New publication in Nature Scientific Reports

Acute effect of high‑definition and conventional tDCS on exercise performance and psychophysiological responses in endurance athletes: a randomized controlled trial

Daniel Gomes da Silva Machado, Marom Bikson, Abhishek Datta, Egas Caparelli‑Dáquer, Gozde Unal, Abrahão F. Baptista, Edilson Serpeloni Cyrino, Li Min Li , Edgard Morya, Alexandre Moreira & Alexandre Hideki Okano

Scientific Reports | (2021) 11:13911 | https://doi.org/10.1038/s41598-021-92670-6

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Abstract: Transcranial direct current stimulation (tDCS) has been used aiming to boost exercise performance and inconsistent findings have been reported. One possible explanation is related to the limitations of the so-called “conventional” tDCS, which uses large rectangular electrodes, resulting in a diffuse electric field. A new tDCS technique called high-definition tDCS (HD-tDCS) has been recently developed. HD-tDCS uses small ring electrodes and produces improved focality and greater magnitude of its aftereffects. This study tested whether HD-tDCS would improve exercise performance to a greater extent than conventional tDCS. Twelve endurance athletes (29.4 ± 7.3 years; 60.15 ± 5.09 ml kg−1 min−1) were enrolled in this single-center, randomized, crossover, and sham-controlled trial. To test reliability, participants performed two time to exhaustion (TTE) tests (control conditions) on a cycle simulator with 80% of peak power until volitional exhaustion. Next, they randomly received HD-tDCS (2.4 mA), conventional (2.0 mA), or active sham tDCS (2.0 mA) over the motor cortex for 20-min before performing the TTE test. TTE, heart rate (HR), associative thoughts, peripheral (lower limbs), and whole-body ratings of perceived exertion (RPE) were recorded every minute. Outcome measures were reliable. There was no difference in TTE between HD-tDCS (853.1 ± 288.6 s), simulated conventional (827.8 ± 278.7 s), sham (794.3 ± 271.2 s), or control conditions (TTE1 = 751.1 ± 261.6 s or TTE2 = 770.8 ± 250.6 s) [F(1.95; 21.4) = 1.537; P = 0.24; η2p = 0.123]. There was no effect on peripheral or whole-body RPE and associative thoughts (P > 0.05). No serious adverse effect was reported. A single session of neither HD-tDCS nor conventional tDCS changed exercise performance and psychophysiological responses in athletes, suggesting that a ceiling effect may exist.

Below please find information in regards to Psychology (Behavioral and Cognitive Neuroscience) PhD student lvan Iotzov’s second exam (defense of research proposal), which is open to all and will take place on Tuesday, May 25th at 11:00am via Zoom (email iiotzov@gradcenter.cuny.edu for Zoom ID). Ivan's abstract is also below.

Neural Speech Tracking: Mechanisms and Practical Applications

Speech signals have a strong and consistent effect on brain activity. Many previous studies have demonstrated the ability to find correlations between the amplitude envelope of ongoing speech and evoked responses measured through EEG or MEG. This correlation appears to be modulated by attention, as well as other high-level factors. It is of particular interest because of the possible practical applications of speech tracking in the steering of hearing aid devices and other assistive hearing devices. These devices are typically difficult to tune and the ability to use an objective neural signal as the basis for their tuning would be a great advancement in comfort and efficacy for their users. In this proposal, investigate the correlation between speech intelligibility and the neural tracking of a speech segment. We show a link between the neural tracking of speech and performance on a behavioral word-recognition task. We also develop a novel behavioral paradigm for the investigation of these effects and show preliminary data demonstrating the validity of this new paradigm. Additionally, we propose further experiments to illuminate the mechanisms behind this speech tracking phenomenon using novel manipulations of speech stimuli. Together, these aims and methods provide a basis for the use of speech tracking as an objective neural measure of intelligibility of speech and look to shed light on the oscillatory mechanisms that create the speech tracking phenomenon.

New publication in Frontiers in Neuroergonomics

Transcranial Direct Current Stimulation (tDCS) Augments the Effects of Gamified, Mobile Attention Bias Modification

Sarah Myruski, Hyein Cho, Marom Bikson, & Tracy A. Dennis-Tiwary

Frontiers in Neuroergonomics | (2021) | https://doi.org/10.3389/fnrgo.2021.652162

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Abstract: Anxiety-related attention bias (AB) is the preferential processing of threat observed in clinical and sub-clinical anxiety. Attention bias modification training (ABMT) is a computerized cognitive training technique designed to systematically direct attention away from threat and ameliorate AB, but mixed and null findings have highlighted gaps in our understanding of mechanisms underlying ABMT and how to design the most effective delivery systems. One neuromodulation technique, transcranial direct current stimulation (tDCS) across the pre-frontal cortex (PFC) may augment the effects of ABMT by strengthening top-down cognitive control processes, but the evidence base is limited and has not been generalized to current approaches in digital therapeutics, such as mobile applications. The present study was a single-blind randomized sham-controlled design. We tested whether tDCS across the PFC, vs. sham stimulation, effectively augments the beneficial effects of a gamified ABMT mobile app. Thirty-eight adults (Mage = 23.92, SD = 4.75; 18 females) evidencing low-to-moderate anxiety symptoms were randomly assigned to active or sham tDCS for 30-min while receiving ABMT via a mobile app. Participants reported on potential moderators of ABMT, including life stress and trait anxiety. ECG was recorded during a subsequent stressor to generate respiratory sinus arrhythmia (RSA) suppression as a metric of stress resilience. ABMT delivered via the app combined with tDCS (compared to sham) reduced AB and boosted stress resilience measured via RSA suppression, particularly for those reporting low life stress. Our results integrating tDCS with ABMT provide insight into the mechanisms of AB modulation and support ongoing evaluations of enhanced ABMT reliability and effectiveness via tDCS.

