magnitude stronger than the postulated threshold for neuronal excitability. We examined a left unilateral (LUL) montage targeting the prefrontal cortex (PFC) and temporoparietal junction (TPJ), a bilateral (BL) prefrontal montage, and a 2 × 1 montage targeting the left PFC and the TPJ bilaterally. Using computational modeling, we estimated the peak electric field strength and modulated volume induced by each montage for current amplitudes ranging 1–4 mA. We found that the LUL montage was inferior to both other montages in terms of peak electric field strength in right-sided AVH-ROIs. The BL montage was inferior to both other montages in terms of modulated volume of the left-sided AVH-ROIs. As the modulated volume is non-linear, its variability between montages reduced for current amplitudes above 3 mA. These findings illustrate how computational target engagement for tDCS can be tailored to specific networks and provide a principled approach for future study design.

Dr. Marom Bikson is interviewed as part of a article on brain stimulation in Scientific American. link

Dr Marom Bikson interviewed in “The Truth and Electrical Brain Stimulation” in LifeHacker Jan 18, 2018.

Callesen H, Habelt B, Wieske F, Jackson M, Khadka N, Mattei D, Bernhardt N, Heinz A, Liebetanz D, Bikson M, Padberg F, Hadar R, Nitsche MA, Winter C

---

Download: PDF published in Nature Translational Psychiatry – DOI

Abstract

Involuntary movements as seen in repetitive disorders such as Tourette Syndrome (TS) results from cortical hyperexcitability that arise due to striato-thalamo-cortical circuit (STC) imbalance. Transcranial direct current stimulation (tDCS) is a stimulation procedure that changes cortical excitability, yet its relevance in repetitive disorders such as TS remains largely unexplored. Here, we employed the dopamine transporter-overexpressing (DAT-tg) rat model to investigate behavioral and neurobiological effects of frontal tDCS. The outcome of tDCS was pathology dependent, as anodal tDCS decreased repetitive behavior in the DAT-tg rats yet increased it in wild-type (wt) rats. Extensive deep brain stimulation (DBS) application and computational modeling assigned the response in DAT-tg rats to the sensorimotor pathway. Neurobiological assessment revealed cortical activity changes and increase in striatal inhibitory properties in the DAT-tg rats. Our findings show that tDCS reduces repetitive behavior in the DAT-tg rat through modulation of the sensorimotor STC circuit. This sets the stage for further investigating the usage of tDCS in repetitive disorders such as TS.

Download: PDF published in Brain Stimulation

doi.org/10.1016/j.brs.2017.12.008

Marom Bikson, Andre R. Brunoni, Leigh E. Charvet, Vincent P. Clark, Leonardo G. Cohen, Zhi-De Deng, Jacek Dmochowski, Dylan J. Edwards, Flavio Frohlich, Emily S. Kappenman, Kelvin O. Lim, Colleen Loo, Antonio Mantovani, David P. McMullen, Lucas C. Parra, Michele Pearson, Jessica D. Richardson, Judith M. Rumsey, Pejman Sehatpour, David Sommers, Gozde Unal, Eric M. Wassermann, Adam J. Woods, Sarah H. Lisanby

Abstract

Background

Neuropsychiatric disorders are a leading source of disability and require novel treatments that target mechanisms of disease. As such disorders are thought to result from aberrant neuronal circuit activity, neuromodulation approaches are of increasing interest given their potential for manipulating circuits directly. Low intensity transcranial electrical stimulation (tES) with direct currents (transcranial direct current stimulation, tDCS) or alternating currents (transcranial alternating current stimulation, tACS) represent novel, safe, well-tolerated, and relatively inexpensive putative treatment modalities.

Objective

This report seeks to promote the science, technology and effective clinical applications of these modalities, identify research challenges, and suggest approaches for addressing these needs in order to achieve rigorous, reproducible findings that can advance clinical treatment.

Methods

The National Institute of Mental Health (NIMH) convened a workshop in September 2016 that brought together experts in basic and human neuroscience, electrical stimulation biophysics and devices, and clinical trial methods to examine the physiological mechanisms underlying tDCS/tACS, technologies and technical strategies for optimizing stimulation protocols, and the state of the science with respect to therapeutic applications and trial designs.

Results

Advances in understanding mechanisms, methodological and technological improvements (e.g., electronics, computational models to facilitate proper dosing), and improved clinical trial designs are poised to advance rigorous, reproducible therapeutic applications of these techniques. A number of challenges were identified and meeting participants made recommendations made to address them.

Conclusions

These recommendations align with requirements in NIMH funding opportunity announcements to, among other needs, define dosimetry, demonstrate dose/response relationships, implement rigorous blinded trial designs, employ computational modeling, and demonstrate target engagement when testing stimulation-based interventions for the treatment of mental disorders.

