At the Translational Neurophysiology lab, we use neurostimulation as a means to study the nervous system and to treat disorders in which the nervous system is affected or implicated.
We use methods from neuroscience, autonomic, cardiovascular and metabolic physiology, neuroanatomy and neural engineering to study the neural circuits and mechanisms of autonomic control in health and disease, to interface neural recording and stimulation devices with the nervous system, and to deliver targeted, responsive and adaptive neuromodulation therapies to treat disorders of the nervous system, heart and vessels, metabolism and other organ systems.
A major focus of the lab is the vagus nerve. The vagus mediates a big part of the bidirectional communication between the brain and peripheral organs and systems. It has been implicated in several diseases, from epilepsy and depression, to rheumatoid arthritis and inflammatory bowel disease. Consequently, stimulation of the vagus nerve (VNS) is currently explored as a therapeutic option in those and many other diseases like hypertension, renal diseases, obesity, diabetes, atherosclerosis, heart failure, arrhythmias, neurodegenerative diseases, pain, etc. At the TNP lab, we develop methods and techniques to interface with, stimulate and record from the vagus, aiming to investigate neural circuits of which it is part and the mechanisms by which it monitors and controls physiological functions, to understand its role in the pathogenesis and pathophysiology of diseases, and to develop VNS-based therapies to treat those diseases.
Technologies, techniques and implants for nerve stimulation and recording
We design electrode geometries, optimize modes of electrical stimulation and develop techniques for surgical implantation of neural probes to deliver targeted energy to the nervous system in a temporally-, spatially- and cell-specific manner. In collaboration with engineers at the Institute of Bioelectronic Medicine (IBeM), we take part in the development of neural probes for recording activity from and delivering stimulation to neural tissue. By leveraging biophysical principles of neurostimulation, we design and in vivo test electrical stimulation waveforms that target different fiber populations of the vagus nerve to maximize desired and minimize undesired effects of VNS. Finally, we develop surgical implantation methodologies in small and large animal models that allow us to chronically interface recording and stimulation devices with the vagus nerve.
Extraction of evoked compound nerve action potentials from vagus nerve recordings (IEEE EMBC Proc 2019)
An implant for long-term vagus nerve stimulation in mice (BioArxiv 2020)
Neural circuits and mechanisms for autonomic control
We study the neural circuits and physiological mechanisms by which the nervous system informs the brain about the status of peripheral organs and systems, and exerts autonomic control over them. We use anatomical techniques, including histology, immunohistochemistry and viral tracing, to map the neural circuits subserving these functions and to study how these circuits are altered by disease. We use methods from organ physiology, neurophysiology, optical physiology and genetics to understand neural activity related to autonomic function in nerves, ganglia and the brain and to study how nerve stimulation affects the brain and the organs to which the nerves project. We focus on autonomic circuits affecting the function of the heart and lung, vascular tone, and metabolism.
We develop in vivo paradigms for controlling neural activity-dependent synaptic plasticity in the nervous system. These paradigms rely on detection of neural and physiological activity with appropriate probes and hardware, and contingent delivery of activity-dependent neurostimulation in real time. Plasticity is induced by directly stimulating the cells that are synaptically-connected, or by delivering neuromodulators to those cells, either pharmacologically or electrically, e.g. by VNS. We wantg to use these paradigms to control neural plasticity and "re-sculpt" the circuits that have undergone maladaptive changes in neurological, metabolic and cardiovascular disorders.
Targeted, responsive & adaptive neuromodulation
We develop techniques and technologies for targeted, responsive and adaptive neuromodulation of central and peripheral neural systems. "Targeted" means stimulation is delivered with the aim of affecting specific fiber types, physiological functions or organs. "Responsive" means that neurostimulation is delivered upon the occurrence of certain physiological events or states of the system or the organism. "Adaptive" means that neurostimulation is optimized in real time with regards to its physiological and/or neurological effects, by adjusting its parameters on the fly to maximize effectiveness and minimize side effects. We use special surgical methods, probes and stimulation techniques to selectively activate organ systems, nerves and nerve fibers. We develop and deploy recording and stimulation systems, both rack-mounted and implantable, to interface with the nervous system in real time, in a bidirectional manner.
Anodal block permits directional vagus nerve stimulation (Sci Rep 2020)
Closed-loop neuromodulation in physiological and translational research (Cold Spring Harb Perspect Med 2018)
Integrated bioelectronic therapies
We test neurostimulation-based, bioelectronic therapies in preclinical and translational models of disease. We develop and study diseases in small and large animal models, each of which has unique advantages and limitations in the translation process. We design our experiments so that what we learn from earlier models is directly transferable to later models, and ultimately to human clinical applications. Such therapies are tested in clinical trials, in collaboration with clinical teams at Northwell Health.
Pulmonary arterial hypertension: the case for a bioelectronic treatment (Bioelectron Med 2019)
Noninvasive sub-organ ultrasound stimulation for targeted neuromodulation (Nature Comm 2018)