Dr Neil Harrison: Webinar on neuroimaging (MRI, fMRI, SPECT and PET scans

Woolie

Senior Member
Messages
3,263
I am very concerned about this:

Neil Harrison talk translateon said:
Cognitions and priming
Neil Harrison talk translateon said:
This is an interesting topic, which addresses the question of how we think the functioning brains. stated in several important theories that brains are a kind of predictive machine. They predict what will happen in the world around them and compare that to what's really happening. A simple example of this is the catch of a ball. In real time we put our hand where we think it should be, and our brains get feedback from the handover where it is real. This must take place in real time. To catch the ball, we have our expectations of what is going to compare with the hand feedback that which is real.

You can apply the same idea to the relationship between inflammation and fatigue. Our brains predict a degree of inflammation in the body, and compare this with the signal arrives. If these two signals do not match, it could be felt as fatigue. These are things we are currently looking to see whether there is in those who experienced the most fatigue or chronic fatigue, a large difference between absolute levels and levels predicted by the brains.

This is an idea that Mark Edwards has been working on in psychogenic movement disorder. It a new neurosciency way of reframing the fundamentally psychological problem that he believes underpins psychogenic movement disorders.

I have yet had a chance to read the other material in detail, so I may be speaking out of turn, but I urge extreme skepticism regarding anyone who claims ME or CFS or both are due to "brain dysfunction". In most cases that I've seen, this turns out to be a reframing of the psychological explanation using neuroscience language.

We have seen this happen in the pain literature, where "central sensitisation" is the new neuroscience reframing of unexplained pain. Now its not your thoughts/feelings creating the experience of pain, its your "brain", but the idea is still the same - not "real" pain, just a "misinterpretation", and treatment is with psychoactive drugs and psychotherapy. Some patients feel reassured by the new language, sounds like doctors are not saying its "all in their heads" - but fundamentally, they are saying just this but in a much more palatable way. There's a lot of hoodwinking going on there, and in the FND literature. Let's be way of the same in our illness.
 

Sasha

Fine, thank you
Messages
17,863
Location
UK
This is an idea that Mark Edwards has been working on in psychogenic movement disorder. It a new neurosciency way of reframing the fundamentally psychological problem that he believes underpins psychogenic movement disorders.

I have yet had a chance to read the other material in detail, so I may be speaking out of turn, but I urge extreme skepticism regarding anyone who claims ME or CFS or both are due to "brain dysfunction". In most cases that I've seen, this turns out to be a reframing of the psychological explanation using neuroscience language.

We have seen this happen in the pain literature, where "central sensitisation" is the new neuroscience reframing of unexplained pain. Now its not your thoughts/feelings creating the experience of pain, its your "brain", but the idea is still the same - not "real" pain, just a "misinterpretation", and treatment is with psychoactive drugs and psychotherapy. Some patients feel reassured by the new language, sounds like doctors are not saying its "all in their heads" - but fundamentally, they are saying just this but in a much more palatable way. There's a lot of hoodwinking going on there, and in the FND literature. Let's be way of the same in our illness.

I'd be interested to know what you think of Neil Harrison's interview, once you've seen it (I'm not sure that the transcript reflects yet what he actually said - @Scarecrow is still working on checking it, I think).

I'm wondering if I was confusing Neil Harrison with Mark Edwards as the person whose approach people had concerns with?

I'd be worried if only brain people were looking at our disease but it's just one part of the elephant - and the presence of brain inflammation would mean that a psychological approach would just be stupid. It would be clear that the inflammation would need addressing, surely?
 

duncan

Senior Member
Messages
2,240
How much inflammation? To what degree? How overt?

Maybe some will imply our minds are misinterpreting minor inflammation as something more significant.
 

Sasha

Fine, thank you
Messages
17,863
Location
UK
How much inflammation? To what degree? How overt?

