Argyelan M, Oltedal L, Deng Z-D, Wade B, Bikson M, Joanlanne A, Sanghani S, Bartsch H, Cano M, Dale AM, Dannlowski U, Dols A, Enneking V, Espinoza R, Kessler U, Narr KL, Oedegaard KJ, Oudega ML, Redlich R, Stek ML, Takamiya A, Emsell L, Bouckaert F, Sienaert P, Pujol J, Tendolkar I, van Eijndhoven P, Petrides G, Malhotra AK, Abbott C. Electric field causes volumetric changes in the human brain. eLife. 2019 Oct 23;8. Available from: http://dx.doi.org/10.7554/eLife.49115

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Abstract

Recent longitudinal neuroimaging studies in patients with electroconvulsive therapy (ECT) suggest local effects of electric stimulation (lateralized) occur in tandem with global seizure activity (generalized). We used electric field (EF) modeling in 151 ECT treated patients with depression to determine the regional relationships between EF, unbiased longitudinal volume change, and antidepressant response across 85 brain regions. The majority of regional volumes increased significantly, and volumetric changes correlated with regional electric field (t = 3.77, df = 83, r = 0.38, p=0.0003). After controlling for nuisance variables (age, treatment number, and study site), we identified two regions (left amygdala and left hippocampus) with a strong relationship between EF and volume change (FDR corrected p<0.01). However, neither structural volume changes nor electric field was associated with antidepressant response. In summary, we showed that high electrical fields are strongly associated with robust volume changes in a dose-dependent fashion.

Prof. Marom Bikson interviewed for Behind the Bench. Includes discussion of how the the Bikson’s lab unique approach to neural engineering and medical device creation.

“There was not much work at CWRU in non-invasive stimulation. By picking that area for my research I had to leverage a lot of the tools that were developed at Case, but I also had to adapt them and create a new sort of toolkit of neural engineering for non-invasive electrical stimulation,” Bikson said. “I’m starting to work more and more with them,” he continued. “For example, I’m working with Rafael Carbunaru, who was a student of Dominique’s and now he’s directing R&D at Boston Scientific. And the reason these things came full circle is because all of a sudden, the fields of invasive and non-invasive neuromodulation that were seemingly different started to push in against each other. All of a sudden, high frequency became relevant for non-invasive and all of a sudden, sub-threshold became relevant for invasive. And oscillations became relevant for everything. Closed loop became relevant for everything. And in this way, I’m starting to work more in spinal cord stimulation, but I’m doing it with toolkits that we developed for non-invasive neuromodulation. Another example is individualized modeling was pioneered first for invasive but was pushed ahead for non-invasive. A lot of those tools can now be applied back to invasive.”

Read the full article: https://www.neurotechbench.com/post/marom-bikson-is-making-an-impact

Kronberg G, Rahman A, Sharma M, Bikson M, Parra LC. Direct current stimulation boosts hebbian plasticity in vitro. Brain Stimulation. 2019 Oct; Available from: http://dx.doi.org/10.1016/j.brs.2019.10.014

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Abstract

There is evidence that transcranial direct current stimulation (tDCS) can improve learning performance. Arguably, this effect is related to long term potentiation (LTP), but the precise biophysical mechanisms remain unknown. We propose that direct current stimulation (DCS) causes small changes in postsynaptic membrane potential during ongoing endogenous synaptic activity. The altered voltage dynamics in the postsynaptic neuron then modify synaptic strength via the machinery of endogenous voltage-dependent Hebbian plasticity. This hypothesis predicts that DCS should exhibit Hebbian properties, namely pathway specificity and associativity. We studied the effects of DCS applied during the induction of LTP in the CA1 region of rat hippocampal slices and using a biophysical computational model. DCS enhanced LTP, but only at synapses that were undergoing plasticity, confirming that DCS respects Hebbian pathway specificity. When different synaptic pathways cooperated to produce LTP, DCS enhanced this cooperation, boosting Hebbian associativity. Further slice experiments and computer simulations support a model where polarization of postsynaptic pyramidal neurons drives these plasticity effects through endogenous Hebbian mechanisms. The model is able to reconcile several experimental results by capturing the complex interaction between the induced electric field, neuron morphology, and endogenous neural activity. These results suggest that tDCS can enhance associative learning. We propose that clinical tDCS should be applied during tasks that induce Hebbian plasticity to harness this phenomenon, and that the effects should be task specific through their interaction with endogenous plasticity mechanisms. Models that incorporate brain state and plasticity mechanisms may help to improve prediction of tDCS outcomes.

