Topics

Non-Invasive Bioelectronic Analytics

2019-09-27 06:30:44 | BioPortfolio

Summary

Biomarkers can be evaluated to provide information about disease presence or intensity and treatment efficacy. By recording these biomarkers through noninvasive clinical techniques, it is possible to gain information about the autonomic nervous system (ANS), which involuntarily regulates and adapts organ systems in the body. Machine learning and signal processing methods have made it possible to quantify the behavior of the ANS by statistically analyzing recorded signals. This work will aim to systematically measure ANS function by multiple modalities and use decoding algorithms to derive an index that reflects overall ANS function and/or balance in healthy able-bodied individuals. Additionally, this study will determine how transcutaneous auricular vagus nerve stimulation (taVNS), a noninvasive method of stimulating the vagus nerve without surgery, affects the ANS function. Data from this research will enable the possibility of detecting early and significant changes in ANS from "normal" homeostasis to diagnose disease onset and assess severity to improve treatment protocols.

Description

Biomarkers that reflect disease presence or intensity, or treatment efficacy are central to medical advancements. Recorded biomarkers provide information about physiological processes regulated by the autonomic nervous system (ANS), which include blood pressure, heart rate, sweating, and body temperature. The ANS has two major divisions: sympathetic and parasympathetic systems. Most organs receive reciprocal input from both systems to achieve homeostasis through ANS balance. This regulation occurs without conscious control (i.e., autonomously). Dysregulation of the ANS can occur as the result of disorders or injuries, including diabetes, sepsis, spinal cord injuries (SCI), Parkinson's disease, and many other conditions.

The ANS is the part of the nervous system that regulates and integrates bodily functions that typically run involuntary, particularly internal organs including blood vessels, lungs, pupils, heart, sweat, and salivary glands. Along with immunological systems, it controls and adapts homeostasis of the internal environment based on changes in the external environment. Disturbances in autonomic regulation have been described in a variety of diseases and disorders, including those that directly affect the nervous system, such as spinal cord injuries and stroke, and those that afflict other organ systems, such as sepsis and infection, rheumatoid arthritis, Crohn's disease, diabetes mellitus, and numerous heart conditions. This dysregulation manifests differently for each of these conditions, even inconsistently across patients, and the significance of symptoms due to ANS dysfunction are not well understood.

The ANS can be divided into two major branches: the sympathetic and parasympathetic systems. All internal organs are innervated by one or both component systems through the ANS main conduits, which include the brainstem, spinal cord, and cranial nerves, such as the vagus nerve. The branches typically function opposite and complementary of each other; physiological changes associated with the sympathetic system include accelerating heart rate, dilating pupils, and perspiration, while the parasympathetic system slows the heart, lowers blood pressure, and relaxes muscles. Both systems work in tandem to modulate and maintain blood pressure, vagal tone, heart rate, respiration, and cardiac contractility. While both systems operate to maintain homeostasis, the sympathetic system can be considered a quick response and mobilizing system, while the parasympathetic is a more slowly activated and dampening system.

Instead of measuring the ANS directly from the central or peripheral nervous system through invasive implants, it is possible to record physiological signals through advances in noninvasive clinical testing. Laboratories are able to test autonomic function and rely on batteries of accepted, noninvasive tests. According to the American Academy of Neurology (AAN), standard techniques of autonomic testing include measuring heart rate and blood pressure variability during deep breathing, tilt table, and the Valsalva maneuver to assess cardiovagal (parasympathetic) and sudomotor (sympathetic) function. It is straightforward to add to the limited necessary equipment (blood pressure cuff, electrocardiogram [ECG]) by including electroencephalography (EEG) to measure brain activity, electromyography (EMG) to measure muscle activity, and eye tracking glasses to measure pupillometry during this battery. All noninvasive signals can be measured during controlled perturbations to characterize the ANS. Assessment of ANS function is now used in multiple disciplines, including neurology, cardiology, psychology, psychophysiology, obstetrics, anesthesiology, and psychiatry.