Jarred Younger has found (with small numbers investigated so far) that PWME's brains are half a degree hotter than healthy controls, which he describes as "fever" temperatures, IIRC - even though their bodies are a normal temperature.

Maybe some will imply our minds are misinterpreting minor inflammation as something more significant.

Harrison is talking about brains, not minds.

I understand your caution about how others might make try to make unwarranted assumptions but I'm concerned about undermining what might be useful and productive research because of how others might (or might not) choose to misinterpret it.
 

Scarecrow

Revolting Peasant
Messages
1,904
Location
Scotland
I'd be interested to know what you think of Neil Harrison's interview, once you've seen it (I'm not sure that the transcript reflects yet what he actually said - @Scarecrow is still working on checking it, I think).
There's an accurate English transcription of that section in #37.
 

duncan

Senior Member
Messages
2,240
Jarred Younger has found (with small numbers investigated so far) that PWME's brains are half a degree hotter than healthy controls, which he describes as "fever" temperatures, IIRC - even though their bodies are a normal temperature.

I absolutely agree there is chronic brain inflammation at play. You are preaching to the choir.

Harrison is talking about brains, not minds.

I understand your caution about how others might make try to make unwarranted assumptions but I'm concerned about undermining what might be useful and productive research because of how others might (or might not) choose to misinterpret it.

I appreciate the distinction between brain and mind. I suspect mind will play a role for most with a psych background. I suggest you re-read what Harrison wrote and then gauge how confident you feel he is not already seeding this idea of our misinterpreting the import of our brains' inflammation. He is not saying we are willingly or consciously getting it wrong, but, on some level, it seems to me he is at least hinting that we ARE getting it wrong.
 
Last edited:

Woolie

Senior Member
Messages
3,263
Those optical illusions are the result of beneficial adaptive strategies. Chronic illnesses are not beneficial. Let's keep that difference in mind.

The idea that the brain adapts in beneficial ways is self-evident and agreed to be true. However, the idea that the brain can just malfunction independently is a hypothesis. It is a widely accepted hypothesis, no doubt, because we are biased to believe it's true since we can observe the brain, but it's still not a fact.

The brain is one of the most dynamic and complex systems in the Universe. It should not be the first option considered when hypothesizing about illnesses and should definitely not be the only option considered. There is money being dumped into Alzheimer's research centered on this brain malfunction hypothesis and anyone who is being honest and unbiased will tell you that they are not close to solving it.

So far we still have never cured any illness based on focusing on the brain as the source of the problem. I'm not attempting to make an argument here, but just want to provide a bit of a reality check if possible.
I agree with everything you say here, @cmt12.

If the cause of our ongoing illness is a malfucnction in the brain (a crazy idea if you ask me, but let's just say it is true), then we are f*****d. There will not be any way to fix that for decades, maybe centuries. Except of course for the old favourite: pscyhopharmacoloy and psychotherapy. We're stuck in exactly the same place.

If it turns out to be something more peripheral (hey, what about the immune system, now there's an idea), then understanding that better will lead to new treatments.

The sloppy thinking here is the same as in psycho explanations:
"If we can't measure anything in the body that could explain the fatigue then it must be a problem with the brain"
 

Woolie

Senior Member
Messages
3,263
I'm wondering if I was confusing Neil Harrison with Mark Edwards as the person whose approach people had concerns with?
No, Alas I'm not. The predictive brain idea is now being co-opted to explain a range of "unexplained" illnesses, and not just by Mark Edwards.

The idea goes like this:

Neural systems don't just respond to incoming information in a passive way. They constantly make predictions about what information they're most likely to receive in a given situation, and respond to the degree of mismatch between their prediction and the reality. This process can happen at many levels, a lot of which aren't amenable to awareness (e.g., comprehending sentences).

The critical idea for us is that every organism strives (not necessarily at a conscious level) to reduce the gap between expectation and reality. Expectation-reality mismatch is undesirable and must be minimised in whatever way possible.

