By the Clinic’s Director, Ashok Gupta
I’m excited to share with you my explanation of these conditions, which I call "Neuro-Immune Conditioned Syndromes (NICS)." I have spent the last twenty years researching and refining this explanation. It is based on my medical paper which was published in a peer-reviewed medical journal in 2002.
The paper was first published online in 2000. Normally this therapy was only available to a relatively small number of patients that I am able to see at my clinic, but now everyone in the world can experience its powerful effects.
Please watch these videos for an explanation of what causes your conditions
I suffered from chronic fatigue syndrome (ME/CFS) myself. Around 20 years ago, I developed it while studying at University.
Since then, I have dedicated my life to finding an effective treatment for ME/CFS and associated conditions such as Fibromyalgia, Multiple Chemical Sensitivities, IBS, Burnout, etc. I have been completely well for many years, and I successfully treat patients globally.
To help you understand the process that I believe has helped me and many others to improve, I will look at:
- An overview of The Amygdala & Insula Hypothesis a ‘vicious cycle’ that, once triggered by severe stressors in people with certain risk factors can perpetuate neurological overstimulation, physiological dysfunction, and many physical symptoms.
- An explanation of major symptoms in the context of this hypothesis.
- A brief summary of Amygdala & Insula Retraining (AIR) concepts – how patients may break the vicious cycle by applying techniques that encourage the amygdala, insula, prefrontal cortex and associated brain structures to discontinue the hypothesized overstimulation.
You can also sign up for the free trial and watch Session 3, which goes through the hypothesis in detail.
THE AMYGDALA & INSULA HYPOTHESIS
My medical research seems to indicate that these conditions are neurological in nature, and may be caused by abnormalities in a brain structure called the ‘amygdala,’ and the ‘insula’.
One of the amygdala’s roles is to protect the body from potential threats.
- Research has traditionally focused on physiological or emotional threats,
- Whereas recent research is showing that the amygdala and insula are involved in protection mechanisms and conditioned immune responses related to chemical and immunological threats as well. See a summary of this novel research here: https://www.guptaprogram.com/wp-content/uploads/2019/03/Learned-Immune-Responses-Schedlowski-Pacheco-Lopez-2010.pdf
This hypothesis serves as a potential unifying model for the various observations in patients. I published my hypothesis in the peer reviewed journal Medical Hypotheses in 2002.
Below, I will go through a basic explanation of the medical paper in layman’s terms using the following diagram:
Genetic and Environmental Risk Factors (1)
Right at the top, let’s start with the predisposing factors to developing these illnesses – i.e., the risk factors. These may include genetic factors and environmental factors yet to be fully determined.
Then there are two other precipitating factors which contribute to these illnesses developing in someone.
Triggers: Acute Psychological Stress (2) & Viral, Bacterial, or Other Triggers (3)
The start of the illness is often accompanied by psychological or physical stress, as well as some kind of acute physical illness.
- In the case of ME/CFS, that physical illness might be a particularly difficult virus or bacterial infection (e.g., Glandular Fever, gut enteroviruses, etc.), or another kind of illness.
- In fibromyalgia, the physical trauma may be an accident, or ongoing chronic pain in a part of the body.
- In MCS, the trigger may be heavy exposure to a toxin.
- In IBS, it may be food poisoning or a similar traumatic event for the gut.
- For other conditions, they relate to the original triggering injury or infection.
There will be crossovers in symptoms between these three conditions, according to the theory. The theory predicts that the pattern of symptoms in the body will be different, but that the underlying cause may be the same. The theory still holds if there is a gradual onset versus a specific onset (see medical paper for further details.)
Gulf War Syndrome may represent a combination of all three illnesses to varying degrees, as at the time there was exposure to immunizations, toxins, and physiological stresses all at the same time.
CONDITIONING IN THE AMYGDALA & INSULA
The combination of these precipitating factors changes the circuitry of the amygdala and the insula, making it continually over-stimulate the body (4).
During the trauma:
- The amygdala learns to be hyper-reactive to any symptoms detected in the body, in association with the ‘insula’ which can no longer process incoming signals and overstimulates the brain and body
- This conditioning happens unconsciously without a person actually realizing it is happening.
CHRONIC STIMULATION OF THE AROUSAL SYSTEM
From then on, the amygdala and insula continually over-stimulates the sympathetic nervous system directly (5)
The sympathetic nervous system is the emergency response of the body to threats. When it is triggered, the parasympathetic nervous system (bodily repair, detoxification, digestion, etc.) is switched off and energy is diverted to the emergency.
