Comment on use of transcutaneous trigeminal nerve stimulation for PTSD

Exploring non-pharmacologic means to treat PTSD will always  get a thumbs up from me.  The results of a recent Clinical Trial exploring the use of transcutaneous trigeminal nerve stimulation was just published in the journal Neuromodulation: Technology at the Neural Interface. Study results were modest but what is most intriguing is how stimulating the trigeminal nerve would have a positive effect on PTSD and also, from previous studies, positive effects on reducing the frequency of epileptic seizures.

Monarch™ eTNS™

Looking at the Neurosigma website, the company who's product the Monarch™ eTNS™ is behind this research, they point out that the trigeminal nerve is the largest cranial nerve.  Yes it is considered by some
criteria to be "the largest" but the vagus nerve is the longest cranial nerve and by far the most complex.  The vagus nerve supplies vital organs, is the primary parasympathetic nerve, plays a vital role in our immune system, and helps to control systemic inflammation.

Also, they do not call the superficial stimulation of the trigeminal nerve with the Monarch transcutaneous stimulation but refer to it as external stimulation.  I'm wondering if that is for marketing purposes.  Why purchase a Monarch if a similar function can be served by a transcutaneous nerve stimulator?

As to how the trigeminal nerve, a nerve whose primary function is for sensory and motor functions in the face and mouth regions, can have such systemic effects on complex disorders such as PTSD and epilepsy, the answer may come from tracing the path of the trigeminal nerve. The nucleus tractus solitarius, located in the dorsomedial medulla, does receive a few projections from the trigeminal nerve.  The Neurosigma website points this out.  They also state the involvement of the locus coeruleus in the proposed mechanism for the effects of trigeminal nerve stimulation. Again, there are some connections. The vagus nerve supplies dense connections to the these structures, not just a few fibers.

Regarding the proposed involvement of the locus coeruleus in the etiology of trigeminal nerve stimulation, therapy, recent research has shown that the antidepressant effects of vagus nerve stimulation (VNS) is via the locus coeruleus (LC).  Here are some highlights of that study (Journal of Psychiatric Research Sep 2015):

• VNS has an antidepressant-like effect in the forced swim test.
• Lesioning the LC abolishes this antidepressant-like effect of VNS.
• Our results support a key role for the LC in the antidepressant mechanism of VNS.
• The results of this study demonstrate that the noradrenergic neurons from the LC play an important role in the antidepressant-like effect of VNS. 

Just last week (Feb 16, 2016) a new study has added a key piece to the Alzheimer's puzzle by demonstrating the locus coeruleus to be 'ground zero' in the etiology of Alzheimer's:

Researchers highlight brain region as 'ground zero' of Alzheimer's disease
The locus coeruleus is a small, bluish part of the brainstem that releases norepinephrine, the neurotransmitter responsible for regulating heart rate, attention, memory, and cognition. Its cells, or neurons, send branch-like axons throughout much of the brain and help regulate blood vessel activity. Its high interconnectedness may make it more susceptible to the effects of toxins and infections compared to other brain regions, said lead author Mara Mather.

Mather, Professor of Gerontology and Psychology at the University of Southern California Leonard Davis School of Gerontology, added that the locus coeruleus is the first brain region to show tau pathology—the slow-spreading tangles of protein that can later become telltale signs of Alzheimer's disease. Though not everyone will get Alzheimer's, autopsy results indicate that most people have some initial indications of tau pathology in the locus coeruleus by early adulthood, she added. Trends in Cognitive Sciences March 2016

It appears to me to be quite clear that transcutaneous vagus nerve stimulation (see previous post) could play a key role in protection from Alzheimer's disease and there is a new Clinical Trial starting very soon to test that hypothesis. Details from the Clinical Trial:
There are three aims in this project:

1. To investigate how the functional interaction between the locus coeruleus and other brain areas, in particular the medial temporal lobe areas, during memory processes (encoding, consolidation and retrieval) change with development of Alzheimer's disease.
2. To investigate associations between noradrenaline, memory performance and brain functioning. The investigators aim to investigate how acute noradrenalin levels change during the different memory processes and whether or not this is beneficial for performance. Furthermore, the investigators will investigate whether this interaction between noradrenalin, memory performance and brain functioning is different healthy older individuals (n =35) or patients with prodromal Alzheimer's disease (n =35).
3. To investigate the underlying neural network changes during transcutaneous vagus nerve stimulation. The investigators will focus on differences in functional connectivity between the locus coeruleus and the medial temporal lobe areas in healthy older individuals and prodromal Alzheimer's disease patients. An experimental condition will be compared with a sham condition in a pseudo-randomized cross-over design.

