Non-Invasive Technique for Recording Involuntary Nervous System Could Warn of Impending Sepsis

The vagus nerve is a “superhighway” of the involuntary nervous system, with tendrils stretching from the skull’s base throughout the torso and abdomen, impacting digestion, heart rate, and immune response. It is crucial in the body's inflammatory reactions to injuries or infections and is a key research subject in life-threatening conditions like sepsis and post-traumatic stress disorder. Now, for the first time, a wearable, non-invasive device has been shown to measure human cervical nerve activity in clinical environments, providing healthcare professionals with a real-time, clinically validated method to observe activity levels in the involuntary nervous system.

The device developed by a research team led by University of California - San Diego (La Jolla, CA, USA) utilizes a sophisticated technique called "magnetoneurography," offering a non-surgical alternative to microelectrodes for monitoring the vagus nerve by accurately and non-invasively detecting cervical nerve activity in real-time. It records what has been termed as Autonomic Neurography (ANG), neural activity from the human vagus and carotid sinus nerves as well as other autonomic nerves found in the skin and muscle of the neck. The technology identifies magnetic fields generated by activity in the vagus and carotid sinus nerves, which alert the involuntary nervous system to potential threats. In their study published July 29, 2024 in Nature Communications Biology, the researchers tested the device on nine adult participants, initially measuring their blood for baseline cytokine levels—proteins that trigger inflammation.

Participants were then exposed to lipopolysaccharides, bacterial toxins that induce a state similar to an inflammatory response from a blood infection. Using the device’s sensors, placed beneath the right ear and over the right carotid artery, the researchers monitored heart rate and magnetic fields from nerve activity. Within 30 minutes post-injection, the device recorded nerve activity changes under the right ear. Blood samples confirmed these changes alongside variations in heart rates, showing correlations with the inflammatory cytokine TNF-α and the anti-inflammatory IL-10. High TNF-α levels are indicative of an elevated risk for septic shock, where an excessive inflammatory response can lead to death. Conversely, high IL-10 levels may suggest a risk of immunoparalysis, where immune cells fail to combat infections, leading to severe consequences.

The researchers identified separate patient groups based on their reaction to the injection, with some displaying higher inflammatory protein levels and more pronounced side effects. This technology might allow doctors to identify patients at increased risk of severe immune responses or immunoparalysis, contributing to sepsis-related deaths. It could also help assess the effectiveness of anti-inflammatory treatments, enhance understanding of the nervous system’s role in PTSD, and adjust therapies targeting the nervous system to suit individual patient needs.

“We are encouraged by our results. The device is poised to provide an early diagnostic marker of pathogen infection, or inflammation from a pathological process,” said the study’s senior author Imanuel Lerman, head of the Lerman Lab of UC San Diego’s Qualcomm Institute, School of Medicine.

“With sepsis, every minute counts and early treatments save lives,” said Troy Bu, a Ph.D. candidate in the Jacobs School’s Department of Electrical and Computer Engineering and the study’s first author. “Early sepsis detection is critical as, every hour sepsis is not treated, the likelihood of death increases by up to seven percent. Our technology can provide doctors with an early warning sign of hyperimmune or immunoparalysis response in sepsis. Doctors can then provide the correct treatment as quickly as possible.”

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