A research group has demonstrated that a wearable, non-invasive device can assess activity in the cervical nerves of humans within clinical environments. This development could assist healthcare providers in customizing treatments for inflammatory ailments like sepsis and PTSD.
A research team from UC San Diego has made a groundbreaking achievement: they have successfully shown that a wearable, non-invasive device can measure human cervical nerve activity in clinical environments for the first time.
The device captures what the researchers refer to as Autonomic Neurography (ANG), which includes neural activity from the vagus and carotid sinus nerves, alongside other autonomic nerves located in the skin and muscles of the neck. The vagus nerve serves as a major pathway in the involuntary nervous system, extending from the base of the skull down through the torso and abdomen to regulate digestion, heart rate, and the immune response. It plays a critical role in how the body responds to inflammation caused by injury or infection and is a focal point for studies on life-threatening illnesses like sepsis, which claims the lives of at least 1.7 million adults in the U.S. annually, according to the National Institute of General Medical Sciences, and post-traumatic stress disorder (PTSD), which affects approximately 3.5% of the population according to the National Institute of Mental Health.
To provide healthcare providers with a real-time, clinically validated tool for measuring activity levels in the involuntary nervous system—an early indicator of bodily stress—the researchers created a flexible, adhesive-integrated electrode array (as detailed in a 2022 Scientific Reports article). The current research, published on July 29, 2024, in Nature Communications Biology, utilized this method to identify deep neural activity in a simulated hyperinflammatory clinical model.
“We are excited by our findings. This device is set to deliver an early diagnostic indicator of infection or inflammation due to pathological processes,” commented Imanuel Lerman, the study’s senior author and head of the Lerman Lab at UC San Diego’s Qualcomm Institute, School of Medicine, and Jacobs School of Engineering, as well as the VA Center of Excellence for Stress and Mental Health. Lerman, who established InflammaSense Inc., the company behind the device’s technology, added, “Based on our findings, we are now rolling out the device in the intensive care units of the Jacobs Medical Center at UC San Diego Health to detect early neural signaling that may signal an onset of sepsis.”
Troy Bu, a Ph.D. candidate in the Jacobs School’s Department of Electrical and Computer Engineering, served as the primary author of the study.
Real-Time Monitoring in the Emergency Room
The novel device aims to substitute surgically implanted microelectrodes for monitoring or stimulating the vagus nerve. It utilizes an advanced technique called “magnetoneurography,” enabling accurate, non-invasive, real-time detection of cervical nerve activity. The device senses the magnetic fields generated by the activity in the vagus and carotid sinus nerves, which “pulse” to alert the involuntary nervous system to potential threats.
In their tests, researchers involved nine adult human participants. Blood samples were taken from patients to measure baseline levels of inflammation-related proteins known as cytokines. Subsequently, they received injections of lipopolysaccharides, toxins derived from bacteria, which temporarily induced a hyperinflammatory response similar to that seen in blood infection cases.
In a magnetically isolated room at the UC San Diego Qualcomm Institute Magnetoencephalography Center, the researchers positioned their device’s sensors near the vagus nerve below the right ear and over the right carotid artery, areas where both the vagus nerve and carotid sinus nerve are located. The device tracked heart rate and the magnetic fields produced by nerve activity.
Within half an hour of the lipopolysaccharide injection, the device noticed shifts in nerve activity below the right ear. Researchers validated the increased nerve activity and the secretion of inflammatory proteins through blood analyses. They also monitored heart rate variations, observing a clear connection between nerve firing at both locations and fluctuations in specific inflammatory cytokines, including tumor necrosis alpha (TNF-α) and the anti-inflammatory cytokine IL-10.
High levels of TNF-α can indicate a higher risk for patients of developing septic shock, a severe condition where the body’s inflammatory response goes awry and leads to critical systemic damage that can ultimately result in death.
In contrast, elevated levels of IL-10 may signal patients who are at risk of immunoparalysis—a state occurring during sepsis when immune cells are rendered unable to combat either external pathogens or resident viruses, which can result in uncontrollable infections and death.
“In sepsis, timely intervention is crucial, as each minute counts and rapid treatment can save lives,” remarked Bu. “Early detection of sepsis is essential; for every hour that treatment is delayed, the risk of death increases by as much as seven percent. Our technology can offer physicians early indicators of either hyperimmune or immunoparalytic responses in sepsis, allowing for swift and appropriate treatment.”
Similar to findings from the 2022 study, researchers again identified that patients fell into groups with distinct reactions to the stress from the injection. Some participants exhibited more significant peaks in inflammatory proteins and pronounced side effects, while others showed lower peaks.
With this innovative technology, doctors might be able to discern subgroups of patients who are particularly susceptible to heightened immune responses and immunoparalysis, which both play a role in complications and fatalities related to sepsis. Additionally, the device could aid in gauging the effectiveness of treatments aimed at reducing inflammation, enhancing our understanding of the nervous system and inflammation among individuals affected by PTSD and related mental health issues, and personalizing therapy dosages tailored to each patient’s nervous system needs.
This study was a collaborative effort involving UC San Diego, Sandia National Laboratories, the University of Wisconsin-Madison, the VA Center for Stress and Mental Health, Quspin Laboratory, Stanford University, and InflammaSense Inc.
Funding support came from the Biomedical Advanced Research and Development Authority (BARDA) and the David and Janice Katz Neural Sensor Research Fund in Memory of Allen E. Wolf.
