Paper published in Journal of Neuroinflammation
Voltammetry in the spleen assesses real-time immunomodulatory norepinephrine release elicited by autonomic neurostimulation
Ibrahim Mughrabi and Michael Gerber used an electrochemical method called cyclic voltammetry to measure the release of norepinephrine (NE) in the spleen in real time, in response to splenic, splanchnic and vagus nerve stimulation. Using that method, they discovered that smaller voltammetry signals, and therefore smaller amounts of NE, are associated with a stronger suppression of inflammation in an LPS challenge.
Paper published in Trends in Cardiovascular Medicine
Vagus nerve stimulation for cardiovascular diseases: Is there light at the end of the tunnel?
Stefanos Zafeiropoulos provides an overview of the rationale behind using VNS to treat cardiovascular diseases, a critical appraisal of preclinical and clinical evidence of efficacy, and a discussion of strategies to overcome challenges for clinical implementation.
Editorial commentary (by Richard Verrier)
TNP lab work on vagus nerve discussed in New Scientist article
Unravelling the secrets of the vagus nerve will revolutionize medicine
Grace Wade, after having visited the TNP lab and spent time with lab members in person, provides an insightful article on the methods we use to map the vagus nerve in humans, and the implications of this work for future therapeutics.
Paper published in Neuromodulation
Trans-spinal focused ultrasound suppresses spinal reflexes in healthy rats
Weiguo Song used focused ultrasound neuromodulation to target the spinal cord of healthy rats and found that it robustly and reversibly suppresses several spinal reflexes, including the H-reflex, windup activity of C-afferents and the withdrawal reflex. These results suggest that trans-spinal FUS may be useful in diseases of the spinal cord associated with hyper-reflexia, like spinal cord injury and painful syndromes.
Paper published in Brain Stimulation
Focused ultrasound neuromodulation of the spleen activates an anti-inflammatory response in humans
In a randomized, controlled study, Stavros Zanos and colleagues delivered a few minutes of focused ultrasound neuromodulation to the spleen of healthy humans and found that it suppresses production of TNF, a pro-inlfammatory cytokine, by 4-5 times, compared to sham stimulation.
Paper published in Brain Stimulation
Organ- and function-specific anatomical organization of vagal fibers supports fascicular vagus nerve stimulation
Co-first authors Naveen Jayaprakash, Weiguo Song and Viktor Toth (from Theo Zanos's lab) used advanced quatitative anatomy methods to describe how different types of fibers are organized inside the vagus nerve before they project to the larynx, lungs and heart; then, they used that information to deliver fascicular vagus nerve stimulation to engage different organs and functions from a single electrode device implanted in the neck.
Newly awarded $6.7M NIH-SPARC program
Reconstructing Vagal Anatomy
Stavros Zanos and the TNP lab, together with Theo Zanos and the Neural & Data Science Lab, and collaborators from Northwell Health, Zucker School of Medicine and Temple University, will lead a large-scale, quantitative anatomy program that will attempt to reconstruct at a single fiber resolution the connectivity between the vagus nerve and peripheral organs. The program is part of the NIH SPARC Phase 2.
TNP Lab in one of eigth winning teams in NIH Neuromod Prize Phase 1
Focused Ultrasound in Diabetes Mellitus Type 2 and Obesity
The winning team is led by GE Research and also includes investigators from Yale University. The project will develop a single, image-guided ultrasound treatment induces a response in the gut-brain sensory pathway to provide sustained remission in Type 2 diabetes and obesity.
Paper published in Brain Stimulation
kHz-frequency electrical stimulation selectively activates small, unmyelinated vagus afferents
Yao-Chuan Chang, post-doc at the TNP lab (and currently senior neural engineer at Medtronic) delivered kHz-frequency electrical stimulation to the vagus nerve of rats and mice, and found that it activates small unmyelinated C-type afferent fibers. C-afferents of the vagus nerve are involved in many autonomic reflexes and their selective bioelectronic modulation could create opportunities for new therapies targeting the autonomic nervous system.
