image courtesy of Caputron.
Use of Computational Modeling to Inform tDCS Electrode Montages for the Promotion of Language Recovery in Post-stroke Aphasia.
Galletta EE, Cancelli A, Cottone C, Simonelli I, Tecchio F, Bikson M, Marangolo P.
Brain Stimul. 2015 Nov-Dec;8(6):1108-15. doi: 10.1016/j.brs.2015.06.018.
Shin D, Khadka N, Fan J, Bikson M, Fu B. 2016
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Download: PDF published in SPIE Medical Imaging– DOI
Abstract
Transcranial Direct Current Stimulation (tDCS) is a non-invasive electrical stimulation technique investigated for a broad range of medical and performance indications. Whereas prior studies have focused exclusively on direct neuron polarization, our hypothesis is that tDCS directly modulates endothelial cells leading to transient changes in blood-brain-barrier (BBB) permeability (P) that are highly meaningful for neuronal activity. For this, we developed state-of-the-art imaging and animal models to quantify P to various sized solutes after tDCS treatment. tDCS was administered using a constant current stimulator to deliver a 1mA current to the right frontal cortex of rat (approximately 2 mm posterior to bregma and 2 mm right to sagittal suture) to obtain similar physiological outcome as that in the human tDCS application studies. Sodium fluorescein (MW=376), or FITC-dextrans (20K and 70K), in 1% BSA mammalian Ringer was injected into the rat (SD, 250-300g) cerebral circulation via the ipsilateral carotid artery by a syringe pump at a constant rate of ~3 ml/min. To determine P, multiphoton microscopy with 800-850 nm wavelength laser was applied to take the images from the region of interest (ROI) with proper microvessels, which are 100-200 micron below the pia mater. It shows that the relative increase in P is about 8-fold for small solute, sodium fluorescein, ~35-fold for both intermediate sized (Dex-20k) and large (Dex-70k) solutes, 10 min after 20 min tDCS pretreatment. All of the increased permeability returns to the control after 20 min post treatment. The results confirmed our hypothesis.
Fall 2016 Seminar Series Fall 2016 Seminar Series Department of Biomedical Engineering Wednesday, Nov. 30 @ 3PM in Steinman Hall Rm 402
Patient-centric innovation intersection
Dr. Hugo Caicedo
Janssen-Johnson & Johnson Pharmaceutical R&D
Abstract: The current FDA-based roadmap to drug and product development as well as regulatory decision- making and labeling, is based on four Clinical outcome assessments (COAs): Patient-reported outcome (PRO) measures, Clinician-reported outcome (ClinRO) measures, Observer-reported outcome (ObsRO) measures, and Performance outcome (PerfO) measures. In general, COAs are used to determine whether or not a therapy has demonstrated a net clinical benefit in a disease or health condition, in other words COAs assess safety and efficacy of a therapy. Under these conditions, individuals are subjected to “adequate and well-controlled studies”. The gap, however, is that in real life patients, in their natural environments, are under neither adequate nor well-controlled conditions, which limits both our capacity to understand the patient experience and our ability to develop innovated & targeted healthcare solutions. Additionally, current highly homogeneous and randomized clinical trials (RCTs) do not shed light on patient adherence to those therapies; about 50% of the patients with chronic diseases do not comply with medication therapy. During my presentation, I will talk about how three paradigms (Real World Evidence (RWE), Digital Analytics and Design Thinking) can converge and form a model that I created, the “Patient-centric innovation intersection”, to enable actionable insights for the development of targeted healthcare solutions, with particular focus in Diabetes therapy adherence.
