A New Hypothesis on the Role of the Brain in Chronic Fatigue Syndrome (CFS)

(Editor’s Note: Ashok Gupta, M.A., MSc., is a researcher and chronic fatigue sufferer. Gupta has developed a hypothesis on the role of the brain, its relationship to severe emotional stress and the connection of this to CFS. The entire paper is too long to reproduce here. You may request a copy directly from ashok@cfsrecovery.com – Gupta also invites all readers to comment on the paper.)

Unconscious Amygdalar Fear Conditioning in a Subset of Chronic Fatigue Syndrome Patients


I suffered from CFS around 4 years ago while I was studying at Cambridge University, (UK). After conducting extensive research into the illness and making some interesting discoveries, I developed a theory about the cause of CFS, and then developed a program of recovery for myself. I am now fully recovered and have since been researching CFS in-depth for over two years.

As someone who has suffered from CFS and subsequently recovered, I feel that, like many patients, I can bring useful insights to the psychological and physiological processes at work. I certainly know the frustration that many CFS patient experience in terms of the lack of a medical explanation, and the prevalence of “psychosocial” explanations, which make patients feel that their real suffering is going unacknowledged.

Whether you are a patient or a doctor, I hope you will find the theory interesting even if you are highly sceptical. I have deliberately written this paper so that it is accessible to practitioners of all disciplines. I have also started developing a unique program of recovery which, as far as I am aware, has not been tried until now. I want to make it clear that I am not claiming that this is the complete answer for all patients as “CFS” may be made up of a heterogeneous population of patients, but I do believe that it is worthy of further investigation. The hypothesis is a combination of my own experience and subsequent recovery from CFS, work with other patients, and the latest thought and research in the areas of emotion and neuroscience.

Before you read on, I want to make it clear from the outset that I believe that CFS is a very real illness with real symptoms, but that there is a unique unconscious neurological process which patients are currently not aware of or in control of. This unconscious process has previously only been applied to psychiatric disorders, but the neurological process is also applicable to physiological processes. Patients are in no way responsible for their symptoms, and to control these unconscious processes requires a complete program of recovery, not simply different beliefs or perceptions about the illness.

I am looking for research partners and research funding for a study based on the therapies I am developing, as well as other research related to the hypothesis. I can be contacted by e-mail, and would value any comments and criticisms on the paper, as well as any suggestions for next steps.


No one should assume that they have Chronic Fatigue Syndrome. If you have not already done so, you should see your doctor and make sure that your symptoms are not due to any other cause. There are many other serious illnesses which can mimic the symptoms of CFS, and these have to be discounted.

Even then, the following text is only theoretical at this stage, and you should approach it with a healthy scepticism. No responsibility is accepted for its particular application to any individual. Again, if you are in any doubt about the following information, please consult your doctor and discuss it with her/him.


Hypothesis: Chronic Fatigue Syndrome is a neurophysiological disorder focusing on the amygdala. During a “traumatic” neurological event often involving acute psychological stress combined with a viral infection or other physical stressor, a conditioned network or “cell assembly” is created in the amygdala, analogous to conditioning episodes seen in severe phobias and anxiety states. This cell assembly is particularly resistant to extinction. The unconscious amygdala has become conditioned to be chronically sensitised to negative symptoms arising from the body, given that “fear” tends to generalise unconsciously during periods of severe emotional arousal. Negative signals from the viscera, or psychological and physical stress, become conditioned stimuli, and the conditioned response is a chronic sympathetic outpouring from the amygdala via various brain pathways including the hypothalamus. There may also be a reactivation of the immune system in some patients as a conditioned response, given that this was the response that was initiated during the learning episode. Pavlovian conditioning of the immune system has been demonstrated in rats.

This cell assembly then produces the CFS vicious circle, where an unconscious negative reaction to symptoms causes immune reactivation/dysfunction, chronic sympathetic stimulation leading to sympathetic dysfunction, severe continuous muscle tension, mental and physical exhaustion, and a host of other distressing symptoms and secondary complications individual to each patient. And these are exactly the symptoms that the amygdala and associated limbic structures are trained to monitor and respond to, perpetuating a vicious circle. A patient also becomes hyper-reactive to external psychological, physiological or chemical stressors due to the excited state of the amygdala, and the limbic brain’s “arresting” of areas of the cortex. Recovery from CFS may involve projections from the medial prefrontal cortex to the amygdala, to control the amygdala’s expressions.

CFS is not a psychological illness, and patients are “in the grip of” a predominantly unconscious process which they are not in control of or even aware of. Existing cognitive approaches will only have very modest effects


-There are currently many names and definitions for this illness. I want to emphasise that the hypothesis I outline in this paper may apply to a significant subgroup of CFS patients with unexplained fatigue and other symptoms. The sub-set relevant to the hypothesis may exhibit some or most of the following characteristics:

– Medium to high levels of stress immediately preceding the onset of the illness, with or without a viral or environmental trigger.

– General mental and physical exhaustion, not appreciably helped by rest

– Muscular fatigue, aches or pains

– Sore throat and/or lymph glands, and slight fever

– Post-exertional malaise

– Emotional lability and vulnerability

– Psychological or physical stress increases symptoms

– Difficulties in concentrating, and memory problems

– Autonomic dysfunction and/or gastrointestinal disorder

– Sleep disturbances (too little or too much)

Some patients may be assessed according to a stricter definition, and this may point to the existence of different etiologies to that described in this paper. Alternatively, these disorders may represent an extreme morbidity of the illness I describe in this paper.


The hypothesis expressed in this paper is hardly conventional, but I do believe that the solution to CFS may well involve a reappraisal of the way illnesses such as these are envisioned. Many of the core ideas expressed in this paper involve the work of neuroscientists involved in research on emotion. Much of their work is particularly pertinent to anxiety disorders, and has relevance for treatments. Although I would not class CFS as an anxiety disorder in the traditional sense, many researchers have commented on the psychological aspects involved in CFS. By researching the basis of cognitive emotional experience in CFS, a unique insight can be gained in to how these emotions relate to the devastating physical illness which these patients endure. I believe that only once the complex mind-body link has been solved in CFS, will the solutions to its long-term treatment present themselves. The literature and ideas which I regularly refer to can be obscure. For a good general introduction, see

* Joseph Ledoux (1998), The Emotional Brain (Weidenfeld & Nicolson), chapters 6-9

* R.D. Lane and L. Nadel (eds) (2000), “Cognitive Neuroscience of Emotion”, (Oxford University Press), especially the chapter by Joseph Ledoux.

1 Star2 Stars3 Stars4 Stars5 Stars (168 votes, average: 3.05 out of 5)

Leave a Reply