Neural reflexes control responses in the cardiovascular, pulmonary, gastrointestinal, renal, hepatic, and endocrine systems. The vagus nerve-based inflammatory reflex is of particularly interest at the Feinstein Institute for Medical Research and has been shown to regulate immune function. The nervous system interacts with the immune system by this pathway; molecular mediators of innate immunity activate afferent signals in the vagus nerve to the brainstem, which sends efferent signals down the vagus nerve to regulate inflammation and cytokine release. Vagus nerve stimulation (VNS) has been shown to decrease production and release of pro-inflammatory cytokines; bioelectronic devices have been used in preclinical and pilot clinical trials to reduce inflammation in patients with rheumatoid arthritis and Crohn's disease.

The auricular branch of the vagus nerve comes from the vagus and innervates cutaneous areas of the outer ear. Transcutaneous auricular vagus nerve stimulation (taVNS) offers a non-invasive means of stimulating the vagus nerve without surgical intervention. The device consists of a clip that supplies electrical signals to processes of the auricle, and it has been used in previous clinical studies for multiple conditions, including refractory epilepsy, depression, pre-diabetes, tinnitus, memory, stroke, oromotor dysfunction, and rheumatoid arthritis, with additional studies planned for therapy or treatment of stroke, atrial fibrillation, and heart failure. These studies have used a range of electrical stimulation settings and sites; the mechanism of taVNS and responses are not well understood, as well as the effects of changes in stimulation parameters on ANS.

Recently, application of machine learning models and decoding algorithms permits utilizing commonly used clinical measurement of physiological signals to better understand broader phenomena of autonomic function and dysregulation. Research has been focused on developing quantitative standards based on biomarkers to aid with diagnosis, prognosis, and estimates of treatment efficacy. Autonomic data could potentially capture objective measures of disease states, and machine learning techniques can be used to extract relevant features towards building a predictive model of ANS balance. By training such a model on recordings from healthy, able-bodied individuals, the investigators plan to characterize ANS balance, and then apply this model to new data sets and individuals to diagnose or predict disease states.

Modern methods of computational science have been used to decode complex clinical and experimental data by detecting patterns, classifying signals, and extracting information towards new knowledge. Through signal processing techniques, it has been possible to decode autonomic nervous system signals conveyed through the vagus nerve by identifying groups of vagal neurons that fire in response to the administration of specific cytokines. Additionally, machine learning has been used to quantify clinical pain using multimodal autonomic metrics and neuroimaging, and large-scale ambulatory data has been used to monitor physiological signals and develop multi-sensor models to detect stress in daily life.

Additionally, the investigators want to examine how these measurements are affected by the use of non-invasive transcutaneous electrical stimulation of the vagus nerve. Stimulation of the vagus nerve by a surgically implanted stimulator regulates and suppresses pro-inflammatory cytokine release. This has now been used in a successful clinical trial to treat rheumatoid arthritis and Crohn's disease. Non-invasive transcutaneous stimulation of the vagus nerve has also been showing promising early results, indicating that non-invasive methods of activating a specific part of the autonomic nervous system can be used successfully to treat disease. However, real-time biomarkers of efficacy of this treatment are not available.

Here, the study will develop a framework to decode a multitude of noninvasive physiological signals during controlled autonomic testing to form a model that can quantify ANS balance, as well as the effects of taVNS on the system, in healthy and able-bodied individuals. Data derived from this study will enable the ability to detect early and significant deviations from "normal" homeostasis and provide novel non-invasive real-time biomarkers that could be used to assess disease onset or severity, as well as efficacy of a therapy in activating the ANS in a specific way. In the long-term, this will improve current treatment protocols and suggest new therapeutic opportunities.

Study Design

Conditions

Autonomic Dysfunction

Intervention

Standing-Squatting-Standing Test, Deep Breathing Test, Cold Pressor Test, Cold Face Test, Valsalva Maneuver, Transcutaneous Auricular Vagus Nerve Stimulation (taVNS)

Location

The Feinstein Institutes for Medical Research
Manhasset
New York
United States
11030

Status

Recruiting

Source

Northwell Health

Results (where available)

View Results

Links

Published on BioPortfolio: 2019-09-27T06:30:44-0400

Clinical Trials [4088 Associated Clinical Trials listed on BioPortfolio]

The Effects of Prolonged Standing Compared to Prolonged Sitting on Postprandial Lipemia

The effects of 12 hours of prolonged standing will be compared to prolonged standing on a high fat tolerance test the following day. Plasma triglycerides, insulin, and glucose will be meas...