Dr. Mahima Sharma, Postdoctoral Fellow in Professor Parra's lab in the CCNY BME Department, is the speaker of the next BME seminar on Wednesday, May 12 at 3pm

Presentation: Synaptic evidence for the cumulative effects of weak DCS in spaced learning in rat hippocampus

Electric fields generated during direct current stimulation (DCS) are known to modulate activity dependent synaptic plasticity in-vitro. This provides a mechanistic explanation for the lasting behavioral effects observed with transcranial direct current stimulation (tDCS) in human learning experiments. However, previous in-vitro synaptic plasticity experiments show relatively small effects despite using strong fields compared to what is expected with conventional tDCS in humans (20 V/m vs. 1 V/m). We propose that effects of DCS on synaptic long-term potentiation (LTP) accumulate over time in a spaced learning paradigm, thus revealing effects at more realistic field intensities. As predicted, DCS applied during repeated bouts of theta burst stimulation (TBS) resulted in an increase of LTP. This spaced learning effect saturated quickly with strong TBS protocols and stronger fields. In contrast, weaker TBS and the weakest electric fields of 2.5 V/m resulted in the strongest relative efficacies (12% boost in LTP per 1 V/m applied). These results support the notion that the effects of weak fields during DCS accumulate through an increasing synaptic strength after repeated bouts of learning and bridge the gap in terms of efficacy between in-vitro DCS and human tDCS experiments.

Gozde Unal, a PhD student in the lab of Dr. Marom Bikson will present her defense of her research proposal on Tuesday, May 11, 2021 at 9am. A copy of her abstract is below. If you would like to attend, please contact Gozde at gunal000@citymail.cuny.edu for the Zoom meeting ID.

ADAPTIVE CURRENT-FLOW MODELS OF ECT:

EXPLAINING INDIVIDUAL STATIC IMPEDANCE, DYNAMIC IMPEDANCE, AND BRAIN CURRENT DENSITY

Abstract

Improvements in electroconvulsive therapy (ECT) outcomes have followed refinement in device electrical output and electrode montage. The physical properties of the ECT stimulus, together with those of the patient’s head, determine the impedances measured by the device and govern current delivery to the brain and ECT outcomes. However, the precise relations among physical properties of the stimulus, patient head anatomy, and patient-specific impedance to the passage of current are long-standing questions in ECT research and practice.

We developed anatomical MRI-derived models of transcranial electrical stimulation (tES) that included changes in tissue conductivity due to local electrical current flow. These “adaptive” models simulate ECT both during therapeutic stimulation using high (~1 A) current and when dynamic impedance is measured, as well as prior to stimulation when low (~1 mA) current is used to measure static impedance. We modeled two scalp layers: a superficial scalp layer with adaptive conductivity that increases with electric field up to a subject specific maximum,

(σ_SS),

and a deep scalp layer with a subject-specific fixed conductivity,

(σ_DS).

We demonstrate that variation in these scalp parameters explain clinical data on subject-specific static impedance and dynamic impedance, their imperfect correlation across subjects, their relationships to seizure threshold, and the role of head anatomy. Adaptive tES models demonstrate that current flow changes local tissue conductivity which in turn shapes current delivery to the brain in a manner not accounted for in fixed tissue conductivity models.

Our predictions that variation in individual skin properties, rather than other aspects of anatomy, largely govern the relationship between static impedance, dynamic impedance, and current delivery to the brain, are themselves subject to assumptions about tissue properties. Broadly, our novel pipeline for tES models is important in ongoing efforts to optimize devices, personalize interventions, and explain clinical findings.

Maximilian Nentwich, a PhD student in the lab of Dr. Lucas Parra will present his defense of her research proposal on Monday, May 2, 2021 at 1pm. A copy of his abstract is below. If you would like to attend, please contact Maximilian at mnentwi000@citymail.cuny.edu for the Zoom meeting ID.

NEURAL RESPONSES TO NATURALISTIC STIMULI

Maximilian Nentwich

Department of Biomedical Engineering

Mentor: Lucas C. Parra

Abstract

While experiments in neuroscience traditionally focus on well-defined static stimuli, the

results of these studies often fail to explain neural processes in naturalistic settings. Naturalistic

stimuli, like movies, allow for free eye movements and contain various complex visual, semantic

and narrative features. However, defining these features requires subjective and labor-intensive

manual annotations. Alternatively, the reliability of neural signals between brain areas or

subjects can be analyzed. This has led to the identification of brain areas that are correlated

between subjects, dependent on the narrative content of movies and the subjects attention.

Similarly, patterns of correlations between brain areas, termed ‘functional connectivity’ (FC), are

reliably activated during resting state and movie tasks.

FC has been studied extensively with fMRI, is reliable across methods and laboratories

and related to various psychiatric and demographic phenotypes. However, FC has not been

studied well in EEG. Therefore, aim 1 is to compare FC between fMRI and EEG. We

hypothesize that patterns of FC measured by fMRI and EEG are similar, and that FC in

both modalities is related to phenotypic variables. To test this, we analyzed a database of

EEG and fMRI recorded from over 1600 children and adolescents during resting state and

movie tasks. We computed FC matrices in fMRI with Pearson’s correlation, and in EEG with the

imaginary part of coherence (iCOH), a measure of phase-coupling. We then compared the

spatial patterns of FC by correlating connectivity matrices of EEG and fMRI. FC matrices of both

measures were related to phenotypes by multivariate distance matrix regression (MDMR), which

determines if differences of connectivity matrices correspond to differences in phenotypic

measures. Contrary to our hypothesis, we found that the spatial patterns of FC in EEG and fMRI

are distinct. However, FC in both modalities is related to phenotypes. We conclude that EEG

and fMRI FC reflect different neural processes.

To investigate which features of movies drive neural responses most reliably we

analyzed an additional dataset of intracranial EEG using the same movies as the FC dataset.