Khadka N, Truong DQ, Williams P, Martin JH, Bikson M. The Quasi-uniform assumption for Spinal Cord Stimulation translational research. Journal of Neuroscience Methods. 201. ;328:108446. http://dx.doi.org/10.1016/j.jneumeth.2019.108446

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Download PDF published in Journal Neuroscience Methods— DOI

Abstract

Background: Quasi-uniform assumption is a general theory that postulates local electric field predicts neuronal activation. Computational current flow model of spinal cord stimulation (SCS) of humans and animal models inform how the quasi-uniform assumption can support scaling neuromodulation dose between humans and translational animal.

New method: Here we developed finite element models of cat and rat SCS, and brain slice, alongside SCS models. Boundary conditions related to species specific electrode dimensions applied, and electric fields per unit current (mA) predicted.

Results: Clinically and across animal, electric fields change abruptly over small distance compared to the neuronal morphology, such that each neuron is exposed to multiple electric fields. Per unit current, electric fields generally decrease with body mass, but not necessarily and proportionally across tissues. Peak electric field in dorsal column rat and cat were ∼17x and ∼1x of clinical values, for scaled electrodes and equal current. Within the spinal cord, the electric field for rat, cat, and human decreased to 50% of peak value caudo-rostrally (C5–C6) at 0.48 mm, 3.2 mm, and 8 mm, and mediolaterally at 0.14 mm, 2.3 mm, and 3.1 mm. Because these space constants are different, electric field across species cannot be matched without selecting a region of interest (ROI)

Comparison of existing method: This is the first computational model to support scaling neuromodulation dose between humans and translational animal.

Conclusions: Inter-species reproduction of the electric field profile across the entire surface of neuron populations is intractable. Approximating quasi-uniform electric field in a ROI is a rational step to translational scaling.

1. Can kilohertz-frequency Deep Brain Stimulation increase brain tissue temperature?

   Niranjan Khadka, Irene Harmsen, Andres M. Lozano, Marom Bikson

2. Waveform Characterization, IPG battery life, and Temperature Increases by Senza HF10 Spinal Cord Stimulation System

   Adantachede L Zannou, Niranjan Khadka, Mohmad FallahRad, Dennis Q. Truong, Brian H Kopell, Marom Bikson

3. Modulation of Sleepiness and Physiology with Brain-Derived and Narrow-Band tACS

   Nigel Gebodh, Laura Vacchi, Zeinab Esmaeilpour, Devin Adair, Alexander Poltorak, Valeria Poltorak, Marom Bikson

4. Realistic Anatomically Detailed Open-source Spinal Cord Stimulation (RADO SCS) Model

   Niranjan Khadka, Xijie Liu, Jaiti Swami, Hans Zander, Evan Rogers, Scott Lempka, Marom Bikson

   Download: PDF

5. Mechanism of Temporal Interference (TI) stimulation

   Zeinab Esmaeilpour, Greg Kronberg, Lucas Parra, Marom Bikson

And Prof. Marom Bikson chairs and presents at Session 1: Session 1: New Engineering of Neuromodulation & Brain Machine Interfaces on “Personalized Neuromodulation: Reading the Brain to Write the Brain.” Download Slide: PDF

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Bahr Hosseini M, Hou J, Bikson M, Iacoboni M, Gornbein J, Saver JL. Central Nervous System Electrical Stimulation for Neuroprotection in Acute Cerebral Ischemia. Stroke. 2019 Oct;50(10):2892–901. https://doi.org/10.1161/STROKEAHA.119.025364.

