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.

Hadar R, Winter R, Callesen HE, Wieske F, Habelt B, Khadka N, Felgel-Farnholz V, Barroeta-Hlusicka E, Reis J, Tatarau CA, Funke K, Fritsch B, Bernhardt N, Bikson M, Nitsche MA, Winter C. 2018. Prevention of schizophrenia deficits via non-invasive adolescent frontal cortex stimulation in rats. Nature Molecular Psychiatry. 2019. https://doi.org/10.1038/s41380-019-0356-x. PDF

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Download: PDF published in Nature Molecular Psychiatry – DOI

Abstract

Schizophrenia is a severe neurodevelopmental psychiatric affliction manifested behaviorally at late adolescence/early adulthood. Current treatments comprise antipsychotics which act solely symptomatic, are limited in their effectiveness and often associated with side-effects. We here report that application of non-invasive transcranial direct current stimulation (tDCS) during adolescence, prior to schizophrenia-relevant behavioral manifestation, prevents the development of positive symptoms and related neurobiological alterations in the maternal immune stimulation (MIS) model of schizophrenia.

Title: Neurocognitive mechanisms of DLPFC tDCS in major depressive disorder

Speaker: Dr. Maria Ironside, Post Doctoral Research Fellow, Center for Depression, Anxiety and Stress Research, McLean Hospital – Harvard Medical School

When: Friday Feb. 1 2019 at 1 pm

Where: CCNY Center for Discovery and Innovation, 4th floor seminar room (CDI 4.352)

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

Abstract:

The difficulty in treating mood and anxiety disorders has sparked clinical interest in novel treatments, such as transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC). However, underlying mechanisms of action are unclear. It is established that people with mood and anxiety disorders have negative cognitive biases, such as increased vigilance to threat. Psychiatric treatments have acute effects on these cognitive biases which predict later therapeutic action. Such effects are proposed as cognitive biomarkers of response.

A healthy volunteer investigation revealed an anxiolytic like effect (reduced threat vigilance) of a single session of tDCS on a behavioural test of proven clinical relevance (Ironside et al., 2016, Biological Psychiatry). Complementing these data, we used functional imaging to reveal that, in a sample of trait anxious females, tDCS of the DLPFC increased activation in an attentional control network and reduced amygdala response to fearful face distractors (Ironside et al., 2018, JAMA Psychiatry). This provides causal evidence that modulating activity in the DLPFC inhibits amygdala response to threat, providing a potential neural mechanism for the previous reduction in vigilance to threat. Collectively, these results propose an emerging neurocognitive model for the mechanisms of action of tDCS. We also examined pairing tDCS with attentional bias modification training and found no effect of stimulation.

Together, findings point to an anxiolytic-like effect of DLPFC tDCS on cognitive and neural biomarkers relevant to mood and anxiety disorders, indicating potential cognitive and underlying neural mechanisms that may mediate the reported clinical efficacy of DLPFC tDCS. This has implications as the identification of treatment response markers could aid patient selection for future trials and ultimately treatment selection for patients.

Adair, Devin, Dennis Q. Truong, Libby Ho, Bashar W. Badran, Helen Borges, and Marom Bikson. 2019. Abstract #124: How to modulate cognition with cranial nerve stimulation? Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e42-3, https://doi.org/10.1016/j.brs.2018.12.131.

Bikson, M. 2019. Downloading personalized brain stimulation. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): 424, https://doi.org/10.1016/j.brs.2018.12.375.

Chhatbar, Pratik Y., Steven A. Kautz, Istvan Takacs, Nathan C. Rowland, Gonzalo J. Revuelta, Mark S. George, Marom Bikson, and Wuwei Feng. 2019. Abstract #22: First report of recording transcranial direct current stimulation-generated electric fields in subthalamic nuclei using directional leads. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e8, https://doi.org/10.1016/j.brs.2018.12.029.

DaFonseca, Estevão, Alexandre F. DaSilva, Marom Bikson, Dennis Troung, and Marcos F. DosSantos. 2019. Proceedings #21: Specific patterns of current flow generated by different tDCS montages in the midbrain and in the trigeminal brainstem sensory nuclear complex. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e84-6, https://doi.org/10.1016/j.brs.2018.12.190.

Datta, Abhishek, Yu Huang, Chris Thomas, Marom Bikson, and Ahmed Duke Shereen. 2019. Proceedings #12: Influence of incorporating electrode information from MR images: Towards building more realistic forward models. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e72-4, https://doi.org/10.1016/j.brs.2018.12.181.