Biosketch: Dr. Hugo Caicedo is a scientist subject matter expert in microfluidics, biomedical engineering and consumer healthcare at Janssen-Johnson & Johnson Pharmaceutical R&D in the Philadelphia area. There, he conducts preclinical research on drug discovery as well as strategic design on healthcare innovation to translate relevant science and technology into high-value partnerships that enable differentiated healthcare solutions. Currently, he is also a scholar trainee at the Corporate Sustainability and Innovation program at Harvard University. Dr. Caicedo holds a B.S in Electronics Engineering from the Universidad del Valle (Cali-Colombia) and a Ph.D. in Biomedical Engineering from the University of Illinois at Chicago (UIC). He was the recipient of MIT, Bogazicy University, Antalya University (Turkey) and UniversitéPierre and Marie Curie (France) pre-doctoral fellowships as well as one Harvard-MIT/HST post-doctoral fellowship. Dr. Caicedo has multiple publications including several peer-reviewed papers, two book chapters and a provisional patent application. Additionally, he has been awarded more than 20 recognition awards including: 2011, Ph.D student, African Colombian of the year in academia; 2012, Mayor’s Civic Merit Medal of Cali given directly by the President of Colombia; 2012, Distinguished PhD Student speaker at the 3rd US-Turkey Advanced Study Institute on Global Healthcare Challenges; 2015, BMES4SUCCESS, highlighted by the US Biomedical Engineering Society, as one of three —and the only member from industry— successful earlier career members in biomedical engineering; and 2016 Honorable Speaker invitation at the Biotechnology World Convention in Sao Paulo, Brazil.
Textbook of Neuromodulation
Principles, Methods and Clinical Applications
Springer. ISBN: 978-1-4939-1407-4
Methods and Technologies for Low-Intensity Transcranial Electrical Stimulation: Waveforms, Terminology, and Historical Notes
Page 7-16. Berkan Guleyupoglu, Pedro Schestatsky, Felipe Fregni, Marom Bikson
PDF: 10-1007978-1-4939-1408-12
A Role of Computational Modeling in Customization of Transcranial Direct Current Stimulation for Susceptible Populations
Dennis Truong, Preet Minhas, Albert Mokrejs, Marom Bikson
Direct current stimulation over the anterior temporal areas boosts semantic processing in primary progressive aphasia.
Teichmann M, Lesoil C, Godard J, Vernet M, Bertrand A, Levy R, Dubois B, Lemoine L, Truong DQ, Bikson M, Kas A, Valero-Cabré A. Ann Neurol. 2016 Nov;80(5):693-707. doi: 10.1002/ana.24766.
Abstract: Objective: Noninvasive brain stimulation in primary progressive aphasia (PPA) is a promising approach. Yet, applied to single cases or insufficiently controlled small-cohort studies, it has not clarified its therapeutic value. We here address the effectiveness of transcranial direct current stimulation (tDCS) on the semantic PPA variant (sv-PPA), applying a rigorous study design to a large, homogeneous sv-PPA cohort. Methods: Using a double-blind, sham-controlled counterbalanced cross-over design, we applied three tDCS condi- tions targeting the temporal poles of 12 sv-PPA patients. Efficiency was assessed by a semantic matching task orthogonally manipulating “living”/”nonliving” categories and verbal/visual modalities. Conforming to predominantly left-lateralized damage in sv-PPA and accounts of interhemispheric inhibition, we applied left hemisphere anodal- excitatory and right hemisphere cathodal-inhibitory tDCS, compared to sham stimulation. Results: Prestimulation data, compared to 15 healthy controls, showed that patients had semantic disorders predomi- nating with living categories in the verbal modality. Stimulation selectively impacted these most impaired domains: Left- excitatory and right-inhibitory tDCS improved semantic accuracy in verbal modality, and right-inhibitory tDCS improved processing speed with living categories and accuracy and processing speed in the combined verbal 3 living condition. Interpretation: Our findings demonstrate the efficiency of tDCS in sv-PPA by generating highly specific intrasemantic effects. They provide “proof of concept” for future applications of tDCS in therapeutic multiday regimes, potentially driv- ing sustained improvement of semantic processing. Our data also support the hotly debated existence of a left temporal- pole network for verbal semantics selectively modulated through both left-excitatory and right-inhibitory brain stimulation.
Contemp Clin Trials. 2016 Nov;51:65-71. doi: 10.1016/j.cct.2016.10.002. Epub 2016 Oct 15.
Study design and methodology for a multicentre, randomised controlled trial of transcranial direct current stimulation as a treatment for unipolar and bipolar depression.
Alonzo A, Aaronson S, Bikson M, Husain M, Lisanby S, Martin D, McClintock SM, McDonald WM, O’Reardon J, Esmailpoor Z, Loo C.
