Friday, 16 December 2011

Vagus Nerve Stimulation (VNS) & Transcutaneous Vagus Nerve Stimulation (tVNS)

The vagus nerve is the 10th cranial nerve originating in the medulla and innervates various regions of the human body from the inner ear to the cardiovascular and digestive systems. The vagus nerve is therefore appropriately named after the Latin word for ‘wanderer’. It is no surprise that the vagus nerve is one of the largest cranial nerves, in comparison to the olfactory nerve which is relatively small.
Vagus Nerve Stimulation (VNS) is the broad term used to describe stimulation of the nerve fibre mainly through electrical impulses. There are three main ways of stimulating the vagus nerve;
1. Surgical Implant – A small electrical implant, similar to a pace maker is implanted into the patient’s chest. Electrodes from the device are wrapped around the vagus nerve (See Figure 1) with the control panel being left outside the body so the patient is free to control the frequency and strength of the pulses.

2. Transcutaneous VNS (tVNS) tVNS is the process of stimulating the nerve fibre externally through the skin rather than through internal surgery. This can be accomplished by placing an electrode on various sites of the pinna of the outer ear including the tragus, anti-tragus, helix and lobule.
3. Vagal Manoeuvres ­­(VM)- A VM is a physical act which due to the wide spread connections of the vagus nerve can cause stimulation throughout the body. An example of a VM is ‘Valsalva’s manoeuvre’ in which the patient is asked to bear down as if to have a bowel movement whilst holding their breath and hold this position for up to 30 seconds.
Each method of VNS has strengths and limitations. The surgical approach to VNS has the obvious weakness of surgical risk which includes surgery and post surgery complications and/or infections. It may also have a greater chance of re-implantation due to post-surgical malfunction or complication. Ben-Menachem (2001) reported that approximately 3-6% of implant surgery led to post-surgery infection – using this data and the knowledge that over 17,000 patients have had VNS implant surgery (Schachter & Schmidt, 2003) we can see that approximately 500-1000 people may have had a post-surgical infection.
VNS involving a surgical implant has been reported to have a greater risk of side effects such as transient hoarseness, transient parasthesia and transient dyspnoea (Uthman et al, 2004).
Another large risk from vagus nerve surgery is that accidental severing of the nerve will lead to problems with swallowing, paralysis of the vocal cords and would interrupt efferent communication from various organs (Tortora & Anagnostakos, 1987).
Transcutaneous stimulation offers various benefits to implant VNS in that there is no need for surgery. This automatically takes away the risk of surgical or post-surgical infections. The risk of re-admission to surgery due to malfunction is also null. tVNS currently has no known or reported side effects.
VNS is the most widely adopted treatment for drug-resistant epilepsy (Schachter & Schmidt, 2003) so it is no surprise that most of the research around VNS has large clinical and therapeutic applications. Only recently has VNS been applied to various other aspects of human cognition, such as memory. I will now discuss past and present research and then move on to discuss research which is currently in the planning stages.
In 2004 Uthman et al published a 12 year observational study investigating the long term effects of VNS on 48 patients with epilepsy. The results showed that mean seizures decreased by 26% after 1 year, 30% after 5 years and 52% after 12 years.
This study also found something else out which was rather curious; Lower current output from the device was sufficient to cause sufficient stimulation. This suggests that if a patient does not respond to low current VNS then they will not respond to VNS at all, this has also been backed up by previous research investigating VNS uses on epilepsy by Salinsky et al in 1996.
This research also showed that VNS does not cause tolerance over time; this was apparent as seizure frequency continued to decrease over time and did not level out.
VNS has also proved useful when it comes to treating treatment-resistant depression. Schlaepfer et al (2007) ran a clinical study using 74 treatment-resistant depression patients. Using psychometrics it was discovered that the use of VNS reduced severity of depression with efficacy increasing over time.