Movies contain several visual features, particularly temporal contrast, scene cuts, and elicit

saccades. Previous studies on fMRI and EEG suggest that motion, particularly of socially

relevant stimuli, elicits the strongest neural responses in movies. In aim 2 we test whether

motion in movies leads to neural responses in iEEG. We hypothesise that motion elicits

stronger responses than other visual features. Further, we predict that motion of

semantic objects, elicits stronger responses than other motion. We analysed the data with

a linear systems identification approach to identify the neural responses to stimuli extracted

from the movies. We could not find any significant response to optical flow, a measure of

motion. However, we found strong responses after scene cuts and saccades. Additionally,

scene cuts identified as semantic lead to different responses than scene cuts without semantic

content. We conclude that opposed to visual motion, salient novelty events drive neural

responses to movies. We further propose a recognition memory task to test whether semantic

scene cuts are better encoded in memory.

5th International Network of tES-fMRI (INTF) Webinar on Individually Optimized Non-Invasive Brain Stimulation

May 27th, 2021 for a two-hour webinar on individually optimized non-invasive brain stimulation co-hosted by Marom Bikson and Hamed Ekhtiari.

Registation and full details here

(Dr. Bikson’s presentation slides on “Closed looped stimulation: Why bother?” PDF)

In this online INTF Webinar exploring the Fundamentals & Challenges of Individually Optimized Non-Invasive Brain Stimulation, we are joined by Dr Marom Bikson (City University of New York), Dr Til Ole Bergman (University of Mainz), Dr Ines Violante (University of Surrey), Dr Romy Lorenz (University of Cambridge), Dr Alik Widge (University of Minnesota), Dr Flavio Frohlich (University of North Carolina), and Dr Hamed Ekhtiari (Laureate Institute for Brain Research) for two hours of lectures, discussions, and practical challenges, including:

• Closed-loop stimulation

• Brain-state dependent brain stimulation

• A framework for optimizing tES with closed-loop real-time fMRI

• Searching through the large brain stimulation parameter space

• What NIBS can learn from closed-loop invasive brain stimulation

• Closed-loop transcranial alternating current stimulation: Towards personalized treatments

• Online closed-loop real-time tES-fMRI: Potentials and challenges

The knowledge gained in this webinar will provide all attendees with the required knowledge to design, set up, and carry out their own optimized NIBS study, and is suitable for both new users of non-invasive brain stimulation techniques, and those with an existing knowledge of how to use these techniques

Dr. Marom Bikson speaks at Advances in Transcranial Direct Current Stimulation in Psychiatric Disorders on April 17, 2021 on “Best Practices and Latest Developments in tDCS”

Slides PDF

Zeinab Esmaeilpour, a PhD student in the lab of Dr. Marom Bikson will present her defense of her research proposal on Friday, April 2, 2021 at 3pm. A copy of her abstract is below. If you would like to attend, please contact Zeinab at zesmaei000@citymail.cuny.edu for the Zoom meeting ID.

Abstract

Understanding the cellular mechanism of direct current (DC) and kilohertz (kHz) electrical stimulation is of broad interest in neuromodulation in both invasive and noninvasive methods. More specifically there is large mismatch between enthusiasm to for clinical applications of the methods and understanding of DC and kHz mechanism of action. In the case of kilohertz stimulation, there is a well-established and validated low pass filtering characteristics of neuronal membrane. This feature attenuates sensitivity of nervous system to any waveforms with high frequency components. On the contrary, kilohertz stimulation has revolutionized spinal cord stimulation and even generated promising results in transcranial stimulation.

Effects DC stimulation have been studied in neuronal depolarization/hyperpolarization, synaptic plasticity and neuronal network modulation. Recent evidence suggests that DC stimulation can induce polarity dependent water exchange across blood brain barrier (BBB) in cell culture experiments through a mechanism called electroosmosis. Modulating water exchange rate across BBB is of broad interest in neurological disease such as dementia, Alzheimer’s, and stroke where brain clearance system is disrupted. Investigating effect of electrical stimulation on water exchange across BBB can potentially lead to therapeutic pathways.

This dissertation provides the first direct in vitro evidence on acute effects kilohertz electrical stimulation in central nervous system using both unmodulated and Amplitude-modulated waveforms. While supported by membrane characteristic of neurons, we uncovered that using low kilohertz stimulation diminishes the sensitivity of hippocampal neurons to electrical stimulation. Moreover, using Amplitude-Modulated waveform can generate a different pattern of modulation and even higher sensitivity to stimulation. However, required electric field in this case is significantly higher than low frequency stimulation methods such as tACS. We plan to study effect of direct current stimulation on water exchange rate across blood brain barrier (BBB) as new avenue of mechanism for electrical stimulation. We will investigate whether tDCS can increase water exchange rate and blood flow in healthy population using and advanced MR imaging technique.

Below please find information in regards to BME PhD student Jason Ki’s dissertation defense, which is open to all and will take place on Tuesday, March 30th at 3:00pm via Zoom. Please email Jason at jki00@citymail.cuny.edu for the Zoom link. Jason’s abstract is also below.

When the Brain Plays a Game:

Neural responses to visual dynamics during naturalistic visual tasks.

Department of Biomedical Engineering

Jason Ki

Mentor: Lucas C Parra

ABSTRACT

Many day-to-day tasks involve processing of complex visual information in a continuous stream. While much of our knowledge on visual processing has been established from reductionist approaches in lab-controlled settings, very little is known about the processing of complex dynamic stimuli experienced in everyday scenarios. Traditional investigations employ event-related paradigms that involve presentation of simple stimuli at select locations in visual space or discrete moments in time. In contrast, visual stimuli in real-life are highly dynamic, spatially-heterogeneous, and semantically rich. Moreover, traditional experiments impose unnatural task constraints (e.g. inhibited saccades), thus, it is unclear whether theories developed under the reductionist approach apply in naturalistic settings. Given these limitations, alternative experimental paradigms and analysis methods are necessary. Here, we introduce a new approach for investigating visual processing, applying the system identification (SI) framework. We investigate the modulation of stimulus-evoked responses during a naturalistic task (i.e. kart race game) using non-invasive scalp recordings.