Esmaeilpour, Z., M. Jackson, G. Kronberg, T. Zhang, R. Esteller, B. Hershey, and M. Bikson. 2019. Effect of kHz electrical stimulation on hippocampal brain slice excitability and network dynamics. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): 586, https://doi.org/10.1016/j.brs.2018.12.948.

Esmaeilpour, Zeinab, Ahmed Duke Shereen, Marom Bikson, and Hamed Ekhtiari. 2019. Abstract #147: MRI neuroimaging methods for tDCS: A methodological note on study design and parameter space. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e50, https://doi.org/10.1016/j.brs.2018.12.154.

Fallahrad, Mohamad, Louis Zannou, Niranjan Khadka, Steven A. Prescott, Stéphanie Ratté, Tianhe Zhang, Rosana Esteller, Brad Hershey, and Marom Bikson. 2019. Abstract #159: Hardware suitable for electrophysiology and stimulation in kHz range. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e54, https://doi.org/10.1016/j.brs.2018.12.166.

Favoretto, Diandra B., Eduardo Bergonzoni, Diego Nascimento, Brunna Rimoli, Tenysson Will-Lemos, Dennis Q. Truong, Renato Moraes, et al. 2019. Abstract #119: Polarity-dependent effects on postural control after high-definition transcranial direct current stimulation over the temporo-parietal junction. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e41, https://doi.org/10.1016/j.brs.2018.12.126.

Fonteneau, Clara, Marine Mondino, Martijn Arns, Chris Baeken, Marom Bikson, Andre R. Brunoni, Matthew J. Burke, et al. Sham tDCS: A hidden source of variability? reflections for further blinded, controlled trials. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation (2019/01), https://doi.org/10.1016/j.brs.2018.12.977.

Gebodh, Nigel, Zeinab Esmaeilpour, Devin Adair, Kenneth Chelette, Jacek Dmochowski, Lucas Parra, Adam J. Woods, Emily S. Kappenman, and Marom Bikson. 2019. Abstract #125: Failure of conventional signal processing techniques to remove “Physiological” artifacts from EEG during tDCS. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e43, https://doi.org/10.1016/j.brs.2018.12.132.

Gebodh, Nigel, Laura Vacchi, Devin Adair, Gozde Unal, Alexander Poltorak, Valeria Poltorak, and Marom Bikson. 2019. Proceedings #11: Replay of endogenous sleep rhythms to produce sleepiness. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e71-2, https://doi.org/10.1016/j.brs.2018.12.180.

Huang, Y., A. Datta, M. Bikson, and L. Parra. 2019. ROAST: A fully-automated, open-source, realistic vOlumetric-approach-based simulator for TES. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): 391, https://doi.org/10.1016/j.brs.2018.12.253.

Huang, Y., and L. Parra. 2019. Deep brain areas can be reached by transcranial electric stimulation with multiple electrodes. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): 390-1, https://doi.org/10.1016/j.brs.2018.12.252.

Huang, Yu, Chris Thomas, Abhishek Datta, and Lucas C. Parra. 2019. Proceedings #23: Inaccurate segmentation of lesioned brains can significantly affect targeted transcranial electrical stimulation on stroke patients. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e87-9, https://doi.org/10.1016/j.brs.2018.12.192.

Jiang, Jimmy, Dennis Q. Truong, and Marom Bikson. 2019. Abstract #115: What is theoretically more focal: HD-tDCS or TMS? Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e39-40, https://doi.org/10.1016/j.brs.2018.12.122.

Jiang, Jimmy, Dennis Q. Truong, Yu Huang, Lucas Parra, and Marom Bikson. 2019. Abstract #118: Transcranial electrical stimulation models using an emulated-CSF value approximate the meninges more accurately. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e40-1, https://doi.org/10.1016/j.brs.2018.12.125.

Khadka, N., A. Zannou, D. Truong, T. Zhang, R. Esteller, B. Hersey, and M. Bikson. 2019. Generation 2 kilohertz spinal cord stimulation (kHz-SCS) bioheat multi-physics model. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): 566, https://doi.org/10.1016/j.brs.2018.12.876.

Khadka, Niranjan, Helen Borges, Trynia Kauffman, Alain Pascal, Bhaskar Paneri, Electra Nassis, Yungjae Shin, et al. 2019. Abstract #109: Tolerability of an adaptive-tDCS upto 4 mA using subject assessment and machine-learning to optimize dose. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e37-8, https://doi.org/10.1016/j.brs.2018.12.116.