- It over-stimulates the hypothalamus and the whole HPA (Hypothalamic-Pituitary- Adrenal) Axis, which subsequently downgrades as a result, making it difficult for the body to respond to stress.
- The amygdala also over-stimulates the whole brain, keeping many brain circuits in a state of hyper-arousal. This adversely affects the levels of neurotransmitters in the brain, including serotonin and dopamine.
- There may also be conditioning in the immune system. This means that aspects of the immune system are inappropriately re-triggered in a unique pattern individual to each patient.
- Finally, this over-stimulation causes higher levels of oxidative stress in the body, and a compromised immune system.
A continual unremitting stimulation can cause symptoms which can severely affect every single organ and system in the body, including the endocrine (hormonal) system, and the immune system. (See the Appendix detailing “How the Different ME/CFS/FMS Symptoms are Created with Continual Amygdala & Insula Stimulation.”)
Furthermore, continual stimulation can cause secondary effects in the body, which then lead researchers to think that those physical observations are the cause of the condition, whereas they are simply symptoms of a deeper underlying brain abnormality.
SYMPTOMS AND SECONDARY ILLNESS CYCLES
Hyper-arousal of the body then causes the symptoms (6) and creates Secondary Illness Cycles (7).
Over-stimulation can cause adaptation in receptors so that systems are down-regulated, or certain systems may simply exhaust due to over-stimulation, as is the case with the adrenal glands. Nitric oxide levels may rise (as per the observations of Professor Martin Pall), which can cause a whole host of secondary effects and symptoms in the body, including mitochondria dysfunction, perpetuating the entire vicious circle. Because the immune system is responding inappropriately, opportunistic viruses such as HHV-6 have the opportunity to flourish, increasing symptoms.
Finally, at 7, secondary illnesses such as allergies and chemical sensitivities can occur due to the hypersensitivity of the entire system.
Sympathetic over-activity means that sleep rhythms are affected, so the restorative “delta” sleep required for bodily repair is not effective. This has also been shown in Post Traumatic Stress Disorder, an illness where the amygdala has also been heavily implicated. This causes a patient to feel unrefreshed the next morning, causing severe exhaustion, and contributing to pain in fibromyalgia.
These symptoms are detected by the sensory thalamus/cortex and the insula cortex – the parts of the brain that receive incoming information from the senses (8).
And to complete the cycle, incoming signals are magnified by the amygdala, which keeps the brain and nervous system in a state of hyper arousal. (9)
* The insula may be involved in interpreting the emotional meaning of the symptoms, and passing that representation on to the amygdala. The Insula also retriggers aspects of the immune system due to the inappropriate conditioning
* At 9, the amygdala is traumatized by any symptoms that it detects in the body, and instantly re-stimulates bodily systems at 4 again.
Note that this central nervous system sensitivity (and resultant abnormal sensory processing causing heightened pain awareness) is gradually becoming a more accepted hypothetical model in fibromyalgia. This then perpetuates into the vicious circle as in the diagram.
FACTORS DETERMINING SYMPTOMS & SEVERITY
If the circle becomes particularly vicious, a patient can become bed-bound. If the cycle is milder, the patient may be able to function to a varying degree. The symptoms in each patient will depend on three factors:
- The severity of the conditioning effects in the amygdala, insula, and associated brain structures.
- The specificity of the conditioning; that is, what symptoms and what reactions were going on in the body at the time of the original trauma.
- The specific timing of the trauma ‘ although symptoms can change over time.
Due to the secondary effects of the condition on the body, food intolerances can develop, as well as general sensitivities. This is because when the brain and body are on high alert, the amygdala (in association with other brain structures) is prone to learning new responses to stimuli it would not normally care about.
When the sympathetic system is aroused, digestive and detoxification systems are turned down or switched off, which may explain why many patients complain of feeling “toxic” inside.
A patient will also find that stress can exacerbate the symptoms – simply because it “speeds up” the vicious circle, and the body does not have sufficient resources to deal with that stress. The stress can be mental, emotional or physical.
With some patients, the conditioning effects are not particularly severe, which is why some patients seem to regain their health through general changes in lifestyle. For others, the conditioning in the brain is severe and causes chronic long term illness.
RETRAINING THE AMYGDALA & INSULA- BASIC CONCEPTS
I wish to emphasize that I believe ME/CFS, fibromyalgia and MCS are real physical conditions, and are in no way psychological. The sensitivity conditioning mainly occurs unconsciously.
As I indicated above, Gulf War Syndrome may represent a combination of all three illnesses to varying degrees, as at the time there was exposure to immunizations, toxins, and physiological stresses all at the same time.