In recent years, multivariate modeling approaches have become increasingly popular for assessing neural response to naturalistic stimulus. Encoding models use stimulus patterns to predict brain responses and decoding models use patterns of brain responses to predict stimulus that drove these responses. In this dissertation, we employ a hybrid method that “encodes” the stimulus to predict “decoded” brain responses. With this approach, we measure the stimulus-response correlation (SRC, i.e. temporal correlation of neural response and dynamic stimulus) to assess the strength of stimulus-evoked activity to uniquely experienced naturalistic stimulus. To demonstrate this, we measured the SRC during a kart race videogame. We find that SRC increased with active play of the game, suggesting that stimulus-evoked activity is modulated by the visual task demands. Furthermore, we analyzed the selectivity of neural response across the visual space. While it is well-established that neural response is spatially selective to discrete stimulus, it is unclear whether this is true during naturalistic stimulus presentation. To assess this, we measured the correlation of neural response with optical flow magnitude at individual locations on the screen during the videogame. We find that the SRC is greater for locations in space that are task-relevant, enhancing during active play. Moreover, the spatial selectivity differs across scalp locations, which suggest that individual brain regions are spatially selective to different visual dynamics.

Overall, we leveraged the SI framework to investigate visual processing during a naturalistic stimulus presentation, extending visual research to ecologically valid paradigms. Our findings shed new insights about the stimulus-evoked neural response to visual dynamics during a uniquely experienced naturalistic visual task. We show that selectivity of neural response can be spatially-resolved at pixel-level from a low-SNR EEG. In the future, by further probing other spatial and temporal dimensions of the stimuli (beyond optical flow), we may gain new insights into how neural signals convey visual processing during dynamic natural visual experiences.

New publication in frontiers in Human Neuroscience

International Consensus Based Review and Recommendations for Minimum Reporting Standards in Research on Transcutaneous Vagus Nerve Stimulation (Version 2020)

Adam D. Farmer, Adam Strzelczyk, Alessandra Finisguerra, Alexander V. Gourine, Alireza Gharabaghi, Alkomiet Hasan, Andreas M. Burger, Andrés M. Jaramillo, Ann Mertens, Arshad Majid, Bart Verkuil, Bashar W. Badran, Carlos Ventura-Bort, Charly Gaul, Christian Beste, Christopher M. Warren, Daniel S. Quintana, Dorothea Hämmerer, Elena Freri, Eleni Frangos, Eleonora Tobaldini, Eugenijus Kaniusas, Felix Rosenow, Fioravante Capone, Fivos Panetsos, Gareth L. Ackland, Gaurav Kaithwas, Georgia H. O'Leary, Hannah Genheimer, Heidi I. L. Jacobs, Ilse Van Diest, Jean Schoenen, Jessica Redgrave, Jiliang Fang, Jim Deuchars, Jozsef C. Széles, Julian F. Thayer, Kaushik More, Kristl Vonck, Laura Steenbergen, Lauro C. Vianna, Lisa M. McTeague, Mareike Ludwig, Maria G. Veldhuizen, Marijke De Couck, Marina Casazza, Marius Keute, Marom Bikson, Marta Andreatta, Martina D'Agostini, Mathias Weymar, Matthew Betts, Matthias Prigge, Michael Kaess, Michael Roden, Michelle Thai, Nathaniel M. Schuster, Nicola Montano, Niels Hansen, Nils B. Kroemer, Peijing Rong, Rico Fischer, Robert H. Howland, Roberta Sclocco, Roberta Sellaro, Ronald G. Garcia, Sebastian Bauer, Sofiya Gancheva, Stavros Stavrakis, Stefan Kampusch, Susan A. Deuchars, Sven Wehner, Sylvain Laborde, Taras Usichenko, Thomas Polak, Tino Zaehle, Uirassu Borges, Vanessa Teckentrup, Vera K. Jandackova, Vitaly Napadow, & Julian Koenig

Frontiers in Human Neuroscience | (2021) 14:568051 | https://doi.org10.3389/fnhum.2020.568051

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Abstract: Given its non-invasive nature, there is increasing interest in the use of transcutaneous vagus nerve stimulation (tVNS) across basic, translational and clinical research. Contemporaneously, tVNS can be achieved by stimulating either the auricular branch or the cervical bundle of the vagus nerve, referred to as transcutaneous auricular vagus nerve stimulation(VNS) and transcutaneous cervical VNS, respectively. In order to advance the field in a systematic manner, studies using these technologies need to adequately report sufficient methodological detail to enable comparison of results between studies, replication of studies, as well as enhancing study participant safety. We systematically reviewed the existing tVNS literature to evaluate current reporting practices. Based on this review, and consensus among participating authors, we propose a set of minimal reporting items to guide future tVNS studies. The suggested items address specific technical aspects of the device and stimulation parameters. We also cover general recommendations including inclusion and exclusion criteria for participants, outcome parameters and the detailed reporting of side effects. Furthermore, we review strategies used to identify the optimal stimulation parameters for a given research setting and summarize ongoing developments in animal research with potential implications for the application of tVNS in humans. Finally, we discuss the potential of tVNS in future research as well as the associated challenges across several disciplines in research and clinical practice.

A subject in Marom Bikson’s research group using the taVNS device with telemedicine support.

While COVID’s often deadly outcome has resulted in the worst pandemic in a century, studies are unveiling a post-COVID phase for survivors during which neuropsychiatric symptoms, such as fatigue, anxiety and depression, can occur. How to treat this debilitating phase, called NeuroCOVID, is the challenge City College of New York biomedical engineer Marom Bikson and his team are tackling.

The first stage of COVID is characterized by fever, heart or lung problems. NeuroCOVID is second stage, characterized by one or a combination of symptoms like vertigo, loss of smell, headaches, fatigue and irritability, as well as anxiety and depression, said Bikson, professor in the Grove School of Engineering. These second stage symptoms can persist, leaving patients with ongoing mental health complications. 