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Download PDF published in Stroke — DOI

Abstract

Brain electrical stimulation, widely studied to facilitate recovery from stroke, has also been reported to confer direct neuroprotection in preclinical models of acute cerebral ischemia. Systematic review of controlled preclinical acute cerebral ischemia studies would aid in planning for initial human clinical trials. A systematic Medline search identified controlled, preclinical studies of central nervous system electrical stimulation in acute cerebral ischemia. Studies were categorized among 6 stimulation strategies. Three strategies applied different stimulation types to tissues within the ischemic zone (cathodal hemispheric stimulation [CHS], anodal hemispheric stimulation, and pulsed hemispheric stimulation), and 3 strategies applied deep brain stimulation to different neuronal targets remote from the ischemic zone (fastigial nucleus stimulation, subthalamic vasodilator area stimulation, and dorsal periaqueductal gray stimulation). Random-effects meta-analysis assessed electrical stimulation modification of final infarct volume. Study-level risk of bias and intervention-level readiness-for-translation were assessed using formal rating scales. Systematic search identified 28 experiments in 21 studies, including a total of 350 animals, of electrical stimulation in preclinical acute cerebral ischemia. Overall, in animals undergoing electrical stimulation, final infarct volumes were reduced by 37% (95% CI, 34%–40%; P<0.001), compared with control. There was evidence of heterogeneity of efficacy among stimulation strategies (I2=93.1%, P_heterogeneity<0.001). Among the within-ischemic zone stimulation strategies, only CHS significantly reduced the infarct volume (27 %; 95% CI, 22%–33%; P<0.001); among the remote-from ischemic zone approaches, all (fastigial nucleus stimulation, subthalamic vasodilator area stimulation, and dorsal periaqueductal gray stimulation) reduced infarct volumes by approximately half. On formal rating scales, CHS studies had the lowest risk of bias, and CHS had the highest overall quality of intervention-level evidence supporting readiness to proceed to clinical testing. Electrical stimulation reduces final infarct volume across preclinical studies. CHS shows the most robust evidence and is potentially appropriate for progression to early-stage human clinical trial testing as a promising neuroprotective intervention.

Niranjan Khadka, Helen Borges, Bhaskar Paneri, Trynia Kaufman, Electra Nassis, Adantchede L. Zannou, Yungjae Shin, Hyeongseob Choi, Seonghoon Kim, Kiwon Lee, Marom Bikson. Adaptive current tDCS up to 4 mA. Brain Stimulation. 2019 Jan;13(1):69–79. https://doi.org/10.1016/j.brs.2019.07.027

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Download: PDF published in Brain Stimulation — DOI

Abstract

Background: Higher tDCS current may putatively enhance efficacy, with tolerability the perceived limiting factor.

Objective: We designed and validated electrodes and an adaptive controller to provide tDCS up to 4 mA,while managing tolerability. The adaptive 4 mA controller included incremental ramp up, impedance-based current limits, and a Relax-mode where current is transiently decreased. Relax-mode was automatically activated by self-report VAS-pain score>5 and in some conditions by a Relax-button available to participants.

Methods: In a parallel-group participant-blind design with 50 healthy subjects, we used specialized electrodes to administer 3 daily session of tDCS for 11 min, with a lexical decision task as a distractor, in 5 study conditions: adaptive 4 mA, adaptive 4 mA with Relax-button, adaptive 4 mA with historical-Relax-button, 2 mA, and sham. A tablet-based stimulator with a participant interface regularly queried VAS pain score and also limited current based on impedance and tolerability. An Abort-button provided in all conditions stopped stimulation. In the adaptive 4 mA with Relax-button and adaptive 4 mA with historical-Relax-button conditions, participants could trigger a Relax-mode ad libitum, in the latter case with incrementally longer current reductions. Primary outcome was the average current delivered during each session, VAS pain score, and adverse event questionnaires. Current delivered was analyzed either excluding or including dropouts who activated Abort (scored as 0 current).

Results: There were two dropouts each in the adaptive 4 mA and sham conditions. Resistance based current attenuation was rarely activated, with few automatic VAS pain score triggered relax-modes. In conditions with Relax-button option, there were significant activation often irrespective of VAS pain score. Including dropouts, current across conditions were significantly different from each other with maximum current delivered during adaptive 4 mA with Relax-button. Excluding dropouts, maximum current was delivered with adaptive 4 mA. VAS pain score and adverse events for the sham was only significantly lower than the adaptive 4 mA with Relax-button and adaptive 4 mA with historical-Relax-button. There was no difference in VAS pain score or adverse events between 2 mA and adaptive 4 mA.