After some initial excitement regarding the potential of trigeminal nerve stimulation, it appears as though stimulating the trigeminal nerve is just acting as a middleman to achieve the same or better effects that can be achieved using vagus nerve stimulation.  Neurosigma does state "The NTS is a key regulator of the parasympathetic, or “rest and digest” nervous system, and provides a direct connection between the trigeminal and vagus nerve systems." So lets just cut out the BS and go for the gold.

This is not a technology I would invest in.  Best bet, in my opinion, cut out the middleman and go right to the source - stimulate the vagus nerve to treat PTSD.  DARPA, the Defense Advanced Research Project Agency has been funding research on vagus nerve stimulation to treat PTSD. DARPA's research appears to focus on the vagus nerve with no mention of the trigeminal nerve. As for a potential new Clinical Trial, perhaps stimulating the auricular branch of the vagus nerve and the trigeminal nerve simultaneously would provide some sort of synergist effect as opposed to just stimulating the vagus nerve.

Bindi and Third Eye

Another possible explanation for the positive effects of transcutaneous trigeminal nerve stimulation is it's effect on the "third eye" as the locations on the forehead are the same..  The "third eye" is a mystical concept that turns out to have real evolutionary significance. There are some 'primitive' extant reptiles such as the Tuatara which has a parietal eye that in 'higher' vertebrates became the pineal gland. The FDA approved Cefaly for migraines appears to be capitalizing on this concept by its design. Dimethyltryptamine (DMT) has been shown to be produced by the mammalian pineal gland. Interesting!

The Cefaly trigeminal nerve stimulator for migraines - Third Eye?

Transcendental Meditation for treating PTSD

A new article in Military Medicine (Jan 2016) details research performed by military medical personnel at Dwight David Eisenhower Army Medical Center's Traumatic Brain Injury Clinic at Fort Gordon, Georgia. 74 active-duty service members with PTSD or anxiety disorder were divided into experimental and control groups with both receiving treatment as usual and the experimental group also receiving training in and practice of Transcendental Meditation (TM).  The experimental group receiving the extra TM training and practice were able to "reduce or even eliminate their psychotropic medication and get better control of their often-debilitating symptoms."

While I applaud their approach and the willingness of military personnel to undertake such timely research, I do have a few issues with their work.  First, it appears the control group did not receive an equal amount of extra staff attention and were not assigned a task that would also take an equal amount of time daily to do something akin to just sitting quietly for 20 minutes twice a day.  This was not a properly controlled study and does little to show anything special about TM.

Not that there isn't anything special about TM, it is just that this study design fails to show it. What David Lynch is doing with the Operation Warrior Wellness (OWW) program is highly commendable. Maharishi Mahesh Yogi's efforts to spread the practice of meditation globally should have won him the Nobel Peace Prize and his book Maharishi Mahesh Yogi on the Bhagavad-Gita : A New Translation and Commentary, Chapters 1-6 was a classic.  It is unfortunate he did not have time to translate the last 12 chapters. According to TM, the key is to 'be without the three gunas'. Being without the three gunas is, in essence, a state of non-judgemental mindfulness.

Still, I'm not convinced that TM has any special edge over other meditation techniques.  This is not a competition.  Comparing gurus is one step in the direction of cutting off someone's head because they do not believe what you believe. Just getting more people to meditate and quiet their sympathetic nervous system and default mode network would be a major step forward towards saving humanity from our possible path of self-destruction.

EMWave2

If these researchers want to be on the cutting edge of research in this field, there are at least two additional steps they can take. First they can supplement the effectiveness of participants meditation progress using heart rate variability biofeedback (HRV-b).  Having instant feedback on how you are progressing is extremely valuable. Increasing heart rate variability through biofeedback has been shown to improve the balance between the parasympathetic and sympathetic nervous system. There is a relatively inexpensive unit, the EMWave2 available from HeartMath that has been utilized in many studies to include some by the military.

My personal experience with the EMwave2 has been positive.  It's cost is not prohibitive ($200 dollars) although its durability can be improved.  My units tend to peter-out after about 1 year of fairly constant use. The best aspect of this form of non-intrusive biofeedback is its ability to keep you in a state of mindfulness.  When I find my mind wandering, the EMWave2 informs me which makes it a great adjunct to meditation.

