A wearable optical device that records activity in the autonomic nervous system could provide medical professionals with a tool for detecting early signs of physical stress. The device is based on ventral cervical magnetoneurography (vcMNG), a method that uses magnetic field sensors to trace and visualize neural activity along peripheral nerves and identify cervical nerve firing noninvasively in real time. The device detects the magnetic fields arising from activity in the vagus and carotid sinus nerves, as well as other autonomic nerves found in the skin and muscle of the neck. These nerves influence digestion, heart rate, and the immune system, and play a crucial role in the body’s inflammatory response to injury or infections like sepsis. The vcMNG-based tool, which was developed and tested at the University of California, San Diego (UC San Diego), could enhance understanding and management of the neuroimmune axis and help guide treatment based on an individual’s distinct endophenotype. Researchers from UC San Diego and colleagues introduced a noninvasive device for recording activity in the human cervical nerves. Courtesy of Qualcomm Institute/UC San Diego. The device uses optically pumped magnetometers (OPMs) to record ventral cervical activity derived from vcMNG. Ventral cervical OPMs are an emerging class of quantum magnetic sensors that can detect changes in cortical and peripheral neuronal currents with a sensitivity of one foot per square root of hertz (1 ft/√Hz). The team modified the OPMs to extend their bandwidth up to 500 Hz at a sensitivity of 20 ft/√Hz. Each OPM sensor contains a glass vapor cell with rubidium atoms enclosed in it. The glass vapor cell receives circularly polarized laser light directed by a prism toward a photodetector to monitor the light intensity transmitted through the vapor cell. When the background magnetic field is equal to zero, the circularly polarized laser light spin polarizes the rubidium atoms in the direction of the light beam, making the atoms transparent to the incoming light. A magnetic field in the direction perpendicular to the light path causes the atoms to absorb light. The photodetector identifies the change in transparency and measures voltage as a function of the external magnetic field. The researchers tested the device in nine healthy human adults. They injected the subjects with bacteria-sourced toxins called lipopolysaccharides, inducing a temporary hyperinflammatory state in the subjects that mimicked the inflammation associated with a blood infection. They placed sensors beneath the subjects’ right ear and over the right carotid artery, where both the vagus nerve and carotid sinus nerve are found. The device monitored heart rate and the magnetic fields arising from nerve activity, recording the activity with OPM sensors that were adhesively attached to the body. (Left) Subjects received lipopolysaccharide injections to induce temporary hyperinflammation, mimicking a blood infection. (Middle) Small, noninvasive devices called optically pumped magnetometers (OPMs) recorded autonomic neurography activity from neural structures (right vagus nerve, right nodose ganglion, and right carotid sinus nerve) in the human neck in response to the perceived inflammation. (Right) Neural signals categorized subjects’ inflammatory responses to lipopolysaccharide injections as high or low, providing a real-time, wearable bioindicator of inflammation in humans. Courtesy of UC San Diego. Within half an hour of the injection with lipopolysaccharides, the device detected changes in the subjects’ nerve activity. The researchers confirmed the increase in nerve activity and the release of inflammatory proteins through blood samples. They also recorded changes in heart rate, as well as a link between nerve firing at both sites and changes in an inflammatory cytokine called tumor necrosis alpha (TNF-α) and the anti-inflammatory cytokine called IL-10. Patients with high levels of TNF-α are at a higher risk of entering septic shock. Elevated levels of IL-10 can indicate a risk of immunoparalysis. “Our technology can provide doctors with an early warning sign of hyperimmune or immunoparalysis response in sepsis,” said researcher Troy Bu. “Doctors can then provide the correct treatment as quickly as possible.” The researchers further found that, as in a previous study, some subgroups showed higher peaks in the presence of inflammatory proteins and stronger side effects than other subgroups. The vcMNG technology could make it possible for doctors to identify subgroups of patients that have a higher risk of a hyperactive immune response and immunoparalysis. It could also be used to determine whether treatments are reducing inflammation in the body, to better understand the nervous system in people experiencing posttraumatic stress disorder and other mental health conditions, and to tailor therapies to individual patients’ nervous systems. “The device is poised to provide an early diagnostic marker of pathogen infection, or inflammation from a pathological process,” said Imanuel Lerman, a professor of electrical engineering and anesthesiology at UC San Diego. “The device will detect early involuntary neural signaling indicative of impending sepsis.” Lerman, who is the founder of InflammaSense Inc., the company that licenses the technology, said that the device is now being used at the intensive care units of the Jacobs Medical Center at UC San Diego Health. The research was published in Nature Communications Biology (www.doi.org/10.1038/s42003-024-06435-8).
