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.

Prof. Marom Bikson features in “The Secret History of the Future” podcast by Slate and the Economist

Sept 12, 2018 – Episode 02: The Body Electric. Listen here

“Our mission is to reduce human suffering with technology. And we work work with all kinds of technology, including brain stimulation devices.”

Event Time and Location: Wednesday, September 12th @ 3PM in Steinman Hall Rm 402

Speaker: Jake Zabara (Inventor of Vagus Nerve Stimulation for Epilepsy and Depression)

Talk Title:  “From basic research to clinical therapy”

Current issue of Brain Stimulation (Volume 11, Issue 5) features our Dry tDCS modeling on the cover

Link: https://www.brainstimjrnl.com/issue/S1935-861X(18)X0005-9

PDF: Dry tDCS: Tolerability of a novel multilayer hydrogel composite non-adhesive electrode for transcranial direct current stimulation

Truong DQ, Bikson M. Physics of Transcranial Direct Current Stimulation Devices and Their History. J ECT. 2018;34(3):137-143.

Download: PDF published in The Journal of ECT – doi:10.1097/yct.0000000000000531

Abstract

Transcranial direct current stimulation (tDCS) devices apply direct current through electrodes on the scalp with the intention to modulate brain function for experimental or clinical purposes. All tDCS devices include a current controlled stimulator, electrodes that include a disposable electrolyte, and headgear to position the electrodes on the scalp. Transcranial direct current stimulation dose can be defined by the size and position of electrodes and the duration and intensity of current applied across electrodes. Electrode design and preparation are important for reproducibility and tolerability. High-definition tDCS uses smaller electrodes that can be arranged in arrays to optimize brain current flow. When intended to be used at home, tDCS devices require specific device design considerations. Computational models of current flow have been validated and support optimization and hypothesis testing. Consensus on the safety and tolerability of tDCS is protocol specific, but medical-grade tDCS devices minimize risk.

Khadka N, Borges H, Zannou AL, Jang J, Kim B, Lee K, Bikson M

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Download: PDF published in Brain Stimulation– DOI

Abstract

The adoption of transcranial Direct Current Stimulation (tDCS) is encouraged by portability and ease-of-use. However, the preparation of tDCS electrodes remains the most cumbersome and error-prone step. Here, we validate the performance of the first “dry” electrodes for tDCS. A “dry electrode” excludes 1) any saline or other electrolytes, that are prone to spread and leaving a residue; 2) any adhesive at the skin interface; or 3) any electrode preparation steps except the connection to the stimulator. The Multilayer Hydrogel Composite (MHC) dry-electrode design satisfied these criteria. Over an exposed scalp (supraorbital (SO) regions of forehead), we validated the performance of the first “dry” electrode for tDCS against the state-of-the-art conventional wet sponge-electrode to test the hypothesis that whether tDCS can be applied with a dry electrode with comparable tolerability as conventional “wet” techniques? MHC dry-electrode performance was verified using a skin-phantom, including mapping voltage at the phantom surface and mapping current inside the electrode using a novel biocompatible flexible printed circuit board current sensor matrix (fPCB-CSM). MHC dry-electrode performance was validated in a human trial including tolerability (VAS and adverse events), skin redness (erythema), and electrode current mapping with the fPCB-CSM. Experimental data from skin-phantom stimulation were compared against a finite element method (FEM) model. Under the tested conditions (1.5 mA and 2 mA tDCS for 20 min using MHC-dry and sponge-electrode), the tolerability was improved, and the erythema and adverse-events were comparable between the MHC dry-electrode and the state-of-the-art sponge electrodes. Dry (residue-free, non-spreading, non-adhesive, and no-preparation-needed) electrodes can be tolerated under the tested tDCS conditions, and possibly more broadly used in non-invasive electrical stimulation.

Transcutaneous auricular vagus nerve stimulation (taVNS) for improving oromotor function in newborns

Download: PDF published in Brain Stimulation – DOI

Bashar W. Badran, Dorothea D. Jenkins, William H. DeVries, Morgan Dancy, Philipp M. Summers, Georgia M. Mappin, Henry Bernstein, Marom Bikson, Patricia Coker-Bolt, Mark S. George

Download: PDF published in Scientific Reports – DOI

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

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

Download: PDF published in Frontiers in Behavioral Neuroscience – DOI

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

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

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

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

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

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

Download: PDF published in Neuromodulation – DOI

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

Abstract

Objectives

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

Materials and Methods

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

Results

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

Conclusions

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

Download: PDF published in Brain Stimulation – DOI

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

Abstract

Background

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

Objective

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

Methods

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

Results

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

Conclusions

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

Download: PDF published in Brain Stimulation – DOI

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

Abstract

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

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

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

Conference website

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

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

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

Watch the CUNY video here

You can support free toddler canes here at Safe Toddles

Download: PDF published in Brain Stimulation – DOI

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

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

Download: PDF published in Frontiers in Psychiatry – DOI

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

Abstract

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

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

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