TNP lab at the 5th Bioelectronic Medicine Summit
Bioelectronic Medicine: Today's Tools, Tomorrow's Therapies
The TNP lab's presence at the Summit included:
Poster: "Fascicular vagus nerve stimulation", by Weiguo Song et al.
Poster: "Chronic VNS alters T- and B-cell function in a stimulation schedule-dependent manner", by Ibrahim Mughrabi, Izumi Kato et al.
Poster: "Focused ultrasound stimulation of the spleen does not produce acute hemodynamic effects and does not elicit antidromic action potentials on the splenic nerve", by Stefanos Zafeiropoulos et al.
Session: "Neurotechnologies in the treatment of brain diseases", hosted by Stavros Zanos
Session: "Bioelectronic approaches to treating peripheral organ disorders", hosted by Stavros Zanos
Paper published in Frontiers in Immunology
Ultrasound neuromodulation of the spleen has time-dependent anti-inflammatory effect in a pneumonia model
Umair Ahmed and colleagues demonstrate that activation of the cholinergic anti-inflammatory pathway with spleen focused ultrasound (FUS) has time-dependent effect on serum cytokines in a model of pneumonia: cytokine suppression is absent at intermediate times post-infection (16 hours following inoculation), but present during the early (4 hours) and later phases (48 hours), as well as in healthy animals. The time-dependent effect could be used as a diagnostic test, even in the absence of clinical manifestations of pneumonia.
Review paper published in Bioelectronic Medicine
Strategies for precision vagus neuromodulation
Umair Ahmed, Yao-Chuan Chang and colleagues provide a detailed overview of strategies for precision neuromodulation of the vagus, including its anatomical basis, relevant technologies and translational applications in neurologic, cardiovascular and gastrointestinal diseases.
Talks at MN Neuromodulation Symposium & DMD Conference
Stavros Zanos is giving 2 talks related to vagus nerve stimulation:
Paper published in Nature Biomedical Engineering
Stimulation of the hepatoportal nerve plexus with focused ultrasound restores glucose homoeostasis in diabetic mice, rats and swine
Several members of the TNP lab, including Weiguo Song, Khaled Qanud, Jackie Tomaio and Stavros Zanos, were part of a team of investigators led by Chris Puleo (General Electric Research) that showed that noninvasive ultrasound neuromodulation of the sensory innervation of the liver results in improvement of the glycemic control in animal models of diabetes.
Paper published in Journal of the American College of Cardiology
Autonomic Neuromodulation for Atrial Fibrillation Following Cardiac Surgery
Stefanos Zafeiropoulos, graduate student at the lab, provides a summary and critical appraisal of the clinical evidence behind the use of autonomic neuromodulation for preventing post-operative atrial fibrillation, a common arrhythmia after cardiac surgery.
Lab presentations at Neural Interfaces 2021 NANS-NIC Joint Meeting
Members of the TNP lab present 3 posters and moderate 1 concurrent session:
Yao-Chuan Chang et al: KHz-frequency stimuli for selective activation of vagal C-fibers in rats and mice
Ibrahim Mughrabi et al: Real-time voltammetric detection of VNS-elicited norepinephrine release in the mouse spleen
Bioelectronic medicine: New frontiers in vagus nerve stimulation and ultrasound therapy; concurrent session moderated by Chris Puleo & Stavros Zanos, with presentations by Cristin Welle, Nikki Pelot, Sangeeta Chavan, Hubert Lim
Paper published in Cerebral Cortex
Cortical Responses to Vagus Nerve Stimulation Are Modulated by Brain State in Nonhuman Primates
Irene Rembado, post-doc at University of Washington (currently scientist at the Allen Brain Institute), and Weiguo Song, senior scientist at the TNP lab, documented how the state of the brain during different wakefulness and sleep stages shapes the cortical responses to vagus nerve stimulation in nonhuman primates.