Esmaeilpour Z, Milosevic M, Azevedo K, Khadka N, Navarro J, Brunoni A, Popovic MR, Bikson M, Fonoff ET

---

Download: PDF published in Brain Stimulation  DOI

Abstract

During transcranial direct current stimulation (tDCS) weak (1-2 mA) currents are applied across the head, producing low-intensity electric fields in the brain with the intention of modulating neuronal function. For any application of tDCS spanning cognitive neuroscience and neuropsychiatric therapies [1], understanding the amount of current delivered to the brain and the resulting electric field (in V/m) produced is thus important. In animal studies, direct current (DC) electric fields as low as 0.2-1.0 V/m influence neuronal excitability and plasticity [2, 3]. Since measurement of electric field in human is difficult to implement, high-resolution finite element head models [4] have been used to predict brain current flow during tDCS [5] – with many reports adapting a standard (S#) head [6-8]. There have been previous attempts to validate computational model predictions indirectly with scalp electrodes [9] and neurophysiology [10] during tDCS, as well as directly using intra-cranial electrodes, but not with DC stimulation [11, 12]. In this pilot study, DC voltage was measured using deep brain stimulation (DBS) and epidural lead electrodes during application of tDCS in human subjects. The results were evaluated against a standard (S#) head model. The model predictions of voltage produced across cortical (epidural) electrodes were consistent with recorded data, while subcortical (DBS) voltages were sensitive to conductivity assigned to subcortical structures.

N. Zareen , M. Shinozaki , D. Ryan , H. Alexander , A. Amer, D.Q. Truong, N. Khadka, A. Sarkar, S. Naeem, M. Bikson , J.H. Martin

---

Download: PDF published in  Experimental Neurology DOI

Abstract

Cervical injuries are the most common form of SCI. In this study, we used a neuromodulatory approach to promote skilled movement recovery and repair of the corticospinal tract (CST) after a moderately severe C4 midline contusion in adult rats. We used bilateral epidural intermittent theta burst (iTBS) electrical stimulation of motor cortex to promote CST axonal sprouting and cathodal trans-spinal direct current stimulation (tsDCS) to enhance spinal cord activation to motor cortex stimulation after injury. We used Finite Element Method (FEM) modeling to direct tsDCS to the cervical enlargement. Combined iTBS-tsDCS was delivered for 30 min daily for 10 days. We compared the effect of stimulation on performance in the horizontal ladder and the Irvine Beattie and Bresnahan forepaw manipulation tasks and CST axonal sprouting in injury-only and injury + stimulation animals. The contusion eliminated the dorsal CST in all animals. tsDCS significantly enhanced motor cortex evoked responses after C4 injury. Using this combined spinal-M1 neuromodulatory approach, we found significant recovery of skilled locomotion and forepaw manipulation skills compared with injury-only controls. The spared CST axons caudal to the lesion in both animal groups derived mostly from lateral CST axons that populated the contralateral intermediate zone. Stimulation enhanced injury-dependent CST axonal outgrowth below and above the level of the injury. This dual neuromodulatory approach produced partial recovery of skilled motor behaviors that normally require integration of posture, upper limb sensory information, and intent for performance. We propose that the motor systems use these new CST projections to control movements better after injury.

New Paper: Incomplete evidence that increasing current intensity of tDCS boosts outcomes

Download: PDF published in Brain Stimulation – doi.org/10.1016/j.brs.2017.12.002

Zeinab Esmaeilpour, Paola Marangolo, Benjamin M. Hampstead, Sven Bestmann, Elisabeth Galletta, Helena Knotkova, Marom Bikson

ABSTRACT
Background: Transcranial direct current stimulation (tDCS) is investigated to modulate neuronal function by applying a fixed low-intensity direct current to scalp.

Objectives: We critically discuss evidence for a monotonic response in effect size with increasing current intensity, with a specific focus on a question if increasing applied current enhance the efficacy of tDCS.

Methods: We analyzed tDCS intensity does-response from different perspectives including biophysical modeling, animal modeling, human neurophysiology, neuroimaging and behavioral/clinical measures. Further, we discuss approaches to design dose-response trials.

Results: Physical models predict electric field in the brain increases with applied tDCS intensity. Data from animal studies are lacking since a range of relevant low-intensities is rarely tested. Results from imaging studies are ambiguous while human neurophysiology, including using transcranial magnetic stimulation (TMS) as a probe, suggests a complex state-dependent non-monotonic dose response. The diffusivity of brain current flow produced by conventional tDCS montages complicates this analysis, with relatively few studies on focal High Definition (HD)-tDCS. In behavioral and clinical trials, only a limited range of intensities (1-2 mA), and typically just one intensity, are conventionally tested; moreover, outcomes are subject brain-state dependent. Measurements and models of current flow show that for the same applied current, substantial differences in brain current occur across individuals. Trials are thus subject to inter-individual differences that complicate consideration of population-level dose response.