Khadka, Niranjan, Helen Borges, Adantchede L. Zannou, Jongmin Jang, Byungjik Kim, Kiwon Lee, and Marom Bikson. 2019. Abstract #100: Dry tDCS: Tolerability of a novel multilayer hydrogel composite non-adhesive electrode for tDCS. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e35, https://doi.org/10.1016/j.brs.2018.12.107.

Kronberg, G., A. Rahman, M. Bikson, and L. Parra. 2019. A hebbian framework for predicting modulation of synaptic plasticity with tDCS. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): 554, https://doi.org/10.1016/j.brs.2018.12.831.

Kronberg, Greg, Asif Rahman, Marom Bikson, and Lucas Parra. 2019. Abstract #122: A hebbian framework for predicting modulation of synaptic plasticity with tDCS. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e42, https://doi.org/10.1016/j.brs.2018.12.129.

Louviot, Samuel, Jacek Dmochowski, Jacques Jonas, Louis Maillard, Sophie Colnat-Coulbois, Louise Tyvaert, and Laurent Koessler. 2019. Abstract #32: Medial and lateral temporal lobe neuromodulation in epilepsy: A simultaneous tdcs-seeg investigation. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e12, https://doi.org/10.1016/j.brs.2018.12.039.

Louviot, Samuel, Jacek Dmochowski, Jacques Jonas, Louis Maillard, Sophie Colnat-Coulbois, Louise Tyvaert, and Laurent koessler. 2019. Abstract #68: A human in-vivo evaluation of roast using simultaneous intracerebral electrical stimulations and scalp eeg. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e24, https://doi.org/10.1016/j.brs.2018.12.075.

Lucas Parra, Yu Huang. 2019. Abstract #38: Transcranial electric stimulation with multiple electrodes can reach deep brain areas. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e14, https://doi.org/10.1016/j.brs.2018.12.045.

Meiron, Oded, Rena Gale, Julia Namestnic, Odeya Bennet-Back, Jonathan David, Nigel Gebodh, Devin Adair, Zeinab Esmaeilpour, and Marom Bikson. 2019. Abstract #123: Attenuation of pathological EEG features in nonatal electroclinical syndromes: HD-tDCS in catastrophic epilepsies. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e42, https://doi.org/10.1016/j.brs.2018.12.130.

Mourdoukoutas, Antonios, Gozde Unal, John Martin, Mar Cortes, Jeremy Fidock, and Marom Bikson. 2019. Proceedings #14: Neuromodulation of spinal cord with tDCS extracephalic return electrode. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e75-6, https://doi.org/10.1016/j.brs.2018.12.183.

Quinn, Davin, Joel Upston, Thomas Jones, Jessica Richardson, Lindsay Worth, Violet Fratzke, Julia Stephen, et al. 2019. Abstract #1: Individualizing HD-tDCS with fMRI and E-field modeling: Pilot data from the NAVIGATE-TBI study. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e1, https://doi.org/10.1016/j.brs.2018.12.008.

Salvi, Carola, Ryan D. Conrardy, Marom Bikson, Mark Beeman, and Jordan Grafman. 2019. Abstract #142: Effects of high definition tDCS on problem solving networks. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e49, https://doi.org/10.1016/j.brs.2018.12.149.

Shaw, M., N. Pawlak, C. Choi, N. Khan, A. Datta, and M. Bikson. 2019. Transcranial direct current stimulation (tDCS) induces acute changes in brain metabolism. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): 518, https://doi.org/10.1016/j.brs.2018.12.703.

Shereen, D., and L. Parra. 2019. Rapid measurement of electromagnetic fields induced from transcranial electric stimulation using magnetic resonance imaging. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): 584, https://doi.org/10.1016/j.brs.2018.12.938.

Shereen, Duke, and Lucas Parra. 2019. Abstract #98: Rapid field mapping using magnetic resonance imaging during transcranial direct current stimulation. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e34, https://doi.org/10.1016/j.brs.2018.12.105.

Tarbell, John, Marom Bikson, Limary M. Cancel, and Niranjan Khadka. 2019. Abstract #33: Direct current stimulation of endothelial monolayers induces an increase in transport by the electroosmotic effect. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e12, https://doi.org/10.1016/j.brs.2018.12.040.

Trapp, Nicholas T., Willa Xiong, Britt M. Gott, Gemma D. Espejo, Marom Bikson, and Charles R. Conway. 2019. Proceedings #51: 4 mA adaptive transcranial direct current stimulation for treatment-resistant depression: Early demonstration of feasibility with a 20-session course. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e124-5, https://doi.org/10.1016/j.brs.2018.12.220.