Paper published in Journal of Neural Engineering
Implant- and anesthesia-related factors affecting cardiopulmonary threshold intensities for vagus nerve stimulation
Umair Ahmed, post-doc at the TNP lab, examined how implant age and wakefulness/anesthesia affect neurological and cardiopulmonary threshold intensities of vagus nerve stimulation in a rodent model.
Lab poster at American College of Cardiology Scientific Sessions
Umair Ahmed, post-doc at the TNP lab, discusses how focused ultrasound (FUS) neuromodulation of the inflammatory reflex at the spleen reduces the severity of pulmonary arterial hypertension in the Sugen-hypoxia rat model.
Lab presentations at IEEE EMBC Neural Engineering Conference
The TNP lab presents 1 full paper and 1 plenary talk at IEEE-EMBC NER 2021.
Laryngeal Electromyography to Estimate A-Fiber Engagement by Vagal Stimuli in Mice
Full paper, part of "Bioelectronic Medicine" session
Ibrahim Mughrabi and Adam Abbas present a method for recording laryngeal EMG in mice and its use in estimating A-fiber engagement by VNS.
Targeting of fiber subpopulations in cervical #VNS based therapies
Plenary talk, part of "Microelectodes for Small Nerves and Plexi" minisymposium
Yao-Chuan Chang and Stavros Zanos discuss ways to target selectively subpopulations of vagal fibers in the context of cervical VNS.
Paper published in eLife
Development and characterization of a chronic implant mouse model for vagus nerve stimulation
Ibrahim Mughrabi, post-doc at the TNP lab, and Jordan Hickman, research associate at Cristin Welle's lab at the University of Colorado, co-authored a paper in which they describe the surgical method for and the physiological, functional and histological characterization of a chronic mouse implant for stimulating the vagus nerve.
Paper published in Brain Stimulation
Quantitative estimation of nerve fiber engagement by vagus nerve stimulation using physiological markers
Yao-Chuan Chang, post-doc at the TNP lab, and Marina Cracchiolo, student at Silvestro Micera's lab in Scuola Superiore Sant'Anna and rotation student with Theo Zanos, co-authored a paper in which they estimated vagal fiber engagement by vagus nerve stimulation trains by looking at acute physiological responses that can be registered noninvasively.
Lab presentations at 4th Bioelectronic Medicine Summit
The TNP lab presents 3 posters and 1 plenary talk at the BEM Summit.
Factors affecting stimulation threshold in cervical VNS in rodents
Umair Ahmed et al. explain how several implant- and physiology-related factors affect the thresholds for VNS eliciting compound action potentials and physiological responses in rats.
Real-time detection of VNS-elicited NE release in the mouse spleen
Naveen Jayaprakash, Ibrahim Mughrabi et al. describe a method for detecting release of norepinephrine in the mouse spleen elicited by VNS. NE release in the spleen is a critical step in the anti-inflammatory actions of VNS.
Ultrasound neuromodulation of the porta hepatis affects insulin sensitivity in swine
Khaled Qanud et al. discuss how targeted U/S neuromodulation of the porta hepatis of the liver affects insulin sensitivity in swine, with implications in the noninvasive bioelectronic treatment of metabolic disorders such as diabetes.
Targeting populations of fibers in clinically-relevant VNS
Talk, September 23, Session 2 "Bioelectronic devices in preclinical research", 10:40-12:15
Stavros Zanos discusses clinical reasons for targeted vagal neuromodulation, methods to quantify it, and strategies for accomplishing it.
Talk at Neuroprosthetics Summer School 2020
Methods and translational applications of selective vagus nerve stimulation
Stavros Zanos discusses methods and applications of stimulating the vagus nerve to engage specific functions (afferent vs. efferent), fiber types (A, B or C), fascicles and physiological states (closed-loop stimulation).
Paper published in Scientific Reports
Anodal block permits directional vagus nerve stimulation
Umair Ahmed and Yao-Chuan Chang, post-docs at the TNP lab, co-authored a paper in which, using afferent and efferent physiological effects of VNS and stimulus-evoked compound action potentials, they demonstrated that the mechanism of anodal block permits directional VNS using rectangular waveforms.