Conclusions: Provided specific electrodes and controllers, adaptive 4 mA tDCS is tolerated and effectively blinded, with acceptability likely higher in a clinical population and absence of regular querying. Indeed,presenting participants with overt controls increases rumination on sensation.

Prof. Marom Bikson discusses both home-based tDCS and HD-tDCS in IEEE “How a Tiny Electrical Current to the Brain Is Treating Medical Symptoms”.

Read the article: PDF

“Bikson, professor of biomedical engineering at City University of New York (CUNY). He is also cofounder of Soterix Medical of New York City, which is developing tDCS for home, clinical, and research applications. On the medical-supervision side, Soterix is working on an automated home system that a clinician (or researcher if it’s part of a research project) can monitor and direct via telemedicine (Figure 4). “There’s a lot of technology that goes into that, including reliable communication between the technology and the site that’s providing the telemedicine, as well as automated software that can collect information from the patient on a daily basis, and can also deliver the prescription that the doctor sets,” Bikson said. “Although the software doesn’t decide what the treatment will be, it can withhold treatment until the patient is ready to receive it based on the doctor’s prescription schedule.”

“Going high-def: Besides the home-based tDCS system, Soterix also developed something quite different for use in research labs and clinics: targeted tDCS that delivers current to precise, small areas of the brain, as compared to the 5x5-cm areas covered by each of the two pads or sponges seen in typical home based systems, Bikson explained. The idea with targeted tDCS is to personalize treatment for individual patients and/or to reduce distinct symptoms. Soterix actually engineered the first noninvasive, targeted, and low-intensity neuromodulation technology, dubbed high-definition tDCS (HD-tDCS), back in 2009. “HD-tDCS and its variants, which include HD-tACS, use an array of smaller electrodes to stimulate specific parts of the brain,”

Bikson M, Esmaeilpour Z, Adair D, Kronberg G, Tyler WJ, Antal A, Datta A, Sabel BA, Nitsche MA, Loo C, Edwards D, Ekhtiari H, Knotkova H, Woods AJ, Hampstead BM, Badran BW, Peterchev AV. (2019). Transcranial electrical stimulation nomenclature. Brain Stimulation. https://doi.org/10.1016/j.brs.2019.07.010 PDF

Download: PDF published in Brain Stimulation – DOI

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Abstract

Transcranial electrical stimulation (tES) aims to alter brain function non-invasively by applying current to electrodes on the scalp. Decades of research and technological advancement are associated with a growing diversity of tES methods and the associated nomenclature for describing these methods. Whether intended to produce a specific response so the brain can be studied or lead to a more enduring change in behavior (e.g. for treatment), the motivations for using tES have themselves influenced the evolution of nomenclature, leading to some scientific, clinical, and public confusion. This ambiguity arises from (i) the infinite parameter space available in designing tES methods of application and (ii) varied naming conventions based upon the intended effects and/or methods of application. Here, we compile a cohesive nomenclature for contemporary tES technologies that respects existing and historical norms, while incorporating insight and classifications based on state-of-the-art findings. We consolidate and clarify existing terminology conventions, but do not aim to create new nomenclature. The presented nomenclature aims to balance adopting broad definitions that encourage flexibility and innovation in research approaches, against classification specificity that minimizes ambiguity about protocols but can hinder progress. Constructive research around tES classification, such as transcranial direct current stimulation (tDCS), should allow some variations in protocol but also distinguish from approaches that bear so little resemblance that their safety and efficacy should not be compared directly. The proposed framework includes terms in contemporary use across peer-reviewed publications, including relatively new nomenclature introduced in the past decade, such as transcranial alternating current stimulation (tACS) and transcranial pulsed current stimulation (tPCS), as well as terms with long historical use such as electroconvulsive therapy (ECT). We also define commonly used terms-of-the-trade including electrode, lead, anode, and cathode, whose prior use, in varied contexts, can also be a source of confusion. This comprehensive clarification of nomenclature and associated preliminary proposals for standardized terminology can support the development of consensus on efficacy, safety, and regulatory standards.