Truong, Dennis Q., Catherine Maglione, Yishai Valter, Louis Zannou, A. D. Shereen, Preston Williams, John H. Martin, and Marom Bikson. 2019. Abstract #29: Scaling spinal cord injury models for non-invasive stimulation. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e10-1, https://doi.org/10.1016/j.brs.2018.12.036.

Unal, Gozde, Bronte N. Ficek, Kimberly T. Webster, Syed Shahabuddin, Dennis Q. Truong, Marom Bikson, and Kyrana Tsapkini. 2019. Abstract #113: Individualized modeling for subjects with primary progressive aphasia. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e39, https://doi.org/10.1016/j.brs.2018.12.120.

Valero-Cabre, Antoni, Clara Sanches, Dennis Q. Truong, Marom Bikson, and Marc Teichmann. 2019. Abstract #2: Improvement of language function following prefrontal transcranial direct current brain stimulation in progressive supranuclear palsy. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e1-2, https://doi.org/10.1016/j.brs.2018.12.009.

Williams, Preston, John Brandenburg, Dennis Q. Truong, Alan C. Seifert, Adrish Sarkar, Junqian Xu, Marom Bikson, and John Martin. 2019. Abstract #136: Translational neuromodulation of motor-output using trans-spinal direct current stimulation (tsDCS) in a large animal model. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e46-7, https://doi.org/10.1016/j.brs.2018.12.143.

Zannou, Adantchede L., Niranjan Khadka, Mohamad FallahRad, Dennis Truong, and Marom Bikson. 2019. Abstract #30: Tissue temperature increases by HF10 senza spinal cord stimulation system: Phantom and bioheat model. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation 12 (2) (03/01; 2019/01): e11, https://doi.org/10.1016/j.brs.2018.12.037.

Fonteneau C, Mondino M, Arns M, Baeken C, Bikson M, Brunoni AR, Burke MJ, Neuvonen T, Padberg F, Pascual-Leone A, Poulet E, Ruffini G, Santarnecchi E, Sauvaget A, Schellhorn K, Suaud-Chagny M-F, Palm U, Brunelin J. Sham tDCS: a hidden source of variability? Reflections for further blinded, controlled trials. Brain Stimulation. https://doi.org/10.1016/j.brs.2018.12.977 (In Press). 2019

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Download: PDF published in Brain Stimulation – DOI

Abstract
Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique increasingly used to modulate neural activity in the living brain. In order to establish the neurophysiological, cognitive or clinical effects of tDCS, most studies compare the effects of active tDCS to those observed with a sham tDCS intervention. In most cases, sham tDCS consists in delivering an active stimulation for a few seconds to mimic the sensations observed with active tDCS and keep participants blind to the intervention. However, to date, sham-controlled tDCS studies yield inconsistent results, which might arise in part from sham inconsistencies. Indeed, a multiplicity of sham stimulation protocols is being used in the tDCS research field and might have different biological effects beyond the intended transient sensations. Here, we seek to enlighten the scientific community to this possible confounding factor in order to increase reproducibility of neurophysiological, cognitive and clinical tDCS studies.

da S. Machado D. G., Unal G., Andrade S. M., Moreira A., Altimari L. R., Brunoni A. R., Perrey S., Mauger A. R., Bikson M., Okano, A. H. (2018). Effect of transcranial direct current stimulation on exercise performance: A systematic review and meta-analysis. Brain Stimulation. 12(3), 593–605. https://doi.org/10.1016/j.brs.2018.12.227 PDF

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Abstract: Transcranial direct current stimulation (tDCS) has been used to improve exercise performance, though the protocols used, and results found are mixed. We aimed to analyze the effect of tDCS on improving exercise performance. A systematic search was performed on the following databases, until December 2017: PubMed/MEDLINE, Embase, Web of Science, SCOPUS, and SportDiscus. Full-text articles that used tDCS for exercise performance improvement in adults were included. We compared the effect of anodal (anode near nominal target) and cathodal (cathode near nominal target) tDCS to a sham/control condition on the outcome measure (performance in isometric, isokinetic or dynamic strength exercise and whole-body exercise). 22 studies (393 participants) were included in the qualitative synthesis and 11 studies (236 participants) in the meta-analysis. The primary motor cortex (M1) was the main nominal tDCS target (n = 16; 72.5%). A significant effect favoring anodal tDCS (a-tDCS) applied before exercise over M1 was found on cycling time to exhaustion (mean difference = 93.41 s; 95%CI = 27.39 s–159.43 s) but this result was strongly influenced by one study (weight = 84%), no effect was found for cathodal tDCS (c-tDCS). No significant effect was found for a-tDCS applied on M1 before or during exercise on isometric muscle strength of the upper or lower limbs. Studies regarding a-tDCS over M1 on isokinetic muscle strength presented mixed results. Individual results of studies using a-tDCS applied over the prefrontal and motor cortices either before or during dynamic muscle strength testing showed positive results, but performing meta-analysis was not possible. For the protocols tested, a-tDCS but not c-tDCS vs. sham over M1 improved exercise performance in cycling only. However, this result was driven by a single study, which when removed was no longer significant. Further well-controlled studies with larger sample sizes and broader exploration of the tDCS montages and doses are warranted.