Download PDF: 10-1016j-cct-2016-10-002
Abstract: Transcranial Direct Current Stimulation (tDCS) is a new, non-invasive neuromodulation approach for treating depression that has shown promising efficacy. The aim of this trial was to conduct the first international, multicentre randomised controlled trial of tDCS as a treatment for unipolar and bipolar depression. The study recruited 120 participants across 6 sites in the USA and Australia. Participants received active or sham tDCS (2.5mA, 20 sessions of 30min duration over 4weeks), followed by a 4-week open label active treatment phase and a 4-week taper phase. Mood and neuropsychological outcomes were assessed with the primary antidepressant outcome measure being the Montgomery-Asberg Depression Rating Scale (MADRS). A neuropsychological battery was administered to assess safety and examine cognitive effects. The study also investigated the possible influence of genetic polymorphisms on outcomes. The trial was triple-blinded. Participants, tDCS treaters and study raters were blinded to each participant’s tDCS group allocation in the sham-controlled phase. Specific aspects of tDCS administration, device operation and group allocation were designed to optimise the integrity of blinding. Outcome measures will be tested using a mixed effects repeated measures analysis with the primary factors being Time as a repeated measure, tDCS condition (sham or active) and Diagnosis (unipolar or bipolar). A restricted number of random and fixed factors will be included as required to account for extraneous differences. As a promising treatment, tDCS has excellent potential for translation into widespread clinical use, being cost effective, portable, easy to operate and well tolerated.
Using Soterix Medical 1×1 CT platform: link
New Paper: Tolerability of Repeated Application of Transcranial Electrical Stimulation with Limited Outputs to Healthy Subjects
tolerability_limited_output_paper
Brain Stimulation 2016 May 24. pii: S1935-861X(16)30104-8. doi: 10.1016/j.brs.2016.05.008. [Epub ahead of print]
Abstract: The safety and tolerability of limited output tES in clinical populations support a non-significant risk designation. The tolerability of long-term use in a healthy population had remained untested. We tested the tolerability and compliance of two tES waveforms, tDCS and modulated high frequency transcranial pulsed current stimulation (MHF-tPCS) compared to sham-tDCS, applied to healthy subjects for three to five days (17–20 minutes per day) per week for up to six weeks in a communal setting. MHF-tPCS consisted of asymmetric high-frequency pulses (7–11 kHz) having a peak amplitude of 10–20 mA peak, adjusted by subject, resulting in an average current of 5–7 mA. A total of 100 treatment blind healthy subjects were randomly assigned to one of three treatment groups: tDCS (n = 33), MHF-tPCS (n = 30), or sham-tDCS (n = 37). In order to test the role of waveform, electrode type and montage were fixed across tES and sham-tDCS arms: high-capacity self-adhering electrodes on the right lateral forehead and back of the neck. We conducted 1905 sessions (636 sham-tDCS, 623 tDCS, and 646 MHF-tPCS sessions) on study volunteers over a period of six weeks. Common adverse events were primarily restricted to influences upon the skin and included skin tingling, itching, and mild burning sensations. The incidence of these events in the active tES treatment arms (MHF-tPCS, tDCS) was equivalent or significantly lower than their incidence in the sham-tDCS treatment arm. Other adverse events had a rarity (<5% incidence) that could not be significantly distinguished across the treatment groups. Some subjects were withdrawn from the study due to atypical headache (sham-tDCS n = 2, tDCS n = 2, and MHF-tPCS n = 3), atypical discomfort (sham-tDCS n = 0, tDCS n = 1, and MHF-tPCS n = 1), or atypical skin irritation (sham-tDCS n = 2, tDCS n = 8, and MHF-tPCS n = 1). The rate of compliance, elected sessions completed, for the MHF-tPCS group was significantly greater than the sham-tDCS group’s compliance (p = 0.007). There were no serious adverse events in any treatment condition. We conclude that repeated application of limited output tES across extended periods, limited to the hardware, electrodes, and protocols tested here, is well tolerated in healthy subjects, as previously observed in clinical populations.
Special CCNY BME Seminar Oct 26, 2016 featuring two Neural Engineering Lab researchers.
