Stimulating Cranial Nerves to Treat Depression

Written by Hannah Siddiqi

Neurophysiology is the investigation of function in the central and peripheral nervous system and it’s a field that has seen a boom in recent decades, as advancements in technology and scientific understanding have further elucidated the function of various nerves within the human body. One such nerve, the vagus nerve, is one of twelve cranial nerves that branch out from the brain, and it is the longest and most complex of the cranial nerves. Its role in human functioning has been known for a while; it is responsible for the regulation of internal organ functions, such as digestion, heart rate, and respiratory rate, among others. However, what’s really interesting is that an innovative treatment that stimulates the vagus nerve has shown promising results in treating major depressive disorders (Hein et al., 2013; Rong et al., 2016).


Previously in conventional vagus nerve stimulation, a device is implanted under the skin and connected to the left vagus nerve via a wire. When activated, the device sends electrical signals along the left vagus nerve to the brainstem. More recently, a non-invasive vagus nerve stimulation device has been developed, which does not require surgical implantation. This is known as transcutaneous vagus nerve stimulation (tVNS).


In 2017, a research study by Fang et al. used tVNS to treat 38 participants with depression. The participants were trained to apply the stimulator themselves at home via ear clips. Stimulation would increase gradually to the greatest point that the participant could tolerate without discomfort. This stimulation would last about 30 minutes and was administered twice a day, at least 5 days a week for a month. To get a standard measure of depression each participant completed the Hamilton Depression Rating Scale (HAM-D) at the start and end of their 4-week treatment course. Furthermore, while various preliminary studies have indicated the efficacy of vagus nerve stimulation for treating depression, the neural mechanism by which the effect on depression might be achieved has not yet been fully investigated. For this reason, the researchers also measured tVNS-induced changes in the brain using fMRI. In order to provide the crucial link showing the association between activation during tVNS stimulation and clinical outcomes, the researchers compared the measures of depression and patterns of fMRI between one group who received the tVSN, and a sham treatment group (the active control group), who were trained to apply their apparatus to a location on the outer ear that is devoid of vagus nerve distribution (Peuker & Filler, 2002). 

Diagram from Fang et al. (2017) of tVNS placement in treatment vs sham conditions

The results are really quite interesting; they showed that the tVNS group displayed significant fMRI signal increases in the left anterior insula (a hub for emotional and saliency processing), which is considered a key region in major depressive disorder neuropathology. Moreover, the insula activation level in the tVNS group was associated with clinical improvement at the end of the 4-week treatment, as indicated by the HAM-D score, when compared to the sham treatment condition. In other words, as insula activation levels increase, depression decreases.


This study is not without its limitations; while there was a significant difference in both behavioural (HAM-D) and imaging (fMRI) results between the tVNS and sham treatment, there was also a significant therapeutic effect of the sham treatment, and this needs further investigation (Fang et al. suggest that the improvements observed following the sham treatment may be attributable to a placebo response). Nevertheless, this study presents tentative evidence supporting the use of tVNS as an effective treatment for depression, and should be commended for investigating the mechanism of change i.e. what’s causing the improvements in clinical outcome.

References:

Fang, J., Egorova, N., Rong, P., Liu, J., Hong, Y., Fan, Y., … & Xu, C. (2017). Early cortical biomarkers of longitudinal transcutaneous vagus nerve stimulation treatment success in depression. NeuroImage: Clinical, 14, 105-111.

Hein, E., Nowak, M., Kiess, O., Biermann, T., Bayerlein, K., Kornhuber, J., Kraus, T. (2013). Auricular transcutaneous electrical nerve stimulation in depressed patients: a randomized controlled pilot study. Journal of Neural Transmission, 120(5), 821-827.

Rong, P., Liu, J., Wang, L., Liu, R., Fang, J., Zhao, J., … & Ben, H. (2016). Effect of transcutaneous auricular vagus nerve stimulation on major depressive disorder: a nonrandomized controlled pilot study. Journal of Affective Disorders, 195, 172-179.