Brain cells

When I woke up, I had this image of brain cells acting like sorting sponges. There must be all sorts of default output signals if the inputs aren’t optimal, with maybe certain types of neurons getting priority.
It’s actually quite crazy when you think about it – regaining mobility when you’re shielding yourself from sound (experienced), or the loosing way round.
 
In the same way as we have certain immune cells primed or more easily activated we can have certain neural cells, specific groups of neurons, primed and therefore closer to (or further from) their threshold potential. So making them easier or harder to trigger.

The idea of either a shift in receptors or in vesicle transport (neurotransmitters are stored in vesicles at the synapse right?) is interesting as I can see both impacting things.

And quite small shifts in a couple of interconnected systems could have quite significant effects I think.
 
@Timko I don’t know about others but I don’t think it needs to be one or the other. I see a few interconnected systems at play.

You could have something like the issues with interferon-response resolution @jnmaciuch talks about but also something a little off with say certain NK cells or their receptors or populations and also what is being talked about here with another vulnerability or susceptibility at the synapse, with certain neuronal populations that are perhaps sensitive to glutamatergic dysregulation. That these may all interact and amplify or perpetuate small issues in the other wouod mean small changes can cascade or ramp up and down with little pockets hidden away in certain cells at other times. And different people may have different susceptibility so the same underlying mechanism and disease could manifest itself a little differently in different people.
 
The other thing I wanted to post about is the relation of a brain cell-based theory to psychiatry and psychology.

It interests me that a lot of advocates who are keen on ME/CFS being 'neurological' or involving 'neuroinflammation' are also most vociferous about denying it is psychological or psychiatric. Yet all psychiatric disorders involve the brain and qhite a lot of understood brain disorders have psychiatric features, even if this is often usefully separated out as 'neuropsychiatric'. I think both views are well-founded so why do they seem at odds?

The first problem I see is the idea that ME/CFS is psychological where psychological is used to mean 'just a belief' in lay terms or maybe 'psychodynamic' in clinical psychologists' terms. I think we can be sure it isn't.

But there are aspects of ME/CFS like brain fog that maybe should be considered as belonging to psychiatry or 'mental health', since thinking is mental. This is where the tendency to call similar problems, when they occur with MS or Parkinson's, 'neuropsychiatric'.

On the other hand ME/CFS seems to make relatively little inroad into thinking, even compared to MS and Parkinson's and to be if anything more like narcolepsy where thinking goes blank with falling asleep and you get episodes of paralysis but the thinking is normal.

One thing seems to me clearer than any of this debate - which is that the psychiatry profession, which has at times decided to change its nae to psychological medicine, has not only completely failed to deal with a condition it has claimed to be able to treat, but made things much worse. So in practical terms there is good reason not to consider ME/CFS anything to do with psychiatry.

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I think some people will ask how can ME/CFS be a brain based disease (if it is) and yet not a 'mind' disease if 'mind' is just the working of the brain? That may be worth some comments. having studied 'conscious mind' for the last two decades Ihave come to understand that around 98% of brain working probably isn't mind. It is sorting things out before showing it to mind and then sorting out how to execute what mind wants.

There are no pains in feet. There are no images in our eyes or retinae. These things occur as events somewhere deep inside the brain after a lengthy process of collation and sifting. If the mind is someone driving a car then the 'brain' and 'nervous system' include not only the Satnav, but all the things that have switches like headlights and oil pressure gauges and so on. ME/CFS might be a problem with the satnav not working properly on some new GPS software.

A particular interest of mine is that neurobiology tells us very clearly that all decisions in brains are made by individual cell, one at a time. It is physically impossible for a decision, based on a computation that responds to some signal inputs, should occur as a single event across lots of neurons. The implications of this are weird but I think they help understand just why we are so confused about mind and brain. There is no single 'me' agent in a brain. Decisions are made by individual neurons. I think that means that foot pains and sunsets must be in individual neurons too - lots of them at once. In a sense 'I' am the audience watching a Woody Allen movie about 'me' that plays around with what is real and what is seen through one or more interfaces. (The Purple Rose of Cairo in fact.)

