NeuroSigma Inc. is sharing clinical trial results that will help investigators better understand the therapeutic benefits of eTNS.

Published in Neuromodulation: Technology at the Neural Interface, the study (“Oxygen-15 Labeled Positron Emission Tomography During External Trigeminal Nerve Stimulation”) is the first to report the real-time effects on brain activity among patients undergoing eTNS. The small trial was conducted by a UCLA research team that included Dr. Christopher DeGiorgio, professor and vice chairman of the UCLA Department of Neurology; and Dr. Ian Cook, Professor Emeritus in the UCLA Departments of Psychiatry and Biobehavioral Sciences and of Bioengineering.

“Publication of these results represents a significant milestone for eTNS as this therapeutic modality enters the mainstream,” Dr. Cook said. “An improved understanding of the eTNS mechanisms of action will allow clinicians to better tailor the treatment to individual patients and develop new therapeutic indications.”

The study included five adults, each receiving a series of six PET brain scans. PET is a neuroimaging technique that detects regional brain activity by measuring cerebral blood flow changes. For all six scans, an eTNS device was applied to the test subject—three with eTNS turned on for 60 seconds, and three with eTNS turned off for 60 seconds. Investigators then pooled and analyzed the data to look for significant differences in blood flow between the on and off scans. Results show a two-part mechanism of action where some brain regions exhibited increased activity while others showed decreased activity during eTNS.

“These findings increase our understanding of the mechanism of action of eTNS for multiple neurological and psychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD), depression, and epilepsy. Activations of the medial frontal lobe and cingulate gyrus indicate a potential mechanism for the improvements in attention and mood reported in clinical trials and create a roadmap for future applications in cognitive and behavioral neuroscience,” Dr. DeGiorgio stated. “In contrast, the areas of deactivation support a mechanism for the anti-seizure effect of eTNS because decreased brain activity was observed in regions typically associated with the spread of seizures.”

NeuroSigma’s Monarch eTNS System is a U.S. Food and Drug Administration (FDA)-cleared device for treating pediatric ADHD in the United States. The eTNS technology stimulates the trigeminal nerve, a key pathway that influences brain function, mood, and attention.

“Publication of these important findings is timely as NeuroSigma is preparing to launch the second-generation Monarch eTNS System in the United States in early 2026,” NeuroSigma President/CEO Dr. Colin Kealey said. “The PET biomarker data generated by Dr. Cook and Dr. DeGiorigo complement previous EEG findings in children with ADHD and will help guide clinicians as they add the Monarch device to their clinical practice.”

NeuroSigma is a Los Angeles-based bioelectronic medical device company developing technologies to transform medical practice and patients’ lives. The company’s lead product is the Monarch eTNS System, the first non-drug treatment for pediatric ADHD cleared by the FDA. Pipeline indications for the Monarch eTNS System include neurodevelopmental disorders such as autism spectrum disorder (ASD), learning disabilities, and epilepsy. NeuroSigma has received Breakthrough Device Designation for the Monarch eTNS System from the FDA in drug-resistant epilepsy.