Dobbs B., Pawlak N., Biagioni M., Agarwal S., Shaw M., Pilloni G., Bikson M., Datta A., Charvet L. (2018). Generalizing remotely supervised transcranial direct current stimulation (tDCS): feasibility and benefit in Parkinson’s disease. Journal of NeuroEngineering and Rehabilitation, 15(1). https://doi.org/10.1186/s12984-018-0457-9

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Download: PDF published in Journal of NeuroEngineering and Rehabilitation – DOI

Abstract: Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that has been shown to improve common symptoms of neurological disorders like depressed mood, fatigue, motor deficits and cognitive dysfunction. tDCS requires daily treatment sessions in order to be effective. We developed a remotely supervised tDCS (RS-tDCS) protocol for participants with multiple sclerosis (MS) to increase accessibility of tDCS, reducing clinician, patient, and caregiver burden. The goal of this protocol is to facilitate home use for larger trials with extended treatment periods. In this study we determine the generalizability of RS-tDCS paired with cognitive training (CT) by testing its feasibility in participants with Parkinson’s disease (PD). Following the methods in our MS protocol development, we enrolled sixteen participants (n = 12 male, n = 4 female; mean age 66 years) with PD to complete ten open-label sessions of RS-tDCS paired with CT (2.0 mA × 20 min) at home under the remote supervision of a trained study technician. Tolerability data were collected before, during, and after each individual session. Baseline and follow-up measures included symptom inventories (fatigue and sleep) and cognitive assessments. RS-tDCS was feasible and tolerable for patients with PD, with at-home access leading to high protocol compliance. Side effects were mostly limited to mild sensations of transient itching and burning under the electrode sites. Similar to prior finding sin MS, we found preliminary efficacy for improvement of fatigue and cognitive processing speed in PD. RS-tDCS paired with CT is feasible for participants with PD to receive at home treatment. Signals of benefit for reduced fatigue and improved cognitive processing speed are consistent across the PD and MS samples. RS-tDCS can be generalized to provide tDCS to a range of patients with neurologic disorders for at-home rehabilitation.

Marom Bikson featured in Daily Beast article on brain stimulation “Flow Neuroscience Advertises Pumping Electricity Into Your Own Brain at Home. Should You Do It?”  Dec 2, 2018

Article is here

Lee S. H., Im J. J., Oh J. K., Choi E. K., Yoon S., Bikson M., Song I.-U., Jeong H., Chung Y-A. (2018). Transcranial direct current stimulation for online gamers: A prospective single-arm feasibility study. Journal of Behavioral Addictions, 1–5. Akademiai Kiado Zrt. Retrieved from http://dx.doi.org/10.1556/2006.7.2018.107

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Download: PDF published in Journal of Behavioral Addictions – DOI

Abstract: Excessive use of online games can have negative influences on mental health and daily functioning. Although the effects of transcranial direct current stimulation (tDCS) have been investigated for the treatment of addiction, it has not been evaluated for excessive online game use. This study aimed to investigate the feasibility and tolerability of tDCS over the dorsolateral prefrontal cortex (DLPFC) in online gamers. A total of 15 online gamers received 12 active tDCS sessions over the DLPFC (anodal left/cathodal right, 2 mA for 30 min, 3 times per week for 4 weeks). Before and after tDCS sessions, all participants underwent 18F-fluoro-2-deoxyglucose positron emission tomography scans and completed the Internet Addiction Test (IAT), Brief Self Control Scale (BSCS), and Beck Depression Inventory-II (BDI-II). After tDCS sessions, weekly hours spent on games (p = .02) and scores of IAT (p < .001) and BDI-II (p = .01) were decreased, whereas BSCS score was increased (p = .01). Increases in self-control were associated with decreases in both addiction severity (p = .002) and time spent on games (p = .02). Moreover, abnormal right-greater-than-left asymmetry of regional cerebral glucose metabolism in the DLPFC was partially alleviated (p = .04). Our preliminary results suggest that tDCS may be useful for reducing online game use by improving interhemispheric balance of glucose metabolism in the DLPFC and enhancing self-control. Larger sham-controlled studies with longer follow-up period are warranted to validate the efficacy of tDCS in gamers.

