4) transcutaneous Vagus Nerve Stimulation (tVNS)
is a very new and exciting treatment for medical and psychiatric conditions.
In 1997 the FDA approved the surgical implantation of a vagus nerve stimulator for the treatment of Seizures (epilepsy). Then for depression in 2005 and for weight loss in 2015. (Information about surgical vagus nerve stimulation is below. We do a non-surgical method but much can be learned from the older procedure.)
Because a small specific area of skin on the outer ear is innervated by the vagus nerve, gentle stimulation of that skin has been found to produce similar brain activation (Kraus 2007, Dietrich 2008) as the surgical implant.
In Europe two tVNS devices have been approved for use - for Epilepsy (seizures) in 2010 and Pain in 2012 (CerboMed-Nemos) and another device for headaches (GammaCore) .
GammaCore is also approved for the acute and prophylactic treatment of primary headaches (cluster headache, migraine, hemicrania continua), and reactive airway disease (asthma, exercise- induced bronchospasm, COPD), as well as adjunctive therapy for epilepsy prevention and reducing the symptoms of certain anxiety/depression conditions (eg, panic disorder, posttraumatic stress disorder, major depressive disorder, obsessive- compulsive disorder), gastric mobility disorders, and irritable bowel syndrome
(Grazzi L, Usai S, Bussone G.. Gammacore device for treatment of migraine attack: 2014:G12.
Gaul C, Diener H, Solbach K, et al.. Non-invasive vagus nerve stimulation using gammacoreVR for prevention and acute treatment of chronic cluster headache: Report from the randomized phase of the preva study; 2014:I7. )
OTHER USES of Transcutaneous Vagus Nerve Stimulation (tVNS):
Although the transcutaneous method has not been not been specifically approved in the United States (i.e. off-label) it is legal and being investigated (and found to be effective and safe) for many conditions including:
Atrial Fibrillation (Stavrakis 2015, Yu 2013)
Depression (Hein 2013, Aaronson 2013)
Dementia (Polak 2006)
Diabetes (Huang 2014, Li 2015)
Endotoxemia (Huston 2007, Schmidt 2008)
Memory (Jacobs 2014 2015)
Myocardial Infarction (Wang 2015)
Chronic Migraine Headache (Straube 2015)
Acute Migraine (Goadsby 2014)
Cluster Headache (Gaul 2014, Nesbitt 2013)
Pain (Laqua 2014, Busch 2013)
Postoperative Cognitive Dysfunction (POCD) (Xiong 2009)
Chronic Pelvic Pain (Napadow 2012)
Tinnitus (Li 2015, Hyvarinen 2015, Kreuzer 2014, Kreuzer 2015)
Schizophrenia (Hasan 2015)
Stroke (Cai 2014)
In our experience, it is most effective for Anxiety (Generalized Anxiety, Panic Disorder, PTSD and Social Anxiety) and Insomnia.
How transcutaneous Vagus Nerve Stimulation Works (Mechanism of Action)
1) stimulating the skin of the ear,
2) stimulates the Auricular Branch of the Vagus Nerve
3) the stimulation goes to a nucleus (cluster of nerve cells) called the Nucleus tractus solitarius
4) the Nucleus tractus solitarius receives information from the body (heart, lungs, intestines, immune system) and
5) sends output to Locus coeruleus and the Dorsal raphe nucleus.
6) Locus Ceruleus is the brain's primary source of norepinephrine (aka noradrenaline)
7) Dorsal Raphe nucleus is the brain's primary source of serotonin
8) so those two structures produce alertness/energy (noradrenaline) and confidence (serotonin)
9) those two then send those chemicals (neurotransmitters) to the whole brain, especially parts for thinking and feeling
(Thalamus, Hippocampus and Amygdala)
• How Does tVNS Work?
1) MORE SEROTONIN (CALM CONFIDENCE) & NOREPINEPHRINE (RELAXED ENERGY) - Stimulating the skin causes sensory nerves to increase activity in the Nucleus Tractus Solitarius (NTS). Then the NTS sends connections to the Locus Coeruleus (which makes norepinephrine, also called noradrenaline). The Locus Coeruleus stmiulates the Dorsal Raphe (which makes serotonin) and the Hippocampus which is a central structure for emotion and memory.