Computational Finite Element Method (FEM) forward modeling workflow for transcranial Direct Current Stimulation (tDCS) current flow on MRI-derived head: Simpleware and COMSOL Multiphysics tutorial. Ole Seibt, Dennis Truong, Niranjan Khadka, Yu Huang, Marom Bikson. bioRxiv 704940; doi: https://doi.org/10.1101/704940

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Abstract

Transcranial Direct Current Stimulation (tDCS) dose designs are often based on computational Finite Element Method (FEM) forward modeling studies. These FEM models educate researchers about the resulting current flow (intensity and pattern) and so the resulting neurophysiological and behavioral changes based on tDCS dose (mA), resistivity of head tissues (e.g. skin, skull, CSF, brain), and head anatomy. Moreover, model support optimization of montage to target specific brain regions. Computational models are thus an ancillary tool used to inform the design, set-up and programming of tDCS devices, and investigate the role of parameters such as electrode assembly, current directionality, and polarity of tDCS in optimizing therapeutic interventions. Computational FEM modeling pipeline of tDCS initiates with segmentation of an exemplary magnetic resonance imaging (MRI) scan of a template head into multiple tissue compartments to develop a higher resolution (< 1 mm) MRI derived FEM model using Simpleware ScanIP. Next, electrode assembly (anode and cathode of variant dimension) is positioned over the brain target and meshed at different mesh densities. Finally, a volumetric mesh of the head with electrodes is imported in COMSOL and a quasistatic approximation (stead-state solution method) is implemented with boundary conditions such as inward normal current density (anode), ground (cathode), and electrically insulating remaining boundaries. A successfully solved FEM model is used to visualize the model prediction via different plots (streamlines, volume plot, arrow plot).

Valero-Cabré A, Sanches C, Godard J, Fracchia O, Dubois B, Levy R, Truong DQ, Bikson M, Teichmann M. (2019). Language boosting by transcranial stimulation in progressive supranuclear palsy. Neurology, 10.1212/WNL.0000000000007893. https://doi.org/10.1212/wnl.0000000000007893. PDF

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Download: PDF published in Neurology – DOI

Abstract

[Our objective was t]o explore whether transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) can improve language capacities in patients with progressive supranuclear palsy (PSP). We used a sham-controlled double-blind crossover design to assess the efficiency of tDCS over the DLPFC in a cohort of 12 patients with PSP. In 3 separate sessions, we evaluated the ability to boost the left DLPFC via left-anodal (excitatory) and right-cathodal (inhibitory) tDCS, while comparing them to sham tDCS. Tasks assessing lexical access (letter fluency task) and semantic access (category judgment task) were applied immediately before and after the tDCS sessions to provide a marker of potential language modulation. The comparison with healthy controls showed that patients with PSP were impaired on both tasks at baseline. Contrasting poststimulation vs prestimulation performance across tDCS conditions revealed language improvement in the category judgment task following right-cathodal tDCS, and in the letter fluency task following left-anodal tDCS. A computational finite element model of current distribution corroborated the intended effect of left-anodal and right-cathodal tDCS on the targeted DLPFC. Our results demonstrate tDCS-driven language improvement in PSP. They provide proof-of-concept for the use of tDCS in PSP and set the stage for future multiday stimulation regimens, which might lead to longer-lasting therapeutic effects promoted by neuroplasticity. This study provides Class III evidence that for patients with PSP, tDCS over the DLPFC improves performance in some language tasks.

June 23-24, 2019 at the BioEM2019  The Bioelectromagnetics Society (BEMS) and the European BioElectromagnetics Association (EBEA) joint meeting in Montpellier, France

Prof. Marom Bikson instructs on “Theory and hands-on practical for tDCS and tACS” June 23, 2019 Details   slides :tdcs_tacs_2019_final-compressed

and gives plenary lecture on “Electrical Brain Stimulation” on June 24, 2019. Conference website  slides: BioEM_2019_Final_Bikson-compressed

Pictures from the event

Zannou AL, Khadka N, Truong D, FallahRad M, Kopell B, Bikson, M. Tissue Temperature Increases by a 10 kHz Spinal Cord Stimulation System: Phantom and Bioheat Model. Neuromodulation: Technology at the Neural Interface. https://doi.org/10.1111/ner.12980. 2019. PDF

Download: PDF published in Neuromodulation: Technology at the Neural Interface – DOI