A study investigating the effects of VNS on eating behaviour has reported that VNS can alter cravings. Bodenlos et al (2007) reported using tVNS matched with images of food that participants cravings before and after the experimenter were significantly different. What is quite interesting about this study is that the craving differences were found to be specific to sweet foods. It was also noted that having the VNS device set to different amplitudes dictated the craving variability.
VNS has also proven useful and very effective as an added treatment for coronary artery disease. Zamotrinsky et al (2001) used VNS alongside surgical interventions on people suffering coronary artery disease with severe angina symptoms. The group of patients who received VNS pre-surgery had a heart failure rate of 12% compared to the control group which had a heart failure rate of 90%.
One particular study which has put the vagus nerve into the spotlight is a study by Engineer et al (2011). Using a rat model of tinnitus, the research group was able to design a treatment for tinnitus in rats. This was accomplished by using VNS at the same time as matching tones.
The implications of the above study are transforming the treatment approaches to tinnitus in Humans. In August 2011, Cerbomed – the group originally responsible for VNS put up an advert to recruit human participants in the same study as above. The difference this time is that it will be completed with external tVNS.
The research landscape as detailed above seems to portray VNS as a wonder treatment, but is anyone sure how it works? The short answer is no. The longer answer is that there are probably various different mechanisms of action due to the nerves widespread connections and functions through both the motor and sensory systems.
Engineer et al (2011) postulates that VNS causes a transient neuro-plastic effect allowing for a greater re-structuring ability during a task. However this is most certainly only applicable for research into tinnitus.
The positive results from Engineer et al (2011) beg the question; can we use VNS when trying to learn a new task?
A study was recently in the news for cutting learning time in half through direct transcranial stimulation in which prolonged structural changes could be seen (Fields, 2011). This kind of learning stimulation could prove useful if retention holds up for those who have to re-learn vital motor skills such as stroke patients.
Ben-Menachem, E. (2011). Vagus Nerve Stimulation, Side Effects, and Long-Term Safety.. American Clinical Neurophysiology Society, 18(5), 415-418.
Bodenlos, J. S., Kose, S., Borckardt, J. J., Nahas, Z., Shaw, D., O'Neil, P. M., & George, M. S. (2007). Vagus nerve stimulation acutel alters food craving in adults with depression. Appetite, 48, 145-153.
Engineer, N. D., Riley, J. R., Seale, J. D., Vrana, W. A., Shetake, J. A., Sudangunta, S. P., . . . Borland, M. S. (2011). Reversing pathological neural activity using targeted plasticity. Nature, 470, 101-106.
Fields, R. D. (2011, November 25). Amping Up Brain Function: Transcranial Stimulation Shows Promise in Speeding Up Learning. Scientific American. Retrieved December 16, 2011, from
Salinsky, M. C., Uthman, B. M., Ristanovic, R. K., Wernicke, J. F., & Tarver, W. B. (1996). Vagus nerve stimulation for the treatment of medically intractable seizures.. Neurology, 53, 1176-1180.
Schachter, S. C., & Schmidt, D. (2003). Introduction. In Vagus Nerve Stimulation. (2nd ed.). (p. x). London, United Kingdom: Martin Dunitz.
Schlaepfer, T. E., Frick, C., Zobel, A., Maier, W., Bajbouj, M., O'Keane, V., . . . Corcoran, C. (2007). Vagus nerve stimulation for depression: efficacy and safety in a European study. Psychological Medicine, 1-11.
Tortora, G. J., & Anagnostakos, N. P. (1987). Cranial Nerves. In Principles of anatomy & physiology. (5th ed.). New York, United States: Harper & Row.
Uthman, B. M., Reichl, A. M., Dean, J. C., Eisenschenk, S., Gilmore, R., Reid, S., . . . Roper, S. N. (2004). Effectiveness of vagus nerve stimulation in epilepsy patients: A 12 year observation. Neurology, 63, 1124-1126.
Zamotrinsky, A. V., Kondratiev, B., & Jong, J. W. (2001). Vagal neurostimulation in patients with coronary artery disease. Autonomic Neuroscience, 88, 109-116.

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