Download: PDF published in Scientific Reports – DOI

Limary M. Cancel, Katherin Arias, Marom Bikson, and John M. Tarbell

We investigated the effects of direct current stimulation (DCS) on fluid and solute transport across endothelial cell (EC) monolayers in vitro. Our motivation was transcranial direct current  stimulation (tDCS) that has been investigated for treatment of neuropsychiatric disorders, to enhance neurorehabilitation, and to change cognition in healthy subjects. The mechanisms underlying this diversity of applications remain under investigation. To address the possible role of blood-brain barrier (BBB) changes during tDCS, we applied direct current to cultured EC monolayers in a specially designed chamber that generated spatially uniform direct current. DCS induced fluid and solute movement across EC layers that persisted only for the duration of the stimulation suggesting an electroosmosis mechanism. The direction of induced transport reversed with DCS polarity – a hallmark of the electroosmotic effect. The magnitude of DCS-induced flow was linearly correlated to the magnitude of the applied current. A mathematical model based on a two-pore description of the endothelial transport barrier and a Helmholtz model of the electrical double layer describes the experimental data accurately and predicts enhanced significance of this mechanism in less permeable monolayers. This study demonstrates that DCS transiently alters the transport function of the BBB suggesting a new adjunct mechanism of tDCS.

Download: PDF published in Frontiers in Behavioral Neuroscience – DOI

Alexa Riggs, Vaishali Patel, Bhaskar Paneri, Russell K. Portenoy, Marom Bikson and Helena Knotkova

Transcranial direct current stimulation (tDCS) delivered in multiple sessions can reduce symptom burden, but access of chronically ill patients to tDCS studies is constrained by the burden of office-based tDCS administration. Expanded access to this therapy can be accomplished through the development of interventions that allow at-home tDCS applications.

Objective: We describe the development and initial feasibility assessment of a novel intervention for the chronically ill that combines at-home tDCS with telehealth support.

Methods: In the developmental phase, the tDCS procedure was adjusted for easy application by patients or their informal caregivers at home, and a tDCS protocol with specific elements for enhanced safety and remote adherence monitoring was created. Lay language instructional materials were written and revised based on expert feedback. The materials were loaded onto a tablet allowing for secure video-conferencing. The telehealth tablet was paired with an at-home tDCS device that allowed for remote dose control via electronic codes dispensed to patients prior to each session. tDCS was delivered in two phases: once daily on 10 consecutive days, followed by an as needed regimen for 20 days. Initial feasibility of this tDCS-telehealth system was evaluated in four patients with advanced chronic illness and multiple symptoms. Change in symptom burden and patient satisfaction were assessed with the Condensed Memorial Symptom Assessment Scale (CMSAS) and a tDCS user survey.

Results: The telehealth-tDCS protocol includes one home visit and has seven patient-tailored elements and six elements enhancing safety monitoring. Replicable electrode placement at home without 10–20 EEG measurement is achieved via a headband that holds electrodes in a pre-determined position. There were no difficulties with patients’ training, protocol adherence, or tolerability. A total of 60 tDCS sessions were applied. No session required discontinuation, and there were no adverse events. Data collection was feasible and there were no missing data. Satisfaction with the tDCS-telehealth procedure was high and the patients were comfortable using the system.

Conclusion: At-home tDCS with telehealth support appears to be a feasible approach for the management of symptom burden in patients with chronic illness. Further studies to evaluate and optimize the protocol effectiveness for symptom-control outcomes are warranted.

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

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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

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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

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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.