Abstract

A recently introduced Spinal Cord Stimulation (SCS) system operates at 10 kHz, faster than conventional SCS systems, resulting in significantly more power delivered to tissues. Using a SCS heat phantom and bioheat multi‐physics model, we characterized tissue temperature increases by this 10 kHz system. We also evaluated its Implanted Pulse Generator (IPG) output compliance and the role of impedance in temperature increases. The 10 kHz SCS system output was characterized under resistive loads (1–10 KΩ). Separately, fiber optic temperature probes quantified temperature increases (ΔTs) around the SCS lead in specially developed heat phantoms. The role of stimulation Level (1–7; ideal pulse peak‐to‐peak of 1–7mA) was considered, specifically in the context of stimulation current Root Mean Square (RMS). Data from the heat phantom were verified with the SCS heat‐transfer models. A custom high‐bandwidth stimulator provided 10 kHz pulses and sinusoidal stimulation for control experiments. The 10 kHz SCS system delivers 10 kHz biphasic pulses (30‐20‐30 μs). Voltage compliance was 15.6V. Even below voltage compliance, IPG bandwidth attenuated pulse waveform, limiting applied RMS. Temperature increased supralinearly with stimulation Level in a manner predicted by applied RMS. ΔT increases with Level and impedance until stimulator compliance was reached. Therefore, IPG bandwidth and compliance dampen peak heating. Nonetheless, temperature increases predicted by bioheat multi‐physic models (ΔT = 0.64°C and 1.42°C respectively at Level 4 and 7 at the cervical segment; ΔT = 0.68°C and 1.72°C respectively at Level 4 and 7 at the thoracic spinal cord)–within ranges previously reported to effect neurophysiology. Heating of spinal tissues by this 10 kHz SCS system theoretically increases quickly with stimulation level and load impedance, while dampened by IPG pulse bandwidth and voltage compliance limitations. If validated in vivo as a mechanism of kHz SCS, bioheat models informed by IPG limitations allow prediction and optimization of temperature changes.

Im JJ, Jeong H, Bikson M, Woods AJ, Unal G, Oh JK, Na S, Park, J-S, Knotkova H, Song I-K, Chung Y-A. Effects of 6-month at-home transcranial direct current stimulation on cognition and cerebral glucose metabolism in Alzheimer’s disease. Brain Stimulation 12 (2019) 1222e1228. https://doi.org/10.1016/j.brs.2019.06.003.

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Download: PDF published in Brain Stimulation – DOI

Abstract

Although single or multiple sessions of transcranial direct current stimulation (tDCS) on the prefrontal cortex over a few weeks improved cognition in patients with Alzheimer’s disease (AD), effects of repeated tDCS over longer period and underlying neural correlates remain to be elucidated. This study investigated changes in cognitive performances and regional cerebral metabolic rate for glucose (rCMRglc) after administration of prefrontal tDCS over 6 months in early AD patients. Patients with early AD were randomized to receive either active (n = 11) or sham tDCS (n = 7) over the dorsolateral prefrontal cortex (DLPFC) at home every day for 6 months (anode F3/cathode F4, 2 mA for 30 min). All patients underwent neuropsychological tests and brain 18F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) scans at baseline and 6-month follow-up. Changes in cognitive performances and rCMRglc were compared between the two groups. Compared to sham tDCS, active tDCS improved global cognition measured with Mini-Mental State Examination (p for interaction = 0.02) and language function assessed by Boston Naming Test (p for interaction = 0.04), but not delayed recall performance. In addition, active tDCS prevented decreases in executive function at a marginal level (p for interaction < 0.10). rCMRglc in the left middle/inferior temporal gyrus was preserved in the active group, but decreased in the sham group (p for interaction < 0.001). Daily tDCS over the DLPFC for 6 months may improve or stabilize cognition and rCMRglc in AD patients, suggesting the therapeutic potential of repeated at-home tDCS.

