Bioelectric Neuromodulation: Vagus Nerve Stimulation
Vagus nerve stimulation (VNS) is a form of bioelectric neuromodulation, a way of stimulating the brain to regulate neurophysiology. We’re getting rewarding results using vagus nerve stimulation across a range of conditions, including major depressive disorder. The idea has been around for some decades. In 2005 the FDA approved the invasive form of vagus nerve stimulation as a treatment for depression.
In the past vagus nerve stimulation had always required surgery. Then, in 2002, anatomists made some intriguing discoveries about the distribution of the vagus nerve and found branches in the ears. As a result, nowadays we can now affix an electrode to a specific region of your ear and in that way stimulate the vagus nerve. It’s that simple—no pain, no significant adverse side effects, and, especially, no surgery.
What is the Vagus Nerve?
It is the 10th cranial nerve. Cranial nerves are the nerves that connect some part of your body to your brain. The vagus nerve connects your brain to your gut and is responsible for gut-brain communication. You have probably seen something about the importance of your microbiome, all the little microbes that live in your gut and make such an important contribution to your health. The vagus nerve is the nerve that is responsible for the primary communication between your brain and your gastrointestinal tract, your gut. In fact, it also connects your brain to your heart, your lungs, and many other internal organs.
Why should vagus nerve stimulation help with depression?
It is a long and complex answer, so we’ll not go into every detail here. There is good scientific evidence to show the benefits of vagus nerve stimulation on depression. There are a few reasons for why vagus nerve stimulation makes such a positive difference to depression.
Vagus Nerve Stimulation and Inflammation
There is a growing awareness that psychological stress and unhappiness cause changes in your immune system (which fights disease) and in your endocrine system (hormones). In turn, those changes are responsible for alterations in the functioning of your nervous system that result in depression. We have learnt that there is an association between depression and inflammation. Tellingly, nowadays we sometimes treat depression with antihistamines. Clearly, there is a strong link between depression and inflammation.
Your body produces a lot of cortisol, a stress hormone, in response to chronic stress and depression. Elevated production of cortisol causes inflammation. Remarkably, it turns out that vagus nerve stimulation reduces inflammation in a major way. We’ve learnt that this is via activation of the cholinergic anti-inflammatory pathway (CAP).
Vagus Nerve Stimulation and Neuroplasticity
Depression is not simply a “chemical imbalance.” It involves measurable changes in brain networks—especially those that regulate mood, motivation, reward, and emotional balance. Brain imaging studies show altered activity in frontal regions, the anterior cingulate cortex, and limbic structures such as the amygdala in people with major depressive disorder.
Vagus nerve stimulation influences these same networks. When we stimulate the vagus nerve, signals travel upward to the brainstem (particularly to the nucleus tractus solitarius), and from there to widespread regions involved in emotional regulation. This bottom-up input can shift the balance of activity in mood circuits that have become stuck in maladaptive patterns.
Over time, this appears to promote neuroplasticity—the brain’s ability to reorganise itself. Research suggests that VNS can increase levels of brain-derived neurotrophic factor (BDNF), a molecule that supports neuronal growth and synaptic strengthening. In practical terms, this means the brain becomes more capable of forming healthier patterns of activity rather than remaining trapped in rigid, depressive states.
Hippocampal Health, Depression, and Long-Term Brain Function
Chronic or recurrent depression does not only affect how you feel—it is associated with measurable changes in brain structure. One of the most important regions involved is the hippocampus. This structure plays a central role in memory, learning, and emotional regulation. It is also highly sensitive to stress.
In people with long-standing depression, the hippocampus is often smaller than expected. This is thought to reflect the cumulative effects of stress hormones, inflammation, and reduced neuroplasticity over time.
This matters because the hippocampus is also critically involved in conditions such as Alzheimer’s disease and other forms of cognitive decline. Depression is therefore not only a disorder of mood—it is also associated with long-term brain health risks. The exact relationship is complex, but changes in hippocampal integrity are likely part of the link.
This is where emerging findings around vagus nerve stimulation are particularly interesting. In a small MRI study of patients with treatment-resistant depression, those who improved with VNS also showed increases in hippocampal volume over time. Of course, these findings are preliminary and need to be interpreted with caution. They do not mean that VNS reverses structural changes or prevents dementia.
The study demonstrated increases in hippocampal volume consistent with a reversal of atrophy in this small sample. However, these findings are preliminary and require replication in larger studies before firm conclusions can be drawn. This research does suggest that effective treatment—particularly when it supports neuroplasticity and regulation—may also influence the brain systems that underlie resilience, memory, and adaptation.
From a clinical perspective, this reinforces an important idea:
Treating depression effectively is not only about improving mood in the present. It may also be about protecting and supporting brain function over time. The brain remains plastic, even in chronic illness, and regulation-focused interventions can move it in the right direction.
Vagus Nerve Stimulation and Autonomic Regulation
Depression is frequently associated with autonomic imbalance. Many people with depression show reduced vagal tone and reduced heart rate variability (HRV), which are markers of diminished parasympathetic (rest-and-digest) regulation. When the parasympathetic system is underactive, the body remains biased toward a stress response.
Transcutaneous vagus nerve stimulation can help restore this balance. By increasing parasympathetic signalling, VNS can improve heart rate variability, reduce physiological stress reactivity, and support a calmer internal state. This physiological shift often translates into improved mood, better sleep, and enhanced emotional resilience.
In other words, we are not merely trying to “boost mood.” We are helping the nervous system return to a more regulated state. From that more stable platform, psychological therapies, behavioural changes, and lifestyle interventions tend to work better.
A Regulation-First Approach
At Ormond Neuroscience, we view depression fundamentally as a disorder of regulation. Emotional regulation, stress regulation, inflammatory regulation, and network regulation are all intertwined. Vagus nerve stimulation fits naturally into this framework because it works at the level of core physiological regulation.
It is not a magic bullet, nor does it replace psychotherapy, medication when appropriate, exercise, sleep optimisation, or nutritional strategies. But as a safe, non-invasive, and biologically grounded intervention, it offers a powerful adjunct to comprehensive care.
If you would like to know whether vagus nerve stimulation might be appropriate for you or a loved one struggling with depression, feel free to get in touch. We are happy to discuss how this form of bioelectric neuromodulation fits into a broader, science-based treatment plan.