Gebodh, N., Esmaeilpour, Z., Adair, D., Chelette, K., Dmochowski, J., Woods, A. J., Kappenman, E. S., Parra L. C., Bikson M. (2019). Inherent physiological artifacts in EEG during tDCS. NeuroImage, 185, 408–424. Elsevier BV.

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Download: PDF published in NeuroImage – DOI

Abstract

Online imaging and neuromodulation is invalid if stimulation distorts measurements beyond the point of accurate measurement. In theory, combining transcranial Direct Current Stimulation (tDCS) with electroencephalography (EEG) is compelling, as both use non-invasive electrodes and image-guided dose can be informed by the reciprocity principle. To distinguish real changes in EEG from stimulation artifacts, prior studies applied conventional signal processing techniques (e.g. high-pass filtering, ICA). Here, we address the assumptions underlying the suitability of these approaches. We distinguish physiological artifacts – defined as artifacts resulting from interactions between the stimulation induced voltage and the body and so inherent regardless of tDCS or EEG hardware performance – from methodology-related artifacts – arising from non-ideal experimental conditions or non-ideal stimulation and recording equipment performance. Critically, we identify inherent physiological artifacts which are present in all online EEG-tDCS: 1) cardiac distortion and 2) ocular motor distortion. In conjunction, non-inherent physiological artifacts which can be minimized in most experimental conditions include: 1) motion and 2) myogenic distortion. Artifact dynamics were analyzed for varying stimulation parameters (montage, polarity, current) and stimulation hardware. Together with concurrent physiological monitoring (ECG, respiration, ocular, EMG, head motion), and current flow modeling, each physiological artifact was explained by biological source-specific body impedance changes, leading to incremental changes in scalp DC voltage that are significantly larger than real neural signals. Because these artifacts modulate the DC voltage and scale with applied current, they are dose specific such that their contamination cannot be accounted for by conventional experimental controls (e.g. differing stimulation montage or current as a control). Moreover, because the EEG artifacts introduced by physiologic processes during tDCS are high dimensional (as indicated by Generalized Singular Value Decomposition- GSVD), non-stationary, and overlap highly with neurogenic frequencies, these artifacts cannot be easily removed with conventional signal processing techniques. Spatial filtering techniques (GSVD) suggest that the removal of physiological artifacts would significantly degrade signal integrity. Physiological artifacts, as defined here, would emerge only during tDCS, thus processing techniques typically applied to EEG in the absence of tDCS would not be suitable for artifact removal during tDCS. All concurrent EEG-tDCS must account for physiological artifacts that are a) present regardless of equipment used, and b) broadband and confound a broad range of experiments (e.g. oscillatory activity and event related potentials). Removal of these artifacts requires the recognition of their non-stationary, physiology-specific dynamics, and individualized nature. We present a broad taxonomy of artifacts (non/stimulation related), and suggest possible approaches and challenges to denoising online EEG-tDCS stimulation artifacts.

Silva-Filho, E., Okano, A. H., Morya, E., Albuquerque, J., Cacho, E., Unal, G., Bikson, M., et al. (2018). Neuromodulation treats Chikungunya arthralgia: a randomized controlled trial. Scientific Reports, 8(1). Springer Nature America, Inc.

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Download: PDF published in Scientific Reports – DOI

Abstract

The Chikungunya (CHIK) virus is epidemic in Brazil, with 170,000 cases in the first half of 2016. More than 60% of patients present relapsing and remitting chronic arthralgia with debilitating pain lasting years. There are no specific therapeutic agents to treat and rehabilitee infected persons with CHIK. Persistent pain can lead to incapacitation, requiring long-term pharmacological treatment. Advances in non-pharmacological treatments are necessary to promote pain relief without side effects and to restore functionality. Clinical trials indicate transcranial direct current stimulation (tDCS) can treat a broad range of chronic pain disorders, including diffuse neuromuscular pain and arthralgia. Here, we demonstrate that the tDCS across the primary motor cortex significantly reduces pain in the chronic phase of CHIK. High-resolution computational model was created to analyze the cortical electric field generated during tDCS and a diffuse and clustered brain current flow including M1 ipsilateral and contralateral, left DLPFC, nucleus accumbens, and cingulate was found. Our findings suggest tDCS could be an effective, inexpensive and deployable therapy to areas lacking resources with a significant number of patients with chronic CHIK persistent pain.