Oral presentation at NANS 23rd Annual Meeting (Las Vegas, NV)
An implant for chronic cervical VNS in mice
Ibrahim Mughrabi, post-doc at the TNP lab, discusses the surgical technique for a novel chronic vagus nerve implant in mice, and the methodology for and results of its longitudinal in vivo physiological testing, up to 90 days post-implant.
Review paper published in Bioelectronic Medicine
Pulmonary arterial hypertension: the case for a bioelectronic treatment
Despoina Ntiloudi discusses how bioelectronic medicine, and VNS in particular, can find an application in the treatment of pulmonary arterial hypertension, a lethal disease of the pulmonary vessels and the right ventricle.
Lab posters at Society for Neuroscience 2019 Annual Meeting (Chicago, IL)
The TNP lab is represented by 3 posters at this year's Neuroscience conference.:
1. Directional biasing of vagal fiber activation using anodal block waveforms
Umair Ahmed et al. study how anodal block can be used as a method to bias afferent or efferent fiber activation in VNS
770.05/R13 (Cardiovascular regulation II)
Wed Oct 23, 1-5pm (1-2pm)
2. Vagus nerve stimulation and induced cortical plasticity in non-human primates
Irene Rembado et al. report on the effects of closed-loop VNS on brain stimulation-induced cortical plasticity in monkeys.
285.19/C10 (Spike timing-dependent plasticity)
Mon Oct 21, 8AM-12PM (10-11am)
3. In-vitro mechanical and electrical validation of a flexible microelectrode
314.22/P1 (Motor cortex and motor learning)
Mond Oct 21, 8AM-12PM (9-10AM)
Invited talk at Neuromodulation: The Science (Napa, CA)
Physiologic closed-loop control using neurostimulation
On October 5, at 9 AM (local time), Stavros Zanos will speak on using closed-loop neurostimulation to modulate dynamic physiological processes in a responsive and adaptive manner. Two applications will be discussed in more detail: induction of neuroplasticity in the central nervous system using cortical stimulation, and control of cardiac function within a desired range of parameters using vagus nerve stimulation.
More info: NTS 2019 Agenda
Invited talk at Data, Learning, Inference (DALI) 2019 (Donostia-San Sebastian, Spain)
Real-time bidirectional interfacing with the nervous system: lessons from biology and engineering
On September 5, at 6 pm(local time), Stavros Zanos will speak on the biology and engineering challenges, and ways to address them, that arise from 2 of the main requirements for a real-time bidirectional interface with the central and peripheral nervous system: the semi-real-time operation of a closed-loop system that records, analyzes and stimulates, and the maintenance of a reliable chronic interface with the nervous tissue.
More info: DALI: Brain-Machine Interfaces
Oral presentation at the 2019 IEEE Engineering in Medicine and Biology Conference (Berlin, Germany)
Extraction of evoked compound nerve action potentials from vagus nerve recordings
On July 27, at 11AM (local time), Yao-Chuan Chang, post-doc at the TNP lab, will speak on a methodology to stimulate and record evoked potentials from the vagus nerve in rats, and to suppress non-neural components of these recordings (ECG, muscle activity, stimulus artifacts). Such evoked potentials can quantify the recruitment of different types of nerve fibers by VNS and therefore used to optimize VNS therapies.
Invited Lecture at Endocrinology/ Cardiology Grand Rounds at Lenox Hill Hospital
Fiber-specific Vagus Nerve Stimulation in the Bioelectronic Treatment of Cardiovascular Disease
On Tuesday, May 7, Stavros Zanos will discuss the principles of and new techniques for fiber-specific VNS and its application in the treatment of cardiovascular diseases.