Conclusion: The presence or absence of simple dose response does not impact how efficacious a given tDCS dose is for a given indication. Understanding dose-response in human applications of tDCS is needed for protocol optimization including individualized dose to reduce outcome variability, which requires intelligent design of dose-response studies.

A Short Practicum on Deep Learning for EEG-based Brain Computer Interfaces
Presented by Vernon Lawhern of the Army Research Laboratory
Location: CDI 1.352 (First floor conference room)
Date and Time: Thursday, November 30, 2017 from 11am to 2pm
Lunch will be provided! Bring a laptop with Python Installed

Vernon will be available on Thursday afternoon and Friday morning for those who would like to try and obtain feedback on methods outlined in the workshop

See flyer below on how to RSVP and for more information

Dr. Marom Bikson interviewed by US News and World Report for a feature on

Can Transcranial Stimulation Help With Depression?

“Brain zapping”  helps patients who don’t respond to other treatments.

Read it link

“Bikson sees great strides being made in the coming years. “We are at baby aspirin levels of dosage and flip-phone levels of technology,” he says. “We have not even scratched the surface. We haven’t seen anything yet in the potential of electroceuticals.”

New Paper: High-Definition transcranial direct current stimulation in early onset epileptic encephalopathy: a case study

Download: PDF published in Brain Injury doi.org/10.1080/02699052.2017.1390254

Oded Meiron, Rena Gale, Julia Namestnic, Odeya Bennet-Back, Jonathan Davia, Nigel Gebodh, Devin Adair, Zeinab Esmaeilpour, and Marom Bikson

ABSTRACT

Primary objective: Early onset epileptic encephalopathy is characterized by high daily seizure-frequency, multifocal epileptic discharges, severe psychomotor retardation, and death at infancy. Currently, there are no effective treatments to alleviate seizure frequency and high-voltage epileptic discharges in these catastrophic epilepsy cases. The current study examined the safety and feasibility of High-Definition transcranial direct current stimulation (HD-tDCS) in reducing epileptiform activity in a 30-month-old child suffering from early onset epileptic encephalopathy.

Design and Methods: HD-tDCS was administered over 10 intervention days spanning two weeks including pre- and post-intervention video-EEG monitoring. Results: There were no serious adverse events or side effects related to the HD-tDCS intervention. Frequency of clinical seizures was not significantly reduced. However, interictal sharp wave amplitudes were significantly lower during the post-intervention period versus baseline. Vital signs and blood biochemistry remained stable throughout the entire study.

Conclusions: These exploratory findings support the safety and feasibility of 4 × 1 HD-tDCS in early onset epileptic encephalopathy and provide the first evidence of HD-tDCS effects on paroxysmal EEG features in electroclinical cases under the age of 36 months. Extending HD-tDCS treatment may enhance electrographic findings and clinical effects.

Event Time and Location: Thursday 11/16 at noon in CDI 3.352

Zeinab Esmaeilpour will present her work on brain stimulation and fMRI

tDCS integration with functional magnetic resonance imaging (fMRI)

Abstract:

Transcranial direct current stimulation (tDCS) is a non-invasive stimulation method that provides clinicians and researchers a tool to modulate central nervous system excitability in human and thereby contribute to exploration of brain-behavior relationship and develop treatment for various neurological and psychiatric disorders. However, despite its obvious promise, the potential of tDCS cannot be fully exploited as there is still a lack of understanding of the neural mechanisms underpinning stimulation. A key methodological advance toward bridging the gap in our understanding of the neural mechanisms of tDCS effects involves integration of tDCS with modern clinical and cognitive neuroscience techniques.

Magnetic resonance imaging (MRI) provides a high degree of spatial resolution regarding both brain structure and function, with the ability to assess brain-behavior questions across the entire brain. Thus, integration of tDCS with functional MRI provides the ability to evaluate not only correlations between brain function and behavior, but also experimentally manipulate brain activity in stimulated brain regions and assess how these observational relationships between the brain and behavior change. Thus, integration of tDCS with functional MRI has the potential to provide greater causal insight into the brain-behavior relationship in contrast to observational studies using these methods in isolation.

However, in recent years, there has been an increasing interest in using advanced neuroimaging techniques to study the effects of tDCS – both in healthy controls and clinical populations. Once technical difficulties are overcome, the combination of tDCS with functional MRI provides a powerful tool that allows us to study not only brain regions directly stimulated by tDCS, but also how tDCS modulates activity in the rest of the brain. In the literature of tDCS-fMRI, this combination could be categorized into three different groups: Hypothesis testing, outcome measure and response prediction.

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.