Zannou, A. L.*, Khadka, N.*, Truong, D. Q., Zhang, T., Esteller, R., Hershey, B., & Bikson, M. 2018. Temperature increases by kilohertz frequency spinal cord stimulation.

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Download: PDF published in Brain Stimulation – DOI

Abstract

Kilohertz frequency spinal cord stimulation (kHz-SCS) deposits significantly more power in tissue compared to SCS at conventional frequencies, reflecting increased duty cycle (pulse compression). We hypothesize kHz-SCS increases local tissue temperature by joule heat, which may influence the clinical outcomes. To establish the role of tissue heating in KHZ-SCS, a decisive first step is to characterize the range of temperature changes expected during conventional and KHZ-SCS protocols. Fiber optic probes quantified temperature increases around an experimental SCS lead in a bath phantom. These data were used to verify a SCS lead heat-transfer model based on joule heat. Temperature increases were then predicted in a seven-compartment (soft tissue, vertebral bone, fat, intervertebral disc, meninges, spinal cord with nerve roots) geometric human spinal cord model under varied parameterization. The experimentally constrained bio-heat model shows SCS waveform power (waveform RMS) determines tissue heating at the spinal cord and surrounding tissues. For example, we predict temperature increased at dorsal spinal cord of 0.18e1.72 ° C during 3.5 mA peak 10 KHz stimulation with a 40-10- 40 ms biphasic pulse pattern, 0.09e0.22 ° C during 3.5 mA 1 KHz 100-100-100 ms stimulation, and less than 0.05 ° C during 3.5 mA 50 Hz 200-100-200 ms stimulation. Notably, peak heating of the spinal cord and other tissues increases superlinearly with stimulation power and so are especially sensitive to in- cremental changes in SCS pulse amplitude or frequency (with associated pulse compression). Further supporting distinct SCS intervention strategies based on heating; the spatial profile of temperature changes is more uniform compared to electric fields, which suggests less sensitivity to lead position. Tissue heating may impact short and long-term outcomes of KHZ-SCS, and even as an adjunct mechanism, suggests distinct strategies for lead position and programming optimization.

Santos, T. E. . G., Favoretto, D. B., Toostani, I. G., Nascimento, D. C., Rimoli, B. P., Bergonzoni, E., et al. (2018). Manipulation of Human Verticality Using High. Frontiers in Neurology 64(2), p. 825.

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Download: PDF published in Frontiers in Neurology – DOI

Abstract

Using conventional tDCS over the temporo-parietal junction (TPJ) we previously reported that it is possible to manipulate subjective visual vertical (SVV) and postural control. We also demonstrated that high-definition tDCS (HD-tDCS) can achieve substantially greater cortical stimulation focality than conventional tDCS. However, it is critical to establish dose-response effects using well-defined protocols with relevance to clinically meaningful applications. To conduct three pilot studies investigating polarity and intensity-dependent effects of HD-tDCS over the right TPJ on behavioral and physiological outcome measures in healthy subjects. We additionally aimed to establish the feasibility, safety, and tolerability of this stimulation protocol. We designed three separate randomized, double-blind, crossover phase I clinical trials in different cohorts of healthy adults using the same stimulation protocol. The primary outcome measure for trial 1 was SVV; trial 2, weight-bearing asymmetry (WBA); and trial 3, electroencephalography power spectral density (EEG-PSD). The HD-tDCS montage comprised a single central, and 3 surround electrodes (HD-tDCS3x1) over the right TPJ. For each study, we tested 3×2 min HD-tDCS3x1 at 1, 2 and 3 mA; with anode center, cathode center, or sham stimulation, in random order across days. We found significant SVV deviation relative to baseline, specific to the cathode center condition, with consistent direction and increasing with stimulation intensity. We further showed significant WBA with direction governed by stimulation polarity (cathode center, left asymmetry; anode center, right asymmetry). EEG-PSD in the gamma band was significantly increased at 3 mA under the cathode. The present series of studies provide converging evidence for focal neuromodulation that can modify physiology and have behavioral consequences with clinical potential.