Joint GE-Feinstein paper published in Nature Communications
Noninvasive sub-organ ultrasound stimulation for targeted neuromodulation
Cotero V, Fan Y, Tsaava T, Kressel AM, Hancu I, Fitzgerald P, Wallace K, Kaanumalle S, Graf J, Rigby W, Kao T-Z, Roberts J, Bhushan C, Joel S, Coleman TR, Zanos S, Tracey KJ, Ashe J, Chavan SS, Puleo C
Posters at DARPA ElectRx/TNT PI Meeting (Boulder, CO)
Vagal-evoked cortical potentials in monkeys are modulated by brain state
Rembado I, Su D, Levari A, Shupe L, Fetz EE, Zanos S
Using implantable electronics in freely behaving monkeys, we are showing that cervical VNS elicits vagally-evoked cortical potentials that are modulated by the behavioral/brain state during which they are delivered.
Auricular vagus nerve stimulation for cortical plasticity and behavioral augmentation in monkeys
Rembado I, Su D, Boyd H, Amoeni B, Kemp I, Morse A, Birch C, Shupe L, Perlmutter S, Fetz EE, Zanos S
A closed-loop cortical stimulation (CS) paradigm that induces cortical plasticity is tested in conjunction with auricular branch VNS. We find that when VNS is delivered concurrently with CS, plasticity is reduced; when VNS is delivered at least 500 ms before CS, the plasticity effect is enhanced.
Review paper published in Cold Spring Harbor Perspectives in Medicine
Closed-loop neuromodulation in physiological and translational research
In this review, the reasons and the conditions for using closed-loop neuromodulation (CLN) are discussed, the basic components of a CLN system are described, and examples of CLN systems used in physiological and translational research are presented.
Invited presentation at Neuromodulation: The Science 2018 (Cleveland, OH)
Afferent and efferent effects of vagus nerve stimulation in different animal models
On Sunday, November 4, Stavros Zanos will discuss some of the afferent and efferent neural and physiological effects of VNS in rodents, swine and nonhuman primates, their dependence on stimulation parameters, and ways to optimize them in the context of therapeutic bioelectronic medicine applications.
Poster presentation at Society for Neuroscience 2018 Annual Meeting (San Diego, CA)
Vagal-evoked cortical potentials in monkeys follow a circadian pattern
Irene Rembado discusses the use of autonomous, portable electronics to measure and quantify monkey cortical responses to cervical VNS, as a function of cortical area, VN stimulation parameters and, more importantly, time of day; it is found that vagal-evoked potentials follow a circadian pattern.
Paper published in Current Biology
Phase-locked stimulation during cortical beta oscillations produces bidirectional synaptic plasticity in awake monkeys
Our paper on cortical oscillations, closed-loop brain stimulation and activity-dependent neural plasticity in monkeys was published on Current Biology. We find that when cortical stimulation coincides with cortical beta oscillations, short-term synaptic plasticity effects occur, whose direction (potentiation or depression) depends on the oscillatory phase at which stimulation was delivered: depolarizing phases produce potentiation, hyperpolarizing phases produce depression.
Sponsored research program at Feinstein
Bioelectronic therapy of pulmonary arterial hypertension
Over the next few years, the Translational Neurophysiology (TNP) lab will conduct preclinical research on a bioelectronic therapy of pulmonary arterial hypertension (PAH). PAH is characterized by increased resistance in the pulmonary vessels, which may progress to heart failure and death. We will test whether vagus nerve stimulation with the appropriate device, electrode, electrode placement and stimulation parameters can selectively produce vasodilation in the pulmonary circulation, relieve symptoms and delay the progression of the disease. Collaborators in this project include the Cardiopulmonary Resuscitation Lab (Lance Becker), the Bioelectronics Lab (Timir Datta), the Microfabrication Lab (Loren Rieth) and the Neural Decoding Lab (Theo Zanos).
This program is supported by a generous research grant from United Therapeutics.
Invited lecture at Experimental Biology 2018 (San Diego, CA)
Closed-loop neuromodulation in physiological and translational research
Stavros Zanos discusses the principles, uses and limitations of closed-loop neuromodulation systems in basic and translational research, and applications in clinical therapeutics.