Fig. 6: The vagus nerve sends afferents to the nucleus tractus solitarius (NTS), which in turn projects to the locus coeruleus through disynaptic pathways... Vagus nerve stimulation (VNS) would facilitate the excitatory pathway on neurons in the locus coeruleus more than the inhibitory one. The locus coeruleus would then modify the firing rate of serotonin (5-HT) neurons through its monosynaptic input to the dorsal raphe nucleus. Therefore, VNS is believed to act first on the locus coeruleus, and then indirectly on 5-HT neurons in the dorsal raphe nucleus. It leads to a marked enhancement of norepinephrine (NE) and serotonin (5-HT) transmission. (from Manta 2009 Enhancement of the Function of rat serotonin and norepinephrine neurons by sustained vagus nerve stimulation)
••How Does tVNS Work?
2) BETTER RELATIONSHIP WITH SELF & LESS RUMINATION- Transcutaneous vagus nerve stimulation increases the functional connectivity (the way parts of the brain connect and communicate) of the default mode network (DMN) structures. The DMN is a set of brain areas that are more active when you are not focused on outside things or activities, awake and at rest. The DMN is related to our relationship with ourself, our thoughts about our feelings, and emotion control (Connolly 2013, Berman 2011 & Nejad 2013). People who are depressed have more self-focus and sensitivity to stress (Rodriguez 2012).
3) LESS STRESS MORE RELAXATION - Transcutaneous vagus nerve stimulation improves heart rate variability (Clancy 2014, Leeds, UK), Lower sympathetic (adrenalin, fight or flight), and more parasympathetic (rest, digest, attend and befriend) activity is a predictor of better health in many conditions including heart disease, high blood pressure, sleep apnea and obesity.
The story of modern vagus nerve stimulation, began with Jacob Zabara at the Department of Physiology, Temple University School of Medicine in Philadelphia. He developed and refined the process of surgical vagus nerve stimulation for epilepsy (seizures). The surgically implanted device was FDA approved for seizures in 1997 and depression in 2005. The procedure that we use is not surgical, yet the brain structures which are activated reflect vagus nerve activity.
Transcutaneous vagus nerve stimulation has advantages over surgery
1) Less pain,
2) Less cost
3) More people can benefit from it and
4) More flexible, more possibilities to change the procedure to suit individual people, left, right, front back, low frequency high frequency etc.
5) People with depression get better in one month instead of one year.
Figure 3. Yellow indicates brain regions that showed significant functional connectivity increase with default mode network in the transcutaneous vagus nerve stimulation group as compared with sham transcutaneous vagus nerve stimulation. Blue indicates brain regions whose default mode network functional connectivity changes (posttreatment minus pretreatment) were negatively correlated with the corresponding Hamilton Depression Rating Scale score changes across all subjects. L, left; OPFC, orbital prefrontal cortex; Precu, precuneus; rACC, rostral anterior cingulate cortex. (Fang 2016 transcutaneous vagus nerve stimulation Modulates Default Mode Network in Major Depressive Disorder. )
SURGICAL VAGUS NERVE STIMULATION
(FIGURE 5–1. from Higgins & George 2009 - Brain Stimulation Therapies for Clinicians)
Vagus Nerve Stimulation began as a Surgical Procedure
The Cyberonics Surgically Implanted Vagus Nerve Stimulator, FDA Cleared in 1997.
The VNS generator (A) contains a small battery that generates electrical impulses. A surgeon implants the device under the skin over the chest (B) and attaches the electrodes to the left vagus nerve (C). Regular sig- nals from the VNS device travel up the vagus nerve (D) and ultimately alter activity in the cerebral cortex.
(FIGURE 5–3. from Higgins & George 2009 - Brain Stimulation Therapies for Clinicians)
Information from the Body rises to update the Brain. This informs the part of the brain that regulates Arousal and Emotion.
The sensory fibers of the vagus nerve terminate in the nucleus tractus solitarius (NTS), and the major output of the NTS is to the locus coeruleus (and several other structures such as the raphe nuclei). Projectors from the locus coeruleus to other areas of the brain are believed to mediate some of the effects of VNS. (FIGURE 5–5. from Higgins & George 2009 - Brain Stimulation Therapies for Clinicians)