Meiron O, Gale R, Namestnic J, Bennet-Back O, Gebodh N, Esmaeilpour Z, Mandzhiyev V and Bikson M (2019) Antiepileptic Effects of a Novel Non-invasive Neuromodulation Treatment in a Subject With Early-Onset Epileptic Encephalopathy: Case Report With 20 Sessions of HD-tDCS Intervention. Front. Neurosci. 13:547. doi: 10.3389/fnins.2019.00547 PDF

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Download: PDF published in Frontiers in Neuroscience – DOI

Abstract

The current clinical investigation examined high-definition transcranial direct current stimulation (HD-tDCS) as a focal, non-invasive, anti-epileptic treatment in a child with early-onset epileptic encephalopathy. We investigated the clinical impact of repetitive (20 daily sessions) cathode-centered 4 × 1 HD-tDCS (1 mA, 20 min, 4 mm ring radius) over the dominant seizure-generating cortical zone in a 40-month-old child suffering from a severe neonatal epileptic syndrome known as Ohtahara syndrome (OS). Seizures and epileptiform activity were monitored and quantified using video-EEG over multiple days of baseline, intervention, and post-intervention periods. Primary outcome measures were changes in seizure frequency and duration on the last day of intervention versus the last baseline day, preceding the intervention. In particular, we examined changes in tonic spasms, tonic-myoclonic seizures (TM-S), and myoclonic seizures from baseline to post-intervention. A trend in TM-S frequency was observed indicating a reduction of 73% in TM-S frequency, which was non-significant [t(4) = 2.05, p = 0.1], and denoted a clinically significant change. Myoclonic seizure (M-S) frequency was significantly reduced [t(4) = 3.83, p = 0.019] by 68.42%, compared to baseline, and indicated a significant clinical change as well. A 73% decrease in interictal epileptic discharges (IEDs) frequency was also observed immediately after the intervention period, compared to IED frequency at 3 days prior to intervention. Post-intervention seizure-related peak delta desynchronization was reduced by 57%. Our findings represent a case-specific significant clinical response, reduction in IED, and change in seizure-related delta activity following the application of HD-tDCS. The clinical outcomes, as noted in the current study, encourage the further investigation of this focal, non-invasive neuromodulation procedure in other severe electroclinical syndromes (e.g., West syndrome) and in larger pediatric populations diagnosed with early-onset epileptic encephalopathy.

Ambrose-Zaken GV, FallahRad M, Bernstein H, Wall Emerson R and Bikson M (2019) Wearable Cane and App System for Improving Mobility in Toddlers/Pre-schoolers With Visual Impairment. Front. Educ. 4:44. doi: 10.3389/feduc.2019.00044 PDF

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Download: PDF published in Frontiers in Education – DOI

Abstract

Children with congenital severe visual impairment and blindness (SVI&B) are at greater risk of developing delays in motor and other developmental domains. This report describes a series of experiments conducted to evaluate a novel wearable cane and mobile application system prototype. The wearable cane and application system was tested on ability to (a) provide hands-free autonomous arc able to detect obstacles, level, and surface changes; (b) integrate into indoor/outdoor activities of a specialized pre-school for learners with SVI&B; and (c) be adopted by families, professionals and learners with SVI&B as a safe mobility solution. Sixteen stakeholders and 34 children under five with SVI&B evaluated the prototype system. The project successfully created a hands-free wearable white cane that provided students with SVI&B under age five with next step warning when walking across a variety of terrain. Pre-school participants with SVI&B easily adopted the wearable cane into their activities with minimal to no prompting or instruction. The P20 prototype scored well across usability features, including maintaining consistent, hands-free, autonomous arc. The invention of a hands-free mobility tool was a significant outcome of this project. These data support that autonomous arc has the ability to provide developmentally appropriate safe mobility solution for toddlers with SVI&B.

Neurology Today feature on “A New Study Suggests Non-Invasive Brain Stimulation Can Improve Working Memory” where Dr. Robert M.G. Reinhart and colleagues used High-Definition transcranial Alternating Current Stimulation (HD-tACS) to boost memory in older adults (trial published in Nature). Prof. Marom Bikson quoted as:

“Rather than overriding the network, HD-tACS modulates it,” said Marom Bikson, PhD, a scientist in the department of biomedical engineering at the City College of New York. Dr. Bikson was not directly involved in the study in Nature Neuroscience, but he invented the high-definition stimulation used in the experiments.

Many researchers are using high-definition technology to study the brain,” explained Dr. Bikson. “In this study, the stimulation was designed to reverse the brain’s electrical deficits that they observed in some older adults. A more robust working memory was revived by rhythmically synchronizing brain circuits.”