3 PM in the CCNY BME conference room. Steinman Hall Room 402
Modulating synaptic plasticity with tDCS
Department of Biomedical Engineering, The City College of New York
Abstract: Synapses allow communication between neurons and guide the flow of information throughout the brain. Modification of synapses in response to experience, or synaptic plasticity, is thought to be a cellular mechanism for learning and memory. Noninvasive tools to alter synaptic plasticity are therefore highly desirable. Recently, transcranial direct current stimulation (tDCS), has received much attention as a such a tool. tDCS is the noninvasive application of weak DC electric current to the brain through electrodes on the scalp. In this talk I will discuss mechanisms by which tDCS may influence synaptic plasticity, and how this can inform tDCS protocols to improve learning and memory
Bio-sketch: Greg Kronberg is currently a PhD student in the Biomedical Engineering department at The City College of New York (CCNY), where he works under Lucas Parra. He received his BS in Biology from the University of Maryland and his MS in Biomedical Engineering from CCNY. His research focuses on the use of electrical brain stimulation to improve learning and memory.
Measurements and models of electric fields in the in vivo human brain during transcranial electric stimulation
Department of Biomedical Engineering, The City College of New York
Abstract: Transcranial electric stimulation aims to stimulate the brain by applying weak electrical currents at the scalp. However, the magnitude and spatial distribution of electric fields in the human brain are unknown. Here we measure electric potentials intracranially in ten patients and estimate electric fields across the entire brain by leveraging calibrated current-flow models. Electric field magnitudes at the cortical surface reach values of 0.4 V/m, which is at the lower limit of effectiveness in animal studies. When individual anatomy is taken into account, the predicted electric field magnitudes match the recorded values with r=0.77. Modeling white matter anisotropy and different skull compartments does not improve accuracy, but correct magnitude estimates require an adjustment of conductivity values used in the literature. This is the first study to validate and calibrate current-flow models with in vivo intracranial recordings in humans, providing a solid foundation for targeting and interpretation of clinical trials.
Biosketch: Yu (Andy) Huang received his Ph.D. from Department of Biomedical Engineering, City College of New York. His research focuses on neuroimaging, image segmentation and computational modeling of image data. He received his B.S. and M.S. from University of Electronic Science and Technology of China, both in Biomedical Engineering.
Nature Scientific Reports
In-vivo Imaging of Magnetic Fields Induced by Transcranial Direct Current Stimulation (tDCS) in Human Brain using MRI
Mayank V. Jog, Robert X. Smith, Kay Jann, Walter Dunn, Belen Lafon, Dennis Truong, Allan Wu, Lucas Parra, Marom Bikson & Danny J. J. Wang
Transcranial direct current stimulation (tDCS) is an emerging non-invasive neuromodulation technique that applies mA currents at the scalp to modulate cortical excitability. Here, we present a novel magnetic resonance imaging (MRI) technique, which detects magnetic elds induced by tDCS currents. This technique is based on Ampere’s law and exploits the linear relationship between direct current and induced magnetic elds. Following validation on a phantom with a known path of electric current and induced magnetic eld, the proposed MRI technique was applied to a human limb (to demonstrate in- vivo feasibility using simple biological tissue) and human heads (to demonstrate feasibility in standard tDCS applications). The results show that the proposed technique detects tDCS induced magnetic elds as small as a nanotesla at millimeter spatial resolution. Through measurements of magnetic elds linearly proportional to the applied tDCS current, our approach opens a new avenue for direct in-vivo visualization of tDCS target engagement.
Full PDF: srep34385
Our new review is published:
Jackson MP, Rahman A, Lafon B, Kronberg G, Ling D, Parra LC, Bikson M, Animal Models of transcranial Direct Current Stimulation: Methods and Mechanisms, Clinical Neurophysiology, doi:10.1016/j.clinph.2016.08.016
Full PDF here: animalmodelstdcs_2016
Abstract: The objective of this review is to summarize the contribution of animal research using direct current stimulation (DCS) to our understanding of the physiological effects of transcranial direct current stimulation (tDCS). We comprehensively address experimental methodology in animal studies, broadly classified as: 1) transcranial stimulation; 2) direct cortical stimulation in vivo and 3) in vitro models. In each case advantages and disadvantages for translational research are discussed including dose translation and the overarching “quasi-uniform” assumption, which underpins translational relevance in all animal models of tDCS. Terminology such as anode, cathode, inward current, outward current, current density, electric field, and uniform are defined. Though we put key animal experiments spanning decades in perspective, our goal is not simply an exhaustive cataloging of relevant animal studies, but rather to put them in context of ongoing efforts to improve tDCS. Cellular targets, including excitatory neuronal somas, dendrites, axons, interneurons, glial cells, and endothelial cells are considered. We emphasize neurons are always depolarized and hyperpolarized such that effects of DCS on neuronal excitability can only be evaluated within subcellular regions of the neuron. Findings from animal studies on the effects of DCS on plasticity (LTP/LTD) and network oscillations are reviewed extensively. Any endogenous phenomena dependent on membrane potential changes are, in theory, susceptible to modulation by DCS. The relevance of morphological changes (galvanotropy) to tDCS is also considered, as we suggest microscopic migration of axon terminals or dendritic spines may be relevant during tDCS. A majority of clinical studies using tDCS employ a simplistic dose strategy where excitability is singularly increased or decreased under the anode and cathode, respectively. We discuss how this strategy, itself based on classic animal studies, cannot account for the complexity of normal and pathological brain function, and how recent studies have already indicated more sophisticated approaches are necessary. One tDCS theory regarding “functional targeting” suggests the specificity of tDCS effects are possible by modulating ongoing function (plasticity). Use of animal models of disease are summarized including pain, movement disorders, stroke, and epilepsy.
