News

Fall 2023

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 link

Summer 2023

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.

Paper link

Editorial commentary (by Richard Verrier)

Summer 2023

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.

Article link

Summer 2023

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 link

Spring 2023

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.

Open-access paper

Press coverage by Focused Ultrasound Foundation

Press coverage by Science News

Winter 2022-2023

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. 

Open-access paper

Press coverage by Business Wire

Fall 2022

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.

Northwell Health press release

Press coverage by Bio-IT World

NIH Common Fund Award Announcement

Fall 2022

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.

Neuromod Prize Phase 1 Winning Teams

Fall 2022

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.

Open-access paper

Fall 2022

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:

Event page

Media coverage

Summer 2022

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.

Journal link

Author copy

Spring 2022

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.

Journal link

Author copy

Spring 2022

Talks at MN Neuromodulation Symposium & DMD Conference

Vagus neuromodulation

Stavros Zanos is giving 2 talks related to vagus nerve stimulation:

Design of Medical Devices Conference 2022, April 13, 2022

Session: Neurorobotics & Neuromodulation

MN Neuromodulation Symposium 2022, Thursday April 14, 2022

Session: Closing the Loop

Spring 2022

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.

Journal link

Author copy

Winter 2021-2022

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.

Journal link

Author copy

Podcast discussion by Valentin Fuster, JACC Senior Editor

Coverage by MedScape Cardiology

Coverage by This Week in Cardiology Podcast

Coverage by BioSpace

Summer 2021

Lab presentations at Neural Interfaces 2021 NANS-NIC Joint Meeting

Members of the TNP lab present 3 posters and moderate 1 concurrent session:


Summer 2021

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. 

Open-access paper

Coverage by Psychology Today

Coverage by Genetic Engineering & Biotechnology News


Summer 2021

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. 

Open-access paper

Coverage by BusinessWire

Spring 2021

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. 

Abstract 


Spring 2021

Electricity in Physiology & Medicine 

A brief account by David M. Warmflash on how the physics of electromagnetism started merging with physiology and medicine through a scientific and philosophical rivalry b/w two Italian giants: Galvani and Volta.

Medscape article

PDF copy


Spring 2021

OpEd: On the cusp of bioelectronic medicine breakthroughs 

Stavros Zanos provides a short overview of preclinical and clinical research from the past year on the use of bioelectronic medicine to treat chronic diseases. 

HealthTechHotSpot article

PDF copy


Spring 2021

Lab presentations at IEEE EMBC Neural Engineering Conference 

The TNP lab presents 1 full paper and 1 plenary talk at IEEE-EMBC NER 2021.


Spring 2021

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. 

Open-access paper

Coverage by Technology Networks

Fall 2020

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.

Open-access paper

Coverage by Psychology Today

Fall 2020

Lab presentations at 4th Bioelectronic Medicine Summit 

The TNP lab presents 3 posters and 1 plenary talk at the BEM Summit.

Poster abstracts from Bioelectronic Medicine journal


Summer 2020

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).

Schedule

Spring 2020

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.

Open-access paper

Discussion of the paper from Ruairi Mackenzie

Coverage by Business Wire

Winter 2019-20

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. 

Abstract

Coverage by Innovate LI portal

Winter 2019-20

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.

Open access paper

Coverage by Pulmonary Hypertension News

Fall 2019

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

2. Vagus nerve stimulation and induced cortical plasticity in non-human primates

3. In-vitro mechanical and electrical validation of a flexible microelectrode

Fall 2019

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

Fall 2019

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

Summer 2019

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.

Spring 2019

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.

Spring 2019

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 

https://www.nature.com/articles/s41467-019-08750-9


Spring 2019

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.

Winter 2018-2019

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.

https://www.ncbi.nlm.nih.gov/pubmed/30559253

Fall 2018

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.

Schedule (PDF)

http://www.ntsconference.com/schedule/

Fall 2018

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.

https://abstractsonline.com/pp8/#!/4649/presentation/22516

Summer 2018

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.

https://www.cell.com/current-biology/fulltext/S0960-9822(18)30908-4

Discussion of the paper from Thilo Womelsdorf and Kari Hoffman

Spring 2018

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.  

Spring 2018

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.

http://www.apsebmeeting.org/eb2018/session.cfm?id=543

Spring 2017

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.

http://www.apsebmeeting.org/eb2018/session.cfm?id=543

Spring 2017

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...]

Winter 20016-2017

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...]

Fall 2016

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]

Spring 2016

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

Winter 2015-2016

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

Fall 2015

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]