Combined mnemonic strategy training and high-definition transcranial direct current stimulation for memory deficits in mild cognitive impairment

Download: PDF published in Alzheimer’s & Dementia: Translational Research & Clinical Interventions doi.org/10.1016/j.trci.2017.04.008

Benjamin M. Hampstead, Krishnankutty Sathian, Marom Bikson, Anthony Y. Stringer

ABSTRACT

Introduction: Memory deficits characterize Alzheimer’s dementia and the clinical precursor stage known as mild cognitive impairment. Nonpharmacologic interventions hold promise for enhancing functioning in these patients, potentially delaying functional impairment that denotes transition to dementia. Previous findings revealed that mnemonic strategy training (MST) enhances long-term retention of trained stimuli and is accompanied by increased blood oxygen level–dependent signal in the lateral frontal and parietal cortices as well as in the hippocampus. The present study was designed to enhance MST generalization, and the range of patients who benefit, via concurrent delivery of transcranial direct current stimulation (tDCS).

Methods: This protocol describes a prospective, randomized controlled, four-arm, double-blind study targeting memory deficits in those with mild cognitive impairment. Once randomized, participants complete five consecutive daily sessions in which they receive either active or sham high definition tDCS over the left lateral prefrontal cortex, a region known to be important for successful memory encoding and that has been engaged by MST. High definition tDCS (active or sham) will be combined with either MST or autobiographical memory recall (comparable to reminiscence therapy). Participants undergo memory testing using ecologically relevant measures and functional magnetic resonance imaging before and after these treatment sessions as well as at a 3-month follow-up. Primary outcome measures include face-name and object-location association tasks. Secondary outcome measures include self-report of memory abilities as well as a spatial navigation task (near transfer) and prose memory (medication instructions; far transfer). Changes in functional magnetic resonance imaging will be evaluated during both task performance and the resting-state using activation and connectivity analyses.

Discussion: The results will provide important information about the efficacy of cognitive and neuromodulatory techniques as well as the synergistic interaction between these promising approaches. Exploratory results will examine patient characteristics that affect treatment efficacy, thereby identifying those most appropriate for intervention.

Title: Safe Direct Current Neural Implant

Speaker: Gene Y. Fridman, PhD.  Associate Professor, Johns Hopkins University, Departments of Otolaryngology Head and Neck Surgery, Biomedical Engineering and Electrical Engineering

When: Friday Oct. 5 2018 at 2 pm

Where: CCNY Center for Discovery and Innovation, 4th floor seminar room ( CDI 4.352)

Details: Safe DC Neural Implant, Gene Y. Fridman

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

Abstract:

Safe Direct Current Stimulation (SDCS) technology holds the promise for the creation of a new class
of neural implants that could expand our ability to interact with the human nervous system.
Pacemakers, cochlear implants, and essentially all other chronically implanted neuroelectronic
prostheses rely on charge-balanced, biphasic pulses to excite neural or muscular activity without driving
electrochemical reactions that would otherwise liberate toxic substances at the metal electrode-saline
interface. While these devices are effective at stimulating the target neurons, inhibition of neural
activity and further expansion into alternate modes of neural control have been more challenging.
Many neurologic deficits, such as balance disorders, inability to control micturition, tinnitus, chronic
pain, psychiatric disorders, and epilepsy could benefit from a neural implant capable more extensive
control of neural activity. In contrast to the brief biphasic stimulus pulse used to evoke an action
potential in a target neuron, ionic direct current (iDC) delivered by an extracellular electrode has a
graded effect on its membrane potential. As the result, iDC is capable of increasing or decreasing the
probability of action potential generation. Excitation delivered this way results in an increase in neural
activity that maintains its natural stochastic firing properties. In addition to being able to increase,
decrease, or altogether block spiking behavior, this neuromodulation mechanism can control the speed
of action potential propagation, modulate sensitivity to synaptic input, and in principle alter synaptic
weights in a neural network by modulating spike timing dependent plasticity.
I will address our latest efforts toward developing the SDCS implant capable of delivering iDC to
neural targets and the application of this new technology for the treatment of chronic peripheral pain
and for the treatment of the vestibular balance disorders.

Bio:

Dr. Gene Fridman is a Biomedical and Electrical engineer. He is an Associate Professor in the department of Otolaryngology Head and Neck Surgery in the School of Medicine and Biomedical and Electrical Engineering departments in the Whiting School of Engineering at Johns Hopkins University.  After receiving his Master of Science in Electrical Engineering from Purdue University in 1995, he worked in the aerospace and then in the biomedical industry as a software and systems engineer before deciding to engage in an academic career. He received his Ph.D. in Biomedical Engineering specializing in neural recording and stimulation and micro-electro-mechanical systems (MEMS) from UCLA in 2006. Since 2000 he has held an on-going consulting and collaborative relationship with biomedical engineering companies in research and design of neural stimulation and recording devices. He contributed to research and development of spinal cord, retinal, cortical, cochlear, and vestibular neural implants.