Now, take an "unexplained" symptom like fatigue in ME (their words, not mine). In ME, the relevant systems generate a prediction that fatigue will be experienced under a certain set of circumstances (maybe as a result of previous experience like a nasty flu-like illness). An expectation is formed. As the organism recovers, incoming information begins to violate the expectation that has been formed.

Now, the systems work to avoid this kind of mismatch. Sometimes, they achieve this not by altering the expectation, but by adjusting its interpretation of the incoming information to fit the expectation. The system makes the reality "fit" the expectation. This generates the perception of fatigue when it isn't actually there.

Of course, this doesn't happen every time anyone gets ill, even seriously ill - if it did no-one would ever get better! Anyone who'd got seriously ill would still have persistent symptoms, even after they've recovered.

To get around this huge problem for the theory, it is proposed that the kind of "reality adjustment" described above happens only where there is an exceptionally powerful expectation of fatigue. First of all, a long severe "real" fatiguing illness is necessary to create the expectation in the first place (which is why Harrison is so keen on the Dubbo studies). But still, not everyone with a long severe illness has persistent symptoms. So its often suggested that individual difference may come into play - a person prone to high anxiety and/or depression, who is introspective (focused on their internal states), whose is inclined to ruminate over their symptoms, and who holds strong beliefs about the nature of their illness may be likely to develop particularly powerful expectations.

So I agree with you that there are some differences from traditional psycho explanations of fatigue. A lot of the mechanisms are said not to be amenable to conscious awareness. But I still see this as not leading us anywhere useful in understanding and treatment. And I dislike the way they have hidden the essentially psychological nature of the theory. At least the psychological explanations say it loud and say it clear, so we know its wrong!

What do you think now, @Sasha?
 
Last edited:

Kati

Patient in training
Messages
5,497
I am very concerned about this:



This is an idea that Mark Edwards has been working on in psychogenic movement disorder. It a new neurosciency way of reframing the fundamentally psychological problem that he believes underpins psychogenic movement disorders.

I have yet had a chance to read the other material in detail, so I may be speaking out of turn, but I urge extreme skepticism regarding anyone who claims ME or CFS or both are due to "brain dysfunction". In most cases that I've seen, this turns out to be a reframing of the psychological explanation using neuroscience language.

We have seen this happen in the pain literature, where "central sensitisation" is the new neuroscience reframing of unexplained pain. Now its not your thoughts/feelings creating the experience of pain, its your "brain", but the idea is still the same - not "real" pain, just a "misinterpretation", and treatment is with psychoactive drugs and psychotherapy. Some patients feel reassured by the new language, sounds like doctors are not saying its "all in their heads" - but fundamentally, they are saying just this but in a much more palatable way. There's a lot of hoodwinking going on there, and in the FND literature. Let's be way of the same in our illness.

It is exactly what is happening in Vancouver.
 

Woolie

Senior Member
Messages
3,263
I've had a good thorough read now.

It is quite hard to navigate what Harrison is saying, because, to his credit, he often offers a number of possibilities, and says things are not certain yet. But he does seem to have a favoured theory.

Harrison’s use of post-interferon patients as a model of ME suggests he thinks the “fatigue and cognitive impairments” in ME are most likely not the result of ongoing inflammation (not due to overproduction of cytokines, etc.). Rather, they reflect some change in the brain that makes us think there is inflammation when there's not. Here is the relevant bit:
google translation of transcript 79 said:
What is Interferon? Interferon is a cytokine, a protein that the body naturally produces itself as we get an infection, especially a viral infection. There are a number of different types of interferon, but is particularly interesting Interferon alpha. This is also used therapeutically to treat patients with chronic hepatitis C

… and just at this point is an interesting peculiarity that these patients chronically treated with interferon, even if they were cured of their hepatitis C, remained part of them chronically fatigued and also loved cognitive symptoms even after treatment had ended. This can be a suitable model to use for the study of the effects of activating the immune system in the long term. Why the symptoms of fatigue and cognitive impairments exist after the immune activation is stopped?