Currently, I do not believe that there are any pharmaceuticals which could target such a specific reaction in the brain. Most pharmaceuticals or supplements target the symptoms rather than the underlying cause. If the conditioning effects are mild, successful treatment of symptoms may bring full recovery, but in the majority of cases, this will probably not occur.
The unconscious brain reaction involved in amygdala and insula dysfunction is not normally under a patient’s control, but I believe that some novel “brain retraining” techniques derived from NLP (Neuro-Linguistic Programming), breathing, meditation techniques, and others, can target the reaction and control the amygdala. The techniques are highly specialized, and do not fit under any one category, which is why I refer to them as “Amygdala & Insula Retraining.”
Luckily the amygdala and insula constantly communicates with other parts of the brain, and that’s where retraining can take place.
In animal models, it is understood that the amygdala can be controlled with new neurons being formed, connecting from the pre-frontal cortex to the amygdala/insula, to subdue and control its reactions. Also strengthening the ability of the insula and anterior cingulate to regulate and inhibit reactivity in the brain (the ‘inhibition mechanisms’)
- Some studies have shown that patients with ME/CFS have lower grey matter volume in this part of the brain (pre-frontal cortex), as well as excessive delta wave activity in the prefrontal cortex
- Other studies have shown that regular meditation can increase the volume of this part of the brain, showing that “brain” exercises can alter the structure of the brain.
Amygdala & Insula Retraining is designed to strengthen the prefrontal cortex and restore inhibitory mechanisms in the insula, anterior cingulate and other associated structures. All the Amygdala & Insula Retraining techniques are now available as an interactive DVD recovery programme. I found that most patients could not afford to come to the clinic for treatment, so I wanted to create something that was affordable and easy to use at home.
APPENDIX – HOW THE SYMPTOMS OF ME/CFS & FIBROMYALGIA ARE CREATED
It covers the range of physical symptoms as well as cognitive and emotional symptoms that those with ME/CFS, fibromyalgia, and associated illnesses may experience – explaining how they may be products of amygdala hyper-sensitization.
As a preface to all this, I do believe that these symptoms are temporary. That is, they are due to systemic functional changes in the body, rather than permanent organic damage. Stopping the amygdala’s hyper-reactions allows the body to trigger the parasympathetic system, meaning the body’s own healing mechanisms can bring it back to balance and homeostasis.
Muscular Fatigue & Pain, Aching Joints & Tender Points
The stress response is sometimes known as the “fight, flight or freeze” response. These responses, including excessive adrenaline, keep the muscles tense, and are only designed to be triggered for minutes at a time.
Relaxed muscles are in a state called tone, which is a state balanced between relaxation and contraction. Prolonged tension in muscles upsets tone and allows the chemicals of fatigue (e.g., lactic acid) to temporarily accumulate and disperse, causing aches and pain. Prolonged tension is initiated and maintained by the stress response, as the muscles are primed for reaction to dangerous stimuli. This is why you may suffer from aching limbs that seem to feel heavy and drag, but there may be nothing actually physically wrong with the muscles.
A few patients have found that magnesium supplements tend to help muscle tension. This is because magnesium acts as a muscle relaxant, and can be found in green leafy vegetables as well.
Exhaustion from Sleep Problems
Several studies have shown that insomniacs cannot get to sleep mainly because they are worrying about something, even if they are very tired. Studies also show that the amygdala is partly responsible for keeping people awake at night due to unconscious stress. ME/CFS/FMS patients have the same problem: Their minds are constantly being bombarded by thoughts telling them that there is an ever present danger that is unresolved, and so they find it difficult to get to or stay asleep.
When a mind and body is tense, sleep is interrupted and fragmented during the night. Studies have shown that interrupted sleep causes further aches and fatigue the next day. Overall, a prolonged stress response causing an interrupted sleep has adverse reactions on the body clock, and indeed some studies have shown a mismatch between temperature rhythms and melatonin secretion in patients. The mismatches in patients have been shown to be very similar to those suffering from stress and sleep deprivation, as well as PTSD.
Furthermore, it is the hypothalamus that regulates sleep rhythms, and it is precisely this brain structure which is being bombarded by signals from the amygdala.
Post-Exertional Malaise, Adverse Reaction to Exercise
Some studies have also shown that patients do not respond correctly to exercise, in terms of inadequate release of a stress hormone called cortisol. This is because the severe stress response means that the stress glands may eventually get depleted (e.g., adrenal exhaustion), or they downgrade and adapt to chronic stress, and while the signals still exist to release cortisol, the response no longer occurs.