Bikson is leading a multi-center trial utilizing a revolutionary noninvasive technology developed in his neural engineering lab. It involves stimulating the vagus nerve in an attempt to both directly activate brain healing mechanisms and also reduce inflammation in participants with reported neuroCOVID symptoms. Using this two-prong approach, which aims to reverse neuropathic changes in brain function while also reducing inflammation (which is known to cause a host of problems in the body) it is hoped that some or all of the patients’ neuroCOVID symptoms will subside.

In addition to state-of-the-art technology to activate the nervous system, the clinical trial incorporates advanced home-based real-time monitoring of patient vitals, and a clinician-patient portal for real-time assessment of progress and remote-control of the technology. “This is truly personalized medicine, with the ability for physicians to adjust therapy in real-time and monitor patient progress at-home with rigor usually reserved for advanced medical centers. The trial is one example of hundreds of medical treatments developed at CCNY being tested or in use,” said Bikson.

The device used in the trial includes a small clip placed on the ear. A hand-held stimulator provides barely perceptible electrical stimulation to the ear to stimulate the auricula branch of the vagus nerve. The technique is generally called transcutaneous Auricular Nerve Stimulation or tAVNS. The Bikson group worked with clinicians at the Medical University of South Carolina (MUSC) to optimize tAVNS so it can be used reliably and easily in patients’ homes. The partners also designed a trial allowing entirely home-based treatment for NeuroCOVID.

Bikson directs one of the most productive medical device design labs in the country with support from the National Institutes of Health and numerous corporate partners. It develops medical devices to treat neurological and psychiatric disorders, including devices that apply minute levels of energy to activate the brain and nervous system. 

The devices for the NeuroCOVID trial are built by Soterix Medical, a medical device company co-founded by Bikson as a spin-off from CCNY research.  

About the City College of New York
Since 1847, The City College of New York has provided a high-quality and affordable education to generations of New Yorkers in a wide variety of disciplines. CCNY embraces its position at the forefront of social change. It is ranked #1 by the Harvard-based Opportunity Insights out of 369 selective public colleges in the United States on the overall mobility index. This measure reflects both access and outcomes, representing the likelihood that a student at CCNY can move up two or more income quintiles. In addition, the Center for World University Rankings places CCNY in the top 1.8% of universities worldwide in terms of academic excellence. Labor analytics firm Emsi puts at $1.9 billion CCNY’s annual economic impact on the regional economy (5 boroughs and 5 adjacent counties) and quantifies the “for dollar” return on investment to students, taxpayers and society. At City College, more than 16,000 students pursue undergraduate and graduate degrees in eight schools and divisions, driven by significant funded research, creativity and scholarship. CCNY is as diverse, dynamic and visionary as New York City itself. View CCNY Media Kit.

New publication in Brain Stimulation

Alternate sessions of transcranial direct current stimulation (tDCS) reduce chronic pain in women affected by chikungunya. A randomized clinical trial

Clécio Gabriel de Souza, Rodrigo Pegado, Jardson Fausto da Costa, Edgard Morya, Abrahão Baptista, Gozde Unal, Marom Bikson, & Alexandre Hideki Okano

Brain Stimulation | (2021) | https://doi.org/10.1016/j.brs.2021.02.015

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Abstract:

Context

Thousands of people worldwide have been infected by the chikungunya virus (CHIKV), and the persistence of joint pain symptoms has been considered the main problem. The mechanisms of neuropathic pain include cortical areas. Neuromodulation techniques such as transcranial direct current stimulation (tDCS) act on brain areas involved in the processing of chronic pain. It was previously demonstrated that tDCS for five consecutive days significantly reduced pain in the chronic phase of chikungunya (CHIK).

Objective

To analyze the effect of alternate tDCS sessions on pain and functional capacity in individuals affected by CHIK.

Methods

In a randomized clinical trial, 58 women in the chronic phase of CHIK were divided into two groups: active tDCS (M1-S0, 2mA, 20 minutes) and sham. The Visual Analogue Scale (VAS) and Brief Pain Inventory (BPI) were used to assess pain, while the Health Assessment Questionnaire (HAQ) assessed functional capacity. These scales were used before and after six sessions of tDCS in nonconsecutive days on the primary motor cortex, and at follow-up consultation 7 and 15 days after the last session. A repeated measures mixed-model ANOVA was used for comparison between groups (significant p-values < 0.05).

Results

A significant pain reduction (Z[3, 171] = 14.303; p < 0.0001) was observed in the tDCS group compared to the sham group; no significant difference in functional capacity was observed (Z[1.57] = 2.797; p = 0.1).

Conclusion

Our results suggest that six nonconsecutive sessions of active tDCS on M1 reduce pain in chronic CHIKV arthralgia.

Forouzan V. Farahani, a PhD student in the lab of Dr. Lucas Parra will present her defense of her research proposal on Tuesday, March 9, 2021 at 9:30am. A copy of her abstract is below. If you would like to attend, please contact Forouzan at fvasheg000@citymail.cuny.edu for the Zoom meeting ID.

Abstract

Transcranial direct current stimulation (tDCS) involves low-intensity electrical current applied to the brain via electrodes placed over the scalp. This technique has gained attention due to putative improvements in brain function and the potential to treat brain-related disorders. Various aspects of tDCS, including safety, simplicity, and affordability, have drawn interest as an alternative treatment. Nonetheless, the efficacy of this technique is open to discussion. An important question about the effectiveness of tDCS is whether its effects can last after the period of stimulation. The lasting effects of this technique are thought to be mediated by synaptic plasticity. Several studies have found DCS-induced effects on synaptic plasticity in animal models. Yet, there is no direct evidence associating neuronal excitability to synaptic plasticity.