“They used these tools in a very clever way,” he continued. “They are not claiming that they proved this treatment enhances memory. A lot more work needs to be done, but this study provides support for moving ahead with such clinical trials.”

Read the full article here

Dennis Truong, Biomedical Engineering doctoral student in Dr. Bikson’s lab will defend his dissertation titled “Translational Modeling of Non-Invasive Electrical Stimulation” on Monday. May 13, 2019 at 11am in the Center for Discovery & Innovation building, room 4.352 (4th floor conference room). All are welcome to attend the public portion.

Abstract
Seminal work in the early 2000’s demonstrated the effect of low amplitude non-invasive electrical stimulation in people using neurophysiological measures (motor evoked potentials, MEPs). Clinical applications of transcranial Direct Current Stimulation (tDCS) have since proliferated, though the mechanisms are not fully understood. Efforts to refine the technique to improve results are on-going as are mechanistic studies both in vivo and in vitro. Volume conduction models are being applied to these areas of research, especially in the design and analysis of clinical montages. However, additional research on the parameterization of models remains.
In this dissertation, Finite Element Method (FEM) models of current flow were developed for clinical applications. The first image-derived models of obese subjects were developed to assess the relative impact of fat delineation from skin. Body mass index and more broadly inter-individual differences were considered. The effect of incorporating the meninges was predicted from CAD-based (Computer Aided Design) models before being translated into image-derived head models as an “emulated” CSF conductivity. These predictions were tested in a recently validated database of head models. Multi-scale models of transcutaneous vagus nerve stimulation (tVNS) were developed by coupling image-derived volume conduction models with physiological compartment modeling. The impact of local tissue inhomogeneities on fiber activation were considered.

Title: Brain Oscillations: Next Therapeutic Frontier?

Speaker: Dr. Flavio Frohlich, Associate Professor, The University of North Carolina (UNC) School of Medicine

When: Tuesday, March 26, 2019 at 2 pm

Where: CCNY Center for Discovery and Innovation, 3rd floor seminar room (CDI 3.352)

Contact: Greg Kronberg (gregkronberg@gmail.com, 212-650-8876) for access to CDI building

Abstract:

Electrical activity in brain networks exhibits rhythmic structure. These brain oscillations are impaired in both neurological and psychiatric illnesses. Over the last few years, we have learned that such oscillatory dynamics are surprisingly susceptible to weak but smartly timed perturbations. In my talk, I will show how we draw from engineering, biology, and medicine to develop new therapeutic strategies that leverage this fundamental response property of neuronal networks. I will outline how the integration of target identification, target engagement, and target validation provides a framework for the rational design of brain stimulation paradigms that target and restore brain oscillations. By combining computational modeling, preclinical animal research, and human clinical trials, we are on a long but very exciting journey towards revolutionizing how we treat brain disorders. Join us for the journey!

FallahRad M, Zannou AL, Khadka N, Prescott SA, Ratte S, Zhang T, Esteller R, Hershey B, Bikson M. Topical Review: Electrophysiology equipment for reliable study of kHz electrical stimulation. The Journal of Physiology. PDF

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Download: PDF published in The Journal of Physiology- DOI

Abstract

Characterizing the cellular targets of kHz (1–10 kHz) electrical stimulation remains a pressing topic in neuromodulation because expanding interest in clinical application of kHz stimulation has surpassed mechanistic understanding. The presumed cellular targets of brain stimulation do not respond to kHz frequencies according to conventional electrophysiology theory. Specifically, the low‐pass characteristics of cell membranes are predicted to render kHz stimulation inert, especially given the use of limited‐duty‐cycle biphasic pulses. Precisely because kHz frequencies are considered supra‐physiological, conventional instruments designed for neurophysiological studies such as stimulators, amplifiers, and recording microelectrodes do not operate reliably at these high rates. Moreover, for pulsed waveforms, the signal frequency content is well above the pulse repetition rate. Thus, the very tools used to characterize the effects of kHz electrical stimulation may themselves be confounding factors. We illustrate custom equipment design that supports reliable electrophysiological recording during kHz‐rate stimulation. Given the increased importance of kHz stimulation in clinical domains and compelling possibilities that mechanisms of actions may reflect yet undiscovered neurophysiological phenomena, attention to suitable performance of electrophysiological equipment is pivotal.