Paper published in Frontiers in Behavioral Neuroscience
Cycle-triggered cortical stimulation during slow wave sleep facilitates learning a BMI task
Delta wave-triggered cortical stimulation leads to faster learning of a brain-machine interface task that depends on oscillatory activity from the stimulated cortical site.
Stavros Zanos joins Feinstein Institute for Medical Research
Stavros Zanos recently accepted the position of Assistant Professor at the Feinstein Institute for Medical Research, in Manhasset, New York. In his new position, Stavros will continue and expand his current research in neurophysiology and neuromodulation, develop new translational animal models to study bioelectronic medicine-based therapies and test these therapies in a variety of human diseases. [More...]
DARPA award to Stavros Zanos and Eb Fetz
VNS and neuroplasticity
Our UW group was awarded $1.3M to study the use of vagus nerve stimulation (VNS) to control brain plasticity. The 2.5-year award comes from DARPA's Targeted Neuroplasticity Training program (program officer: Doug Weber). Stavros Zanos and Eb Fetz, the two PIs, will join efforts with Steve Perlmutter, PhD, Irene Rembado, PhD, David Su, MD and a number of University of Washington scientists and students to elucidate the mechanisms through which VNS alters brain function and to leverage VNS to control targeted cortical plasticity and augment cognitive performace in nonhuman primates. The research will take place at the WA National Primate Center at the University of Washington. [More...]
UW group presentations at the Society for Neuroscience 2016 Annual Meeting (San Diego, CA)
Our groups will present the latest research findings on the effects of vagus nerve stimulation on brain function in monkeys, on inducing cortical plasticity using invasive neurostimation in humans and on a new wireless bidirectional BCI system. Also, Stavros Zanos will present the latest version of our closed-loop neurostimulation system (Neurochip3) at the CSNE booth.
Zanos S, Moorjani S, Sabesan S, Fetz EE: Effects of vagus nerve stimulation on cortical activity and excitability in the nonhuman primate [Abstract]
Ozturk Y, Su Y, Moon KS, Perlmutter S, Zanos S, Fetz EE: A wireless bidirectional brain machine interface [Abstract]
Caldwell DJ, Olson JD, Wander JD, Zanos S, Sarma D, Fetz EE, Rao R, Ojemann JG: Exploration of the phase and dose dependence of cortico-cortical evoked potentials during beta-oscillation triggered direct electrical stimulation in humans [Abstract]
UW group presentations at North American Neuromodulation Society / Neural Interfaces Joint Meeting (Baltimore, MD)
Our UW group will present 2 posters on recent work on cortical plasticity, in monkeys and humans.
Zanos S, Rembado I, Fetz E: Closed-loop ECoG Stimulation Induces Hebbian Plasticity in Sensorimotor Cortex of Awake Monkeys
Caldwell D, Olson J, Wander J, Zanos S, Sarma D, Su D, Cronin J, Collins J, Wu J, Johnson L, Weaver K, Fetz E, Rao R, Ojemann J: Enhancement of Cortico-Cortical Evoked Potentials by Beta-Oscillation Triggered Direct Electrical Stimulation in Humans
Presentations at CSNE site visit in Seattle
Our group at the annual NSF site visit to UW's CSNE had 2 presentations with latest work from the lab.
Moorjani S, Zanos S, Fetz E: Electrochemical neural interfaces for inducing motor plasticity
Bogaard A, Zanos S, Fetz E: Transcranial direct current stimulation for targeted cortical plasticity
UW group presentations at the Society for Neuroscience 2015 annual meeting (Chicago, IL)
Our group at the University of Washington presented two posters this year. Watch out for upcoming papers!
Rembado I, Zanos S, Fetz E: Effect of sleep-related cortical stimulation on learning a BCI task [Abstract]
Bogaard A, Zanos S, Richardson A, Robinson O, Fetz E: Electrical cortical stimulation paired with volitional movement produces subsequent intra- and inter-hemispheric effects in the nonhuman primate [Abstract]