I'm not sure if the EMWave2 uses a linear or non-linear algorithm to monitor heart rate variability (they will not divulge this information). The output it provides lets you know when the parasympathetic and sympathetic nervous systems are in balance and is referred to as coherence.

Vagus nerve in green

Electrical stimulation of the auricular branch of the vagus nerve has been shown to decrease sympathetic nerve activity, to increase vagal tone, and to activate the cholinergic anti-inflammatory pathway. The ear is the only place the vagus nerve is superficial and able to be stimulated non-invasively. The increase in vagal tone is achieved without the use of medication and is non-invasive. Decreasing systemic inflammation via the cholinergic anti-inflammatory pathway and increasing vagal tone have shown positive results for treating depression, chronic pain, PTSD, cancer, atrial fibrillation, stroke, heart failure, rheumatoid arthritis to mention a few. The cholinergic anti-inflammatory pathway is a recently described, vital part of the immune system who's role in various disease states is only recently being ascertained.

Vagus nerve stimulation
 with
TENS electrodes

Electrical stimulation of the auricular branch of the vagus nerve has great potential to play a key role in treating many diseases of modern society, it can modulate the default mode network, and that it can be manipulated without drugs is a big plus. What is so amazing is very few physicians have an interest in this process even though it involves a key part of our immune system.  I guess when some drug company comes out with a drug they can write a prescription for then they will start showing some interest.

DARPA, the Defense Advanced Research Project Agency, inventors of the internet (sorry Al Gore) and the premier agency for United States military research, has been funding research on vagus nerve stimulation to treat PTSD. From their website Work Begins to Support Self-Healing of Body and Mind:

"A team at the University of Texas, Dallas, led by Robert Rennaker and Michael Kilgard, will examine the use of vagal nerve stimulation to induce neural plasticity for the treatment of post-traumatic stress. As envisioned, stimulation could enhance learned behavioral responses that reduce fear and anxiety when presented with traumatic cues. Dr. Rennaker is a U.S. Marine Corps veteran who served in Liberia, Kuwait and Yugoslavia."

Not a recommendation but this product found on Amazon may serve the purpose of stimulating the auricular branch of the vagus nerve.

New article from Biological Psychiatry (Feb 2016) from Harvard, Medical College of Wisconsin, and China titled Transcutaneous Vagus Nerve Stimulation Modulates Default Mode Network in Major Depressive Disorder involves stimulation of the auricular branch of the vagus nerve to treat depression and demonstrates its effect on the default mode network.

There is new research involving activation of the locus coeruleus via transcutaneous vagus nerve stimulation and it role in prevention of Alzheimer's.  See details in the next post.

Quiet the Default Mode Network and save the world

It has been demonstrated with fMRI that mindfulness meditation and psilocybin (a must read) both decrease activity in the default mode network and both can promote the experience of oneness, a sense of timelessness, a profound sense of sacredness, and can result in an overall decrease in anxiety. These are qualities that are lacking in the present efforts to deal effectively with global issues of terrorism, climate change, and extreme political polarization.

A new article in the journal Cerebral Cortex used fMRIs to measure brain activities in 3 different cultural groups (Chinese, American and Iranian) while they were reacting to narratives that involved core, protected beliefs. Researchers found increased activity in the “default mode network” when these core, protected values were contemplated.

A press release from the University of Southern California details key aspects of the study.  The press release concludes:

It’s not yet clear whether a value either is or is not protected, or whether the sacredness of a value is on a sliding scale. But in a nation where political beliefs are growing more polarized and entrenched, it’s important to understand what biological processes lie at the root of these values, Kaplan said.

“People will often hold political values as protected values and protected values are at the root of many political conflicts around the world, which is why they’re interesting to us,” he said.

Just a reminder, taking psilocybin is not a game.  It must be done for the right reasons and with proper supervision.  Set and Setting are key.

This one has a very chaotic, out of control default mode network and would not be good for world peace.  He also can not spell and has difficulty with complex issues which limits him to derogatory, grade school level one liners. These characteristics remind me of a former President except this one is not as genial.  Early Alzheimer's?

This gentleman has a very quiet default mode network which is reflected in his face, in his eyes.  He does not take himself too seriously and his ego is not an obstacle to world peace.  Yoda's eyes were patterned after Einstein's eyes.