Today's article comes from the Frontiers in Neurology journal. The authors are Ament et al., from Cherry Creek Neurology, in Colorado. In this paper they're exploring the efficacy of a new treatment for mild TBIs (traumatic brain injuries).
DOI: 10.3389/fneur.2025.1642034
There's a decent chance that you or a loved one has suffered a concussion at some point. About a third of all people do. Maybe you played football in high school, or took a tumble on your bike, or got in a bad car accident. Most of the time, it's not a big deal. You're fine after a few weeks.
But...what happens if the story doesn't end there? What happens when the dizziness, the headaches, the brain fog, and the depression stretch on for months or even years?
This, unfortunately, is the reality for a substantial portion of the people who experience what we call a mild TBI (a traumatic brain injury). Their initial scans look normal, and their doctors assure them they're "fine," but as time goes on they're left grappling with symptoms that make it hard to work, hard to think, or hard to just get through the day. Until recently, treatment options for these kinds of symptoms have been frustratingly limited.
But now there's a new piece of tech, a treatment, that's starting to get attention in this space. It's not a drug, it's not invasive surgery, and it's not a brain implant. It's something called non-invasive vagus nerve stimulation, and today we're looking at a study that tested whether or not it actually works. Before we dive into the study itself, let's talk about what's actually happening internally when someone gets a concussion and their symptoms last and last.
When your brain gets jostled around inside your skull, the immediate physical damage is actually just the beginning of the story. This can be followed by a cascade of secondary injury mechanisms that can persist long after the initial trauma. One of the key players is neuroinflammation. This is when your brain's immune system, trying to help, actually ends up making things worse. It releases inflammatory molecules that interfere with normal brain function and can cause progressive damage to your neural networks.
This is where the vagus nerve comes into the picture. The vagus nerve is like your body's built-in anti-inflammatory highway. It runs from your brainstem down through your neck and into your chest and abdomen, carrying signals that help regulate everything from your heart rate to your digestive system. And when you stimulate the vagus nerve, it activates what researchers call the "cholinergic anti-inflammatory pathway." This pathway can suppress the release of the inflammatory molecules and help restore balance to your brain's chemistry. You see, when you stimulate the vagus nerve in your neck, it sends signals up to the brainstem control centers that normally regulate arousal, attention, and stress responses. These are exactly the brain regions that get thrown out of whack after a concussion. The stimulation also triggers a cascade of anti-inflammatory signals throughout your body, helping to calm down the immune system's overreaction.
Now, vagus nerve stimulation isn't new. Surgically implanted vagus nerve stimulators have been used for years to treat epilepsy and depression. But cutting someone open to install a device is a pretty big ask, especially for people who are already dealing with the aftermath of brain injury. That's where non-invasive vagus nerve stimulation comes in. Instead of surgery, you get a handheld device that you place against your neck, right over where the vagus nerve runs close to the surface. Turn it on, and it delivers electrical pulses that can activate the same beneficial pathways without any of the surgical risks.
So far (prior to today's paper) the lab models proved effective and the animal studies have been promising. But models and animal studies can only tell you so much. So the question is:
What happens when you try this in real humans with real persistent symptoms?
That's exactly what the researchers in this study set out to find out. Let's see what they did, how they collected and analyzed the data, and the results they found.
The participants were mostly male, middle-aged adults who had been struggling with persistent symptoms for an average of about six months. This was a real-world clinical population. People who had been prescribed vagus nerve stimulation for symptoms that wouldn't go away.
The researchers used something called the Neurobehavioral Symptom Inventory to gauge how the patients were doing. This is a questionnaire that covers post-concussion complaints across four main categories.
Each symptom gets rated on a scale from zero to four, with four being the most severe.
At the start of treatment, these patients were struggling significantly. Their most severe symptoms were headaches, which averaged close to a three out of four in severity. Fatigue, forgetfulness, difficulty concentrating, and feeling easily overwhelmed all scored well above the midpoint of the scale. That's all to say: these weren't people with mild complaints; they were dealing with significant, life-altering symptoms across multiple domains of brain function.