D.Q. Truong. D. Adair, M. Bikson. Computer-based models of tDCS of tACS in Transcranial Direct Current Stimulation in Neuropsychiatric Disorders: Clinical Principles ed. M.Nitsche, C. Loo and A. Brunoni 2016 10.1007/978-3-319-33967-2_5 p.47-66 . PDF
D. Ling, A. Rahman, M. Jackson M. Bikson Animal studies in the field of transcranial electric stimulation in Transcranial Direct Current Stimulation in Neuropsychiatric Disorders: Clinical Principles M.Nitsche, C. Loo and A. Brunoni 2016 10.1007/978-3-319-33967-2_5 p.67-83 PDF
Bikson M,Paneri B, Giordano J. The off-label use, utility and potential value of tDCS in the clinical care of particular neuropsychiatric conditions. Journal of Law and the Biosciences, 1–5 doi:10.1093/jlb/lsw044
Olympic Athletes Are Electrifying Their Brains, and You Can Too
If a brain-stimulation gadget catches on, expect controversy over “brain doping”
IEEE Spectrum, August 21, 2916 Link
Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016
Marom Bikson, Pnina Grossman, Chris Thomas, Adantchede Louis Zannou, Jimmy Jiang, Tatheer Adnan, Antonios P. Mourdoukoutas, Greg Kronberg, Dennis Truong, Paulo Boggio, André R. Brunoni, Leigh Charvet, Felipe Fregni, Brita Fritsch, Bernadette Gillick, Roy H. Hamilton, Benjamin M. Hampstead, Ryan Jankord, Adam Kirton, Helena Knotkova, David Liebetanz, Anli Liu, Colleen Loo, Michael A. Nitsche, Janine Reis, Jessica D. Richardson, Alexander Rotenberg, Peter E. Turkeltaub, Adam J. Woods
Brain Stimulation 2016, Vol. 9, Issue 5
Actually, just a fun image as we pilot the new headgear.
Since our lab is multidisciplinary, we have members from other fields than engineering. Selin Unal, is a medical student from Turkey that joined our lab for the summer and she is going to continue her research from Turkey remotely! See you soon Selin!
The “Non-invasive neuromodulation technology and regulation meeting” is a national meeting covering topics on the commercialization and regulation of non-invasive neuromodulation technology intended for medical and wellness use. This intensive one-day event is in direct response to the proliferation of clinical trials, popular press coverage, and now consumer-directed devices. The meeting is focused on transcranial Direct Current Stimulation (tDCS) but spans any investigational techniques or marketed technologies that apply electrical energy to the head. Ample time will be allowed for discussion with speakers.
Date: August 28, 2016
Location Center for Discovery and Innovation (CDI) Room Number – 4352
For more information visit the links below:
About this Meeting
Location
Speakers
Registration and Tickets
Program
Neural Engineering Lab members can ask for free registraton code from Dr. Marom Bikson or Bhaskar Paneri
Center of Pressure Speed Changes with tDCS Versus GVS in Patients with Lateropulsion after Stroke
Brain Stimul. 2016 Jun 21. pii: S1935-861X(16)30190-5. doi: 10.1016/j.brs.2016.06.053.
Marom Bikson speak “Brain Stimulation” at Mount Sinai for the Brain Imaging Center symposium on October 19th
Details and Registration here