One promising application of tDCS is the modulation of motor excitability and motor learning. Functional and structural changes in the primary motor cortex (M1) have been associated with motor skill learning. Therefore, human and animal tDCS studies have targeted this region to modulate motor learning. However, there are ongoing debates about the efficacy of low-intensity tDCS, the underlying mechanism explaining the results, and the importance of online versus offline tDCS with learning. This dissertation provides the first direct in vitro evidence linking the effects of DCS on neuronal membrane potential and excitability to Hebbian synaptic plasticity. While this mechanism now has some support, we also uncovered that it could not fully account for the effects of DCS on plasticity. We propose that DCS also affects plasticity via the propagation of its effects over recurrent excitatory connections combined with a homeostatic plasticity mechanism. We plan to study the effect of anodal tDCS on enhancing motor skill learning in rats in vivo. We will investigate whether the effects are due to sensation or stress. Moreover,

Neuromodulation techniques for Alzheimer’s disease and age-related cognitive decline.

By Marom Bikson (City College of New York)

Even as the societal burden of Alzheimer’s disease and related dementias increases, pharmaceutical trials targeting the associated toxic protein aggregates have disappointed. Neuromodulation devices apply energy (eg, electrical or ultrasound) to the brain to promote the recovery of function. As an alternative to pharmacologic interventions (drug therapies), neuromodulation therapies are non-systemic and can directly target brain regions with stimulation waveforms designed to boost specific brain processes.

Neuromodulation devices can be surgically implanted or used non-invasively (on the scalp). Noninvasive neuromodulation treatments can involve repeated visits to a clinic, whereas some devices can be used at home. Neuromodulation therapies are established for indications such as depression, pain, epilepsy, and Parkinson’s disease, and include patients who were not responsive to drug therapies. Neuromodulation trials show promise in maintaining, and even reversing, cognitive decline in Alzheimer’s and related neurodegenerative disorders.

A neuromodulation technique using “shockwave” ultrasound received regulatory medical CE approval for use in Alzheimer’s disease and mild-to-moderate dementia. Patients who received this noninvasive, painless treatment at outpatient clinics over the course of six visits within 2 weeks showed neuropsychological improvements lasting at least 3 months. (1) Not to be confused with transcranial focused ultrasound stimulation, “shockwave” ultrasound applies isolated acoustic pulses that in turn enhance neurovascular function. (2)

A wearable neuromodulation technique called transcranial direct current stimulation (tDCS) is also actively trialed for Alzheimer’s and age-related cognitive decline. tDCS is suitable even for at-home use (it could be made available over the counter) and may provide unique therapeutic potency by “cleansing the brain.”

More plaques versus less clearance in Alzheimer’s disease: chicken and egg

A key question in Alzheimer’s disease research is: how much of the accumulation of toxic protein aggregates reflect abnormal production versus disrupted clearance  mechanisms? (3) Therapeutically, this is a moot point unless we have treatments that can boost brain clearance.

Accumulation of toxic protein aggregates-amyloid-β (Aβ) plaques and hyperphosphorylated tau tangles is the pathologic hallmark of Alzheimer’s disease; however, drug trials targeting these proteins have been unsuccessful.

Because they remove cellular waste products and deliver nutrients to the interstitial space (the space around neurons), the clearance systems of the brain are critical for normal brain function. Brain interstitial fluid clearance systems become disrupted with Alzheimer’s disease progression.(4)

Interstitial fluid clearance mechanisms may also be generally compromised with age, which may further be linked to the role of clearance during sleep.(5,6)

How transcranial direct current stimulation works

Go with the (blood) flow

Transcranial direct current stimulation (tDCS) applies a low fixed-intensity (direct current) electrical current to the brain through electrodes placed on the scalp. Powered by a 9-volt battery, tDCS is painless, safe, and can be administered at home. (7,8)

Like most other treatments of brain disease, neurons are the de facto target of tDCS.

Adverse effects of tDCS are very mild, including tingling or itching sensations that resolve as stimulation ends, and skin reddening (erythema) that can persist a while longer. Given this sign of profound change in blood flow at the scalp by tDCS, one may ask: could changes in neurovascular function also be occurring?

In fact, there is extensive brain imaging data of the brain vascular response to tDCS. However, as is typically the case with brain imaging techniques that rely on hemodynamic response (eg, blood-oxygen-level-dependent imaging functional MRI), this vascular response is considered an epiphenomenon, which means the detection of vascular action is presumed to be secondary to neuronal stimulation.

This makes sense based on the underlying principle of neurovascular coupling: cerebral blood supply is increased in response to neuronal metabolic activity, as well as to remove toxic byproducts from the interstitial space. But could tDCS swap the regular order of neurovascular coupling: activating blood flow first, which then leads to secondary neuronal modulation? These questions are hard to answer, precisely because neuronal activity and brain vasculature are intimately linked. To convincingly show a primary vascular response, one would require a “brain” consisting of vasculature but no neurons.

Blood vessel walls, including those making up neuronal vasculature, are formed by endothelial cells, which are the barrier between the brain’s interstitial space and circulating blood. This blood–brain-barrier (BBB) is an exceptionally regulated barrier as a result of tight bonds between endothelial cells, known as tight junctions. Cultured endothelial cells on a filter form a BBB model, which can be absent of other cells types. Using such a model, we showed that direct current stimulation directly activates endothelial cells, thereby providing direct evidence of how brain vasculature could respond to  tDCS. (9)

We showed that the neurovascular endothelial cells that make up the BBB are a direct cellular target of tDCS, which supports ongoing trials where activating brain blood flow can support recovery of function (eg, in acute  stroke). (10)

Further analyses of the mechanism’s underlying BBB stimulation led us to a novel therapeutic pathway for Alzheimer’s disease: boosting brain clearance.

Flush and rinse

Direct current stimulation drove water transport across the BBB model through the mechanism of electro-osmosis, which occurs when electrical current flowing through a network of cells produces an associated drag on water. The smaller the gap between cells, the more electro-osmosis, and the BBB is exceptionally tight. Moreover, when the current flow is in a sustained direction, as is the case for tDCS, so is the water flow.