For treatment, patients received a device that generates a waveform. That waveform mimics the natural patterns of nerve activity. Patients were trained to position the device over their neck near where you can feel your pulse, right where the vagus nerve runs closest to the skin surface. The key to effective treatment is getting the stimulation intensity just right. Too little, and you won't activate the nerve. Too much, and it becomes uncomfortable or could stimulate other nearby structures. The sweet spot is when patients feel a slight pulling sensation or twitch in their lip on the same side. This is actually a reliable sign that you're hitting the vagus nerve at the right strength because that nerve controls some of the muscles in your face. They were instructed to use the device multiple times daily, morning and evening, plus whenever they felt symptomatic. They also received daily reminders and follow-up appointments to troubleshoot any issues with technique or device settings.
Compliance (with the treatment) wasn't perfect, but it was reasonable. On average, patients used the device about sixty percent of the recommended days. Believe it or not that's actually pretty good for a home-use medical device, especially one that requires multiple daily sessions. After about four months of treatment, they re-ran the questionnaire and tabulated the results. Here's what they found:
Out of twenty-two different symptom domains, sixteen showed statistically significant improvement. And the biggest improvements were exactly where you'd hope to see them. Post-traumatic headaches dropped substantially, as did difficulty concentrating. Dizziness decreased, and depression showed marked improvement. They also saw the needle move on nausea, difficulty falling asleep, irritability, and feeling easily-overwhelmed.
When you look at broader symptom categories, the patterns become even clearer.
The four symptoms that didn't reach statistical significance were mostly related to sensory functions: problems with vision, hearing, numbness or tingling, and altered taste or smell. Interestingly, these tend to be more peripherally mediated symptoms, which makes sense given that the treatment is primarily targeting central nervous system inflammation and regulation.
All that being said: statistical significance is one thing, clinical significance is another. So the authors needed to evaluate whether these improvements actually mattered. In other words, they needed a threshold. For this, they defined "responders" as people who experienced at least a thirty percent reduction in symptom severity.
By this measure, the results were still impressive. Nearly half of patients were "responders" for headaches. Similar proportions responded for dizziness, loss of balance, and difficulty falling asleep. More than a third showed meaningful improvement in concentration difficulties and depression. Most importantly, over ninety percent of patients responded to at least one symptom, and about a third met response criteria for at least half of all the symptoms measured. That's broad, meaningful relief across multiple domains of functioning.
And interestingly, it didn't seem to matter how long patients had been suffering before starting treatment. You might expect that people with chronic, long-standing symptoms would be harder to help. But when the researchers divided patients into groups based on how long it had been since their injury, they found no significant differences in either how severe their symptoms were at the start or how much they improved with treatment. This challenges the traditional view that there's a narrow window of opportunity for post-concussion interventions. It suggests that once symptoms become persistent, they may stabilize at a certain level regardless of time since injury, and interventions can still be effective even when deployed well into the chronic phase. From a practical standpoint, this means that even if someone has been told "you just have to learn to live with it" or "it's been too long, there's nothing we can do," treatment might still help.
And from a safety perspective, the treatment appeared to be remarkably benign. No device-related adverse events were reported during the entire treatment period. The worst thing that typically happens is some mild skin irritation at the application site, and even that's uncommon.
Now, the study wasn't perfect of course. To get meaningful results at scale we'll need to see followup studies with control groups, and double-blinds, more objective measurements of symptoms and less reliance on self-reporting. But this study is certainly a good start, and can hopefully help justify funding and running the kinds of studies that need to come next.
If you want to see a detailed breakdown of the composite symptom scores, explore the correlation analyses, learn about the specific contraindications for treatment, or read about the broader implications for post-concussion care delivery, then I'd highly recommend downloading the full paper. The authors provide quite a lot of supplementary data and they discuss considerations around patient selection, and treatment optimization.