But however, weird the structure of 'mind' really is, I see ME/CFS as being a problem at a much lower level, like the satnav or the ABS system going out of synch. And I am also very open to the idea that there is a continuing immune disturbance driving all of that.

I think Paolo is likely right though - that this is at least in part a neurological disease with a mechanism of a sort we have never thought of, let alone encountered before. That means we have to think of it but it does not necessarily mean that it will turn out to be as hard to address as some of the things we now a bit more about, like MS.
 
Trish said:
Rather than comparing ME/CFS with neurological conditions where there is recognised damage to neurons, wouldn’t a more useful comparison be migraine?
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It would make sense to look for analogies with migraine. The problem with migraine is that there still seems to be little consensus on mechanism. If we are trying to find a mechanism of a sort we have not thought of we might expect it to be similar to another mechanism we have not thought of (migraine) but if we haven't thought of either we don't seem to be further forward!!
 
Okay, very interesting.
But to understand and progress further towards understanding it, shouldn't we focus almost exclusively on the brains of severely ill patients?
Isn't the solution found in the most severely affected? Because it's clear that the disease is the same in moderate and severe cases.
For narcolepsy, for exemple, a loss of orexin in the hypothalamus was discovered through autopsies. Is it impossible to do the same for MECFS? This has been done recently, but it would need to be done on 100 brains of severely affected MECFS patients. Whether that's even feasible... I don't know. It's been done for Alzheimer's and narcolepsy... why not us?
 
Jonathan Edwards said:
But there are aspects of ME/CFS like brain fog that maybe should be considered as belonging to psychiatry or 'mental health', since thinking is mental. This is where the tendency to call similar problems, when they occur with MS or Parkinson's, 'neuropsychiatric'.
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It seems to me that the psychiatric disease closer to ME/CFS is schizophrenia. Negative symptoms of schizophrenia resemble brain fog, especially in men who developed ME/CFS at a very young age. This is my impression. And this is certainly true in my case. Negative symptoms of schizophrenia have no cure to this day and they are the major source of disability in that condition.

But I now think that this may be only a superficial resemblance. In my unsupervised clustering of human diseases based on the latest genetic data (GWAS + WGS for 28 common diseases including ME/CFS), ME/CFS is clearly outside the cluster of psychiatric diseases (CompareME).
 
I wonder if there can be things learnt from findings like the drop off in grip strength on repeated grips here?

What sort of neural cells and mechanisms could be involved there? That seems like perhaps a more known or understood area than some others?
 
We need more ME/CFS brain autopsies. How many have been competently performed in the last almost half century?

Moreover, we don't just need pathologists that have a good idea of what they are looking for, we need to ensure they don't find only and precisely what they are looking for due to bias, i.e., you can find all kinds of things in brains that might be irrelevant, but in the wrong study might be considered causal. Alzheimers is a prime example.
 
paolo said:
It seems to me that the psychiatric disease closer to ME/CFS is schizophrenia.
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Maybe, I was not suggesting a similarity to any particular condition but that some conditioons where we know some pathology can have similar symptoms that tend to be called neuropsychiatric. Schizophrenia, where no very clear pathology is known, tends to be called psychiatric.

I think it is interesting that there is genetic overlap with one or two psychiatric conditions, like schizophrenia, but I am not sure that that would be a good reason to classify ME/CFS under a particular heading. A key part of the disability in schizophrenia relates to abnormal thoughts such as delusions and hallucinations, and also paranoia, which we do not see in ME/CFS.

The gene overlaps for sleep disorders and alcohol dependence are interesting.
 
I am concerned about the practical ( e.g., insurance and treatment) and cultural implications of a neuropsychiatric heading.

Channelopathies, which certainly resemble ME/CFS, fall under a neurology umbrella. They are considered neurological, not neuropsychiatric, even though cognitive and emotional etc domains are influenced by, and can present through, the disease, not just muscle weakness, fatigue and PEM.
 
duncan said:
I am concerned about insurance and cultural implications of a neuropsychiatric heading.
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As I said, I am equally concerned about psychiatrists being involved, considering their past incompetence. I am not suggesting a heading. I am simply discussing the paradox raised by all the various bits of evidence we have at hand. Neurology seems to me as good a place as any for now but unlike channelopathies we do not have a mechanism to hang that on.
 
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