Along with water flow, we showed boosting of specific molecule transport and endothelial-cell gene activation. We reproduced our finding that tDCS boosts transport across the BBB in an intact animal model.(11)

We made a further striking discovery: in addition to enhancing transport across the BBB, tDCS also increased diffusivity within the brain interstitial space.(12)

Taken together, this indicates that tDCS, a noninvasive neuromodulation technique with minimal side effects, could boost brain clearance by both driving water across the BBB and enhancing transport around neurons.

Ongoing and future clinical trials: treating Alzheimer’s disease with tDCS

In patients with Alzheimer’s disease or age-related atypical cognitive impairment, clinical trials with tDCS treatment have been completed, and expanded trials are ongoing. The National Institutes of Health (NIH)-funded study Augmenting Cognitive Training in Older Adults (ACT) is a Phase 3, definitive, multi-site, randomized clinical trial of 360 older adults to establish the benefit of delivering tDCS to remediate age-related cognitive decline. (13)

The randomized controlled Prevention of Alzheimer’s dementia with Cognitive remediation plus tDCS in Mild cognitive impairment and Depression (PACt-MD) study includes 375 older participants with either atypical cognitive impairment and/or major depression.(14)

While most trials evaluate in-clinical treatment, an NIH-funded, randomized, double-blind trial study at Albert Einstein College of Medicine, Bronx, NY, will evaluate the effects of 6 months of at-home tDCS in 100 patients with mild-to-moderate Alzheimer's disease.(15)

The Veterans Administration and NIH are supporting two double-blind, randomized, controlled trials in patients with mild cognitive impairment (146 patients) or Alzheimer’s disease (100 patients) using High-Definition tDCS, a form of tDCS that can focally target brain regions.(16,17)

These studies will further use imaging to evaluate changes in both cerebral blood and amyloid and tau plaque severity.

Clinical trials of tDCS around the world are recruiting hundreds more older adults with mild cognitive impairment, Alzheimer’s disease, and related dementia. These trials were founded on the established actions of tDCS on neurons, including promoting synaptic plasticity. But tDCS may also be boosting brain vascular function and driving brain clearance mechanisms. Even as definitive clinical data on the treatment of age-related cognitive decline continue to emerge, further work characterizing these special mechanisms of tDCS can be used to optimize therapies.

Key points

• Neuromodulation devices are non-drug therapies designed to boost specific therapeutic mechanisms.

• Transcranial direct current stimulation (tDCS) is a wearable device that is actively trialed for the treatment of Alzheimer’s disease and mild cognitive impairment.

• In addition to stimulating neurons, tDCS enhances brain blood flow and clearance mechanisms.

• The boosting of brain clearance mechanism by tDCS is a powerful mechanism to reverse the build-up of toxic proteins associated with Alzheimer’s disease.

References

1. Beisteiner R, Matt E, Fan C, et al. Transcranial pulse stimulation with ultrasound in Alzheimer's disease–a new navigated focal brain therapy. Adv Sci (Weinh). 2019;7:1902583.

2. Hatanaka K, Ito K, Shindo T, et al. Molecular mechanisms of the angiogenic effects of low-energy shock wave therapy: roles of mechanotransduction. Am J Physiol Cell Physiol. 2016;311:C378-385.

3. Tarasoff-Conway JM, Carare RO, Osorio L, et al. Clearance systems in the brain–implications for Alzheimer disease. Nat Rev Neurol. 2015;11:457-470.

4. Peng W, Achariyar TM, Li B, et al. Suppression of glymphatic fluid transport in a mouse model of Alzheimer's disease. Neurobiol Dis. 2016;93:215-225.

5. Kress BT, Iliff JJ, Xia M, Wang M, et al. Impairment of paravascular clearance pathways in the aging brain. Ann Neurol. 2014;76:845-861.

6. Xie L, Kang H, Xu Q, et al. Sleep drives metabolite clearance from the adult brain. Science. 2013;342:373-377.

7. Bikson M, Grossman P, Thomas C, et al. Safety of transcranial direct current stimulation: evidence based update 2016. Brain Stimul. 2016;9:641-661. PDF

8. Charvet LE, Kasschau M, Datta A, et al. Remotely-supervised transcranial direct current stimulation (tDCS) for clinical trials: guidelines for technology and protocols. Front Syst Neurosci. 2015;9:26.

9. Cancel LM, Arias K, Bikson M, Tarbell JM. Direct current stimulation of endothelial monolayers induces a transient and reversible increase in transport due to the electroosmotic effect. Sci Rep. 2018;8:9265. PDF

10. NCT03574038. Transcranial direct current stimulation as a neuroprotection in acute stroke (TESSERACT).https://clinicaltrials.gov/ct2/show/NCT03574038.Accessed November 28, 2020.

11. Shin DW, Fan J, Luu E, et al. In vivo modulation of the blood-brain barrier permeability by transcranial direct current stimulation (tDCS). Ann Biomed Eng. 2020;48:1256-1270.

12. Xia Y, Khalid W, Yin Z, Huang G, Bikson M, Fu BM. Modulation of solute diffusivity in brain tissue as a novel mechanism of transcranial direct current stimulation (tDCS). Sci Rep. 2020;10:18488.

13. NCT02851511. Augmenting cognitive training in older adults (ACT).https://clinicaltrials.gov/ct2/show/NCT02851511. Accessed November 28, 2020.

14. NCT02386670. Prevention of Alzheimer's disease with CR plus tDCS in mild cognitive impairment and depression (PACt-MD) (PACt-MD).https://www.clinicaltrials.gov/ct2/show/NCT02386670. Accessed November 28, 2020.

15. NCT04404153. NeurostImulation for cognitive enhancement in Alzheimer's disease (NICE-AD).https://clinicaltrials.gov/ct2/show/NCT04404153. Accessed November 28, 2020.