Furthermore, the system may have cut back on supplying cortisol, because it has been over-stimulated in the past. Because muscles are already exhausted from being tensed up all day, they also find it difficult to respond to exercise.
There may also be a whole host of hormonal changes in the body which mean that the body cannot respond effectively to physical, mental or emotional stresses.
If the brain and body has been stimulated continually, it cannot perform appropriately because as far as it is concerned, it already has “been performing” for long periods of time, and exhaustion easily sets in.
Digestive Problems, e.g., Irritable Bowel Syndrome (IBS)
The digestive system has its own nervous system, sometimes called the “small brain.” It becomes stimulated by the brain via the autonomic nervous system during stress, and this causes problems in the gut, and may tense muscles and generally over-stimulate the gut.
Also, when the “fight or flight” response is initiated by the sympathetic nervous system, adrenaline and noradrenaline direct the bodily energies and resources to the organs which are involved in fighting or fleeing. These are the muscles, so that they can respond quickly, and the brain, so that the mind can think quickly and concentrate on the source of the danger. Therefore, all other non-essential bodily functions are switched off, such as the digestive system.
This means that food regularly passes through the gut but is not digested correctly, giving the symptoms of IBS. Furthermore, all muscles in the body are tensed, potentially including the muscles within the small and large intestines. The colon normally moves food by moderate contractions or spasms. Muscle tension upsets these rhythms, giving either too many or too few contractions, leading to either diarrhea or constipation, or both.
The gut can become highly sensitized to toxic elements in the diet, or at least foods which may now be perceived as toxic. The body is now in a very sensitized state, and therefore will over-protect itself to survive. Oxidative stress may cause “gut leakage,” triggering sensitivity reactions.
Some patients find that changing their diet seems to help, and that is because there are certain food types which are easier to digest. Eating foods which are difficult to digest while the digestive system is in this state theoretically could worsen symptoms.
Immune System Symptoms, e.g., Sore Throat, Swollen Glands
The immune system is always in a state of delicate balance, ready to respond appropriately to a threat. However, if the perception of that threat is overstated, there may be some aspects of a reactivated immune response that is constantly on alert.
I will not go into the neurobiology of this mechanism here (it is commented upon in the medical paper). Suffice to say that, given that the original trauma often occurs in the presence of a severe virus/bacterial infection, it is no mystery that the body will retrigger immune defenses as a way of making sure the body survives, even if no viral threat exists. This can often feel like having flu or a slight fever, as well as swollen glands and a sore throat, and may be the effects of chemicals called cytokines. This conditioning is likely to be stored in the insula, and retraining targets the insula in persuading it that no further threats are present.
In some patients, this may result in a susceptibility to viral infections, and many of my patients report this. Others, however, may find that they do not have any more viruses than normal.
Latent Virus Reactivation/High Viral Titres
If the immune system is inappropriately retriggered, latent opportunistic viruses can take hold. Furthermore, triggering of the stress system is known to reduce the effectiveness of the immune system, thereby allowing opportunistic viruses to flourish, causing further symptoms. Recently, Professor Garth Nicolson showed that there were similar levels of multiple, systemic bacterial and viral infections in ME/CFS patients as there were in people with autism. Autism is a disorder where sustained amygdala hyperarousal is accepted as a model for partly explaining the disorder.
The delicate muscles which accommodate the lens of the eye are also affected by muscular fatigue, so that vision may be blurred, especially when looking near-to-far and vice versa. Eye fatigue also occurs because, when the fight or flight system is initiated, the vision sharpens and the eyelids retract so that the eyes can focus better on the source of the danger.
Autonomic Dysfunction: e.g., Temperature, Sweating, Blood Pressure Problems
The amygdala and insula send direct signals to the autonomic nervous system, which co-ordinates many bodily responses including temperature and blood pressure. Therefore, abnormalities in autonomic function can be directly attributable to chronic stimulation by the amygdala. Anxiety is well known to cause sweating, and even temperature changes.
Some patients may become “orthostatically intolerant”, e.g., they have low blood pressure when they stand up, as tested by the tilt table test. This may be because of excessive pooling of blood in the legs, as the autonomic nervous system constricts blood vessels in the body, except in the limbs, so that a person can run away from dangers. This may cause problems when standing up, like dizziness, as well as reduced blood flow to the head.