Cognitive and Motor Benefits of Standing

Upright-working has been proven to benefit health by combating the negative effects of physical inactivity. However, long-term commitment to static standing regimens may be limited due to ...

Arm Training in Standing After Stroke

This study will examine the feasibility of providing task-oriented arm training in standing or during walking in individuals with movement deficits due to stroke. Participants will receive...

The Effects of Standing Tutorials on Problem-Based Learning (PBL) Among Undergraduate Students

Problem-based learning (PBL) is an education model utilized by Maastricht University and many other universities worldwide. PBL occurs in small, collaborative tutorials, under the facilita...

Cross-over Study of Three Modular Devices for Aid in Patient Standing and Transfer

The main objective of this study is to evaluate via a physiological analysis of the movements involved in standing, the level of forward flexion of the spine (in cm on the horizontal axis)...

PubMed Articles [12069 Associated PubMed Articles listed on BioPortfolio]

Influence of Pulmonary Ventilation Rate and Breathing Cycle Period on the Risk of Cross Infection.

This study examined the characteristics of the exhaled airflow pattern and breathing cycle period of human subjects and evaluated the influence of pulmonary ventilation rate and breathing cycle period...

Is Bilateral Deficit in Handgrip Strength Associated With Performance in Specific Judo Tasks?

Turnes, T, Silva, BA, Kons, RL, and Detanico, D. Is bilateral deficit in handgrip strength associated with performance in specific judo tasks? J Strength Cond Res XX(X): 000-000, 2019-The aim of this ...

Standing postural stability during galvanic vestibular stimulation is associated with the motor function of the hemiplegic lower extremity post-stroke.

: The vestibular system is profoundly involved in standing postural stability. Patients with post-stroke hemiparesis have poor postural control function; nevertheless, it is unclear as to how the vest...

Chronic Standing Desk Use and Arterial Stiffness.

Sedentary activity and sitting for at least 10 hours per day can increase the risk for cardiovascular disease by more than 60%. Use of standing desks may decrease sedentary time and improve cardiovasc...

Sex-specific effects of sitting vs standing on upper body muscle activity during text typing.

Standing computer work is increasingly popular. However, despite the higher rates of computer work-related disorders in women, no studies have compared how standing work affects men and women. Twelve ...

Medical and Biotech [MESH] Definitions

Tests of accuracy in pronouncing speech sounds, e.g., Iowa Pressure Articulation Test, Deep Test of Articulation, Templin-Darley Tests of Articulation, Goldman-Fristoe Test of Articulation, Screening Speech Articulation Test, Arizona Articulation Proficiency Scale.

A projective test used to evaluate a broad range of personality variables including pathology of thought and perception. The subject's responses to inkblot prints are scored along with subjective interpretation by the test administrator.

A significant drop in BLOOD PRESSURE after assuming a standing position. Orthostatic hypotension is a finding, and defined as a 20-mm Hg decrease in systolic pressure or a 10-mm Hg decrease in diastolic pressure 3 minutes after the person has risen from supine to standing. Symptoms generally include DIZZINESS, blurred vision, and SYNCOPE.

A test to determine the lowest sound intensity level at which fifty percent or more of the spondaic test words (words of two syllables having equal stress) are repeated correctly.

Method of measuring the bactericidal activity contained in a patient's serum as a result of antimicrobial therapy. It is used to monitor the therapy in BACTERIAL ENDOCARDITIS; OSTEOMYELITIS and other serious bacterial infections. As commonly performed, the test is a variation of the broth dilution test. This test needs to be distinguished from testing of the naturally occurring BLOOD BACTERICIDAL ACTIVITY.

More From BioPortfolio on "Non-Invasive Bioelectronic Analytics"

Quick Search

Relevant Topics

Surgical treatments
Surgery is a technology consisting of a physical intervention on tissues. All forms of surgery are considered invasive procedures; so-called "noninvasive surgery" usually refers to an excision that does not penetrate the structure being exci...

Cardiology
Cardiology is a specialty of internal medicine.  Cardiac electrophysiology : Study of the electrical properties and conduction diseases of the heart. Echocardiography : The use of ultrasound to study the mechanical function/physics of the h...


Searches Linking to this Trial