16. NCT02155946. Promoting adaptive neuroplasticity in mild cognitive impairment.https://clinicaltrials.gov/ct2/show/NCT02155946. Accessed November 28, 2020.

17. NCT03875326. Stimulation to improve memory (STIM).https://clinicaltrials.gov/ct2/show/NCT03875326. Accessed November 28, 2020.

New publication in Physiology & Behavior

Effect of tDCS on well-being and autonomic function in professional male players after official soccer matches

Alexandre Moreira, Daniel Gomes da Silva Machado, Luciane Moscaleski, Marom Bikson, Gozde Unal, Paul S Bradley, Abrahão F Baptista, Edgard Morya, Thais Cevada, Lucas Marques, Vinicius Zanetti, & Alexandre Hideki Okano

Physiology & Behavior | (2021) | https://doi.org/10.1016/j.physbeh.2021.113351

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Abstract: This study aimed to examine the effect of transcranial direct current stimulation (tDCS) used as a recovery strategy, on heart rate (HR) measures and perceived well-being in 12 male professional soccer players. tDCS was applied in the days after official matches targeting the left dorsolateral prefrontal cortex (DLPFC) with 2 mA for 20 min (F3-F4 montage). Participants were randomly assigned to anodal tDCS (a-tDCS) or sham tDCS sessions. Players completed the Well-Being Questionnaire (WBQ) and performed the Submaximal Running Test (SRT) before and after tDCS. HR during exercise (HRex) was determined during the last 30 s of SRT. HR recovery (HRR) was recorded at 60 s after SRT. The HRR index was calculated from the absolute difference between HRex and HRR. A significant increase was observed for WBQ (effect of time; p<0.001; ηp2=0.417) with no effect for condition or interaction. A decrease in HRR (p=0.014; ηp2=0.241), and an increase in HRR index were observed (p=0.045; ηp2=0.168), with no effect for condition or interaction. No change for HRex was evident (p>0.05). These results suggest that a-tDCS over the DLPFC may have a positive effect on enhancing well-being and parasympathetic autonomic markers, which opens up a possibility for testing tDCS as a promising recovery-enhancing strategy targeting the brain in soccer players. The findings suggest that brain areas related to emotional and autonomic control might be involved in these changes with a possible interaction effect of tDCS by placebo-related effects, but more research is needed to verify this effect.

Dr. Marom Bikson speaks on Jan 15th 2020 at the North American Neuromodulation Society (NANS) anual meeting (online).

“Spinal Cord Stimulation (SCS): Subthreshold Actions” Slides PDF

Dr. Bikson also serves on the Scientific Program Committee for NANS 2020 and organizes / chairs several sessions around engineering and basic science topics.

Dr. Marom Bikson writes an Expert Point of View for Neurodiem on “Wearable neuromodulation devices that flush the brain: a promising tool against Alzheimer’s disease”

Read the paper here (free sign up may be required)

Key points in article

• Neuromodulation devices are nondrug therapies designed to boost specific therapeutic mechanisms.

• Transcranial direct current stimulation (tDCS) is a wearable device that is actively trialed for the treatment of Alzheimer’s disease and mild cognitive impairment.

• In addition to stimulating neurons, tDCS enhances brain blood flow and clearance mechanisms.

• The boosting of brain clearance mechanism by tDCS is a powerful mechanism to reverse the build-up of toxic proteins associated with Alzheimer’s disease.

Engineering principles of SCS and DBS: Foundations, industry updates, and emerging concepts

on: Thursday January 14, 2021 10am – 6:30pm ET

As free conference/ Information and registation here

The conference is co-chaired by Marom Bikson and Scott Lempka.

Dr. Bikson will also lecture on “Neurostimulation fundamentals: Dose, current flow, and neural activation” Download slides.

New publication in Neuromodulation: Technology at the Neural Interface

Neurocapillary‐Modulation

Niranjan Khadka and Marom Bikson.

Neuromodulation: Technology at the Neural Interface 2020. DOI: https://doi.org/10.1111/ner.13338

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Abstract

Objectives

We consider two consequences of brain capillary ultrastructure in neuromodulation. First, blood‐brain barrier (BBB) polarization as a consequence of current crossing between interstitial space and the blood. Second, interstitial current flow distortion around capillaries impacting neuronal stimulation.

Materials and Methods

We developed computational models of BBB ultrastructure morphologies to first assess electric field amplification at the BBB (principle 1) and neuron polarization amplification by the presence of capillaries (principle 2). We adapt neuron cable theory to develop an analytical solution for maximum BBB polarization sensitivity.

Results

Electrical current crosses between the brain parenchyma (interstitial space) and capillaries, producing BBB electric fields (EBBB) that are >400x of the average parenchyma electric field (ĒBRAIN), which in turn modulates transport across the BBB. Specifically, for a BBB space constant (λBBB) and wall thickness (dth‐BBB), the analytical solution for maximal BBB electric field (EABBB) is given as: (ĒBRAIN × λBBB)/dth‐BBB. Electrical current in the brain parenchyma is distorted around brain capillaries, amplifying neuronal polarization. Specifically, capillary ultrastructure produces ~50% modulation of the ĒBRAIN over the ~40 μm inter‐capillary distance. The divergence of EBRAIN (Activating function) is thus ~100 kV/m2 per unit ĒBRAIN.

Conclusions

BBB stimulation by principle 1 suggests novel therapeutic strategies such as boosting metabolic capacity or interstitial fluid clearance. Whereas the spatial profile of EBRAIN is traditionally assumed to depend only on macroscopic anatomy, principle 2 suggest a central role for local capillary ultrastructure—which impact forms of neuromodulation including deep brain stimulation (DBS), spinal cord stimulation (SCS), transcranial magnetic stimulation (TMS), electroconvulsive therapy (ECT), and transcranial electrical stimulation (tES)/transcranial direct current stimulation (tDCS).

. Application of neurocapillary-modulation in neuromodulation simulations of tES, DBS, and SCS.