Multiple Chemical Sensitivities
The limbic system of the brain (which houses the amygdala and the hypothalamus) has been implicated in allergic responses and sensitivity responses. These systems become “over-cautious,” reacting to toxins and pathogens “just in case” they represent dangers. When the amygdala and insula are on high alert, it is prone to learning new sensitivities and threats which ordinarily would not have been reacted to.
When the body is in this sympathetic stress mode, non-essential systems are switched off, including aspects of the body’s detoxification and elimination processes, and healing and repair systems. Therefore, if this reaction is prolonged, there may be accumulation of toxins in the body. Many patients complain of “feeling toxic.” If the amygdala is retrained, the parasympathetic system can gradually detoxify the body in the correct way.
Intolerance to alcohol has often been cited as a characteristic marker of ME/CFS/FM. Much medical research demonstrates that alcohol actually induces the stress response by stimulating hormone release via the hypothalamus. This is exactly the response which the amygdala is conditioned to respond to, causing further symptoms. Furthermore, this reaction may malfunction due to a downgraded HPA axis and other hormonal abnormalities as a result of the stress response, causing increased sensitivity to alcohol.
Other New Symptoms
The autonomic nervous system affects all the organs and systems in the body, and that is why so many wide-ranging symptoms are experienced. And because the amygdala and insula are at a heightened state of awareness of all the messages coming from the body, new fears can be “learned.” This means that even when innocuous signals come into the sensory neurons, these signals can be misinterpreted as dangerous by the amygdala and insula. This happens because some patients can tend to monitor signals from their bodies, and signals can be perpetuated. This explains why patients can develop added symptoms, which can mysteriously come and go.
Headaches and “Foggy” Head
Once again, these occur as a result of prolonged muscle tension in the head. The mind is particularly in a state of heightened arousal throughout the day, and becomes stressed and exhausted from so much stimulation. This can make the head sensitive and sore. Because there may be reduced blood pressure and blood flow to the head, this contributes to brain fog because there simply are not enough resources being channelled to the brain.
Inability to Concentrate
The mind is on edge due to the excited state of the amygdala. Furthermore, the conscious mind is “arrested” by the amygdala, as it gets bombarded with signals about the body. Therefore, the mind finds it difficult to focus on other tasks, because it is also trying to process the signals about the body.
When patients are in the state of heightened arousal about symptoms, their memory systems are reshuffled so that knowledge and memories most relevant to the symptoms will be recalled, taking precedence over other less relevant strands of thought. This makes concentrating on anything else very difficult.
Problems with Memory
An area of the brain called the hippocampus has a dual role; firstly in providing short term memory retrieval, and secondly as a “control knob” which tries to moderate the release of the stress hormones. The hippocampus becomes damaged during a chronic stress response, and no longer is able to fulfil these dual roles well. Therefore, the formation of new memories in the hippocampus is inhibited, which means that you may have problems with short term memory formation and retrieval.
Whilst this effect may seem frightening, recovery will mean that the hippocampus can return to its normal functioning.
Emotional Lability, Anxiety and Depression
The stress hormones and neurotransmitters are known to increase emotional lability and feelings of vulnerability. This causes a wide variety of added psychiatric complaints and further learned fears, especially depression and sometimes agoraphobia. Your amygdala is deliberately trying to make you feel anxious, as it is trying to warn you of danger.
Susceptibility to Stress
The long term arousal of the amygdala means that stress hormone release can become poorly controlled. Therefore, external events which have little to do with bodily symptoms make you feel far more stressed than normal. You may perceive the world as more dangerous than it actually is, and this is made worse by the fear of increased symptoms because of stress.
Many patients become prone to panic attacks, which are known to be mediated by the amygdala. Prolonged worry may mean that the amygdala becomes trigger happy, triggering at the slightest negative signal from the body.
It may detect certain bodily changes such as blood pressure increasing as a result of an external event, it prepares for a panic attack, and hence this becomes a self-fulfilling prophecy: The amygdala and the conscious mind fear a panic attack coming on, and this in itself initiates it.
In general, if you experience increased external stress, this makes the symptoms even worse. This is because the stressful events impact on an already fatigued and sensitized mind and body.
Inability to Feel Enjoyment
In some patients, changes may occur in the brain’s opioid system. This system becomes hyperactive. This gives the feeling of numbness, and other psychological symptoms including “anhedonia” (the inability to feel pleasure), and a sense of being cut off from life.
And Again, Finally.
I do believe that these symptoms are temporary – that they are due to systemic functional changes in the body, rather than permanent organic damage. Stopping the amygdala and insula’s hyper-reactions allows the body to trigger the parasympathetic system, meaning the body’s own healing mechanisms can bring it back to balance and homeostasis.