You can get a further idea of what his hypotheses are from the following passages (bolding is mine):
google translation of transcript 78 said:
You can apply the same idea to the relationship between inflammation and fatigue. Our brains predict a degree of inflammation in the body, and compare this with the signal arrives. If these two signals do not match, it could be felt as fatigue.
This is the predictive coding model I described in my earlier post.

Here are some other excerpts that hint at his theory:
google translation of transcript 79 said:
The question is whether someone with ME reacts differently to an inflammatory stimulus than someone without ME. … ME-patients [may] give a more aggressive inflammatory response to an inflammatory stimulus in the blood or the periphery. It may also be that their [inflammatory response is] exactly the same as that of people without ME… there is a difference in the way their brains processing inflammatory stimulus... It's something we are looking at.
google translation of transcript 80 said:
… people who have a natural infection such as Pfeiffer - or another virus or bacterium - in the beginning give the inflammatory response we expect. But after a few weeks or months, the signs of inflammation in the blood return to normal. What is interesting is that even the inflammation level will return to normal people who continue to suffer from chronic fatigue, cognitive impairments and a range of other complaints such as headaches. So it seems that these symptoms may persist after infection, even if the inflammation or signs of inflammation in the blood are gone.
 
Last edited:

Sasha

Fine, thank you
Messages
17,863
Location
UK
[...] Now, take an "unexplained" symptom like fatigue in ME (their words, not mine). [...]

What do you think now, @Sasha?

Now I think I'd like to see you and Neil Harrison have a discussion because he's saying that there's inflammation in the brain, so I can't see how he could consider fatigue to be without an explanation!

Harrison’s use of post-interferon patients as a model of ME suggests he thinks the “fatigue and cognitive impairments” in ME are most likely not the result of ongoing inflammation (not due to overproduction of cytokines, etc.). Rather, they reflect some change in the brain that makes us think there is inflammation when there's not.

But in the interview, he said:

Harrison said:
How can we in the future develop better diagnostic tools for ME? At present, there are a number of different possibilities. We have been working on MRI scans, and the development of new sequences that are hopefully susceptible to inflammation in the brains. This work is still at an early stage. However, we have already used a pair of sequences that are potentially susceptible to inflammation in the brains.

There is also the work from Japan, indicating that inflammation in the brains of ME patients can be determined with PET. This is very interesting and should be further developed. What has been shown in particular, is that a PET scan that is sensitive to the activation of the microglia, the brain immune cells, may be an accurate tool for the diagnosis of ME. At this time, it has only been done in nine patients, but if future studies confirm this, then this may in fact become an important diagnostic technique for ME.

So he does seem to be talking about ongoing inflammation, not inflammation that isn't there but our brains think is.

You quoted some other bits:

google translation of transcript 79 said:
The question is whether someone with ME reacts differently to an inflammatory stimulus than someone without ME. … ME-patients [may] give a more aggressive inflammatory response to an inflammatory stimulus in the blood or the periphery. It may also be that their [inflammatory response is] exactly the same as that of people without ME… there is a difference in the way their brains processing inflammatory stimulus... It's something we are looking at.

google translation of transcript 80 said:
… people who have a natural infection such as Pfeiffer - or another virus or bacterium - in the beginning give the inflammatory response we expect. But after a few weeks or months, the signs of inflammation in the blood return to normal. What is interesting is that even the inflammation level will return to normal people who continue to suffer from chronic fatigue, cognitive impairments and a range of other complaints such as headaches. So it seems that these symptoms may persist after infection, even if the inflammation or signs of inflammation in the blood are gone.

...and I'm simply confused by it. I don't understand how he expects to tell how anybody's brain processes anything; and then he's talking about signs of inflammation in the blood having disappeared but doesn't relate it to signs of ongoing inflammation in the brain (maybe I should go back and read that in context but I don't have time).

It sounds as though he's trying to come up with a sort of computational model for how the brain processes inflammatory input into the sensation of fatigue, but I don't see any of this cobblers:

Woolie said:
So its often suggested that individual difference may come into play - a person prone to high anxiety and/or depression, who is introspective (focused on their internal states), whose is inclined to ruminate over their symptoms, and who holds strong beliefs about the nature of their illness may be likely to develop particularly powerful expectations.

Which is about thoughts, not brains. My impression is that he's talking at the neural level - the level where you get optical illusions.
 

Woolie

Senior Member
Messages
3,263
Now I think I'd like to see you and Neil Harrison have a discussion because he's saying that there's inflammation in the brain, so I can't see how he could consider fatigue to be without an explanation!
@Sasha, I think he's saying that the microglial cells in the brain are responding abnormally, as if there's some infection to be dealt with or products of bodily inflammation to be managed when there isn't (the microglial cells, if I remember rightly, actually play a role in managing cytokines and other products of the inflammatory response, which can be very dangerous in the brain). So this is not really anything like inflammation as we normally understand it (you know, all those immune and other bodily responses to things like infection).

it seems to me there are two quite different ideas being discussed in this interview. The first and main one is that the symptom of fatigue in ME (and by extension, all other symptoms) are generated entirely within the brain. The second claim is that microglial cells in the brain may play a role in creating the underlying brain dysfucntion that give rise to the sensation of persistent fatigue. The two are not properly linked - no explanation is given as to how the microglial cells actually cause the changes he suggests. For the moment, I've concentrated on the first idea, which is the main thrust of Harrison's argument.
I don't understand how he expects to tell how anybody's brain processes anything; and then he's talking about signs of inflammation in the blood having disappeared but doesn't relate it to signs of ongoing inflammation in the brain (maybe I should go back and read that in context but I don't have time).
That seems to be exactly what he wants to do. Learn more about the way the brain processes information about bodily states. That's the whole point of using fMRI. Most fMRI studies aim to use evidence about brain activity during a task to make inferences about how we process information.
Which is about thoughts, not brains. My impression is that he's talking at the neural level - the level where you get optical illusions.
I'm talking here about predictive coding models of unexplained illness in general, nothing Neil Harrison said directly. But I think its a fair assumption from what he said that he's working with this model.

You are right that in the Harrison view, the mechanisms are not necessarily conscious. But there really isn't any strict distinction between a neural and a psychological explanation, they can just be different ways of describing the same phenomenon.

If you think about it, the predictive coding idea doesn't work on its own, not without referring to "unknown individual factors". We don't generally adjust reality to fit our expectations, either consciously or unconsciously. We generally do the opposite: we learn from the unexpected information and adjust our expectation. People can and do get better from illnesses, even protracted ones. So clearly most people have no problem "updating" their expectations when there is no longer any illness in the body. Why don't we? To explain this puzzle, they're forced to appeal to personality factors.

What you have then, when you think it through, is the same old, same old, in new language. No evidence of illness on medical testing = no illness, we are misperceiving reality. A new mechanism is described as to how we end up misperceiving reality, but the why is still up for grabs.
 
Last edited:

Scarecrow

Revolting Peasant
Messages
1,904
Location
Scotland
Harrison’s use of post-interferon patients as a model of ME suggests he thinks the “fatigue and cognitive impairments” in ME are most likely not the result of ongoing inflammation (not due to overproduction of cytokines, etc.). Rather, they reflect some change in the brain that makes us think there is inflammation when there's not. Here is the relevant bit:
I was wondering about that part. Harrison seems pretty clued up that post exertional malaise and fatigue are not equivalent, although clearly he's leaning towards them being connected somehow. But thinking just about fatigue, how would the interferon alpha model square with the fatigue of ME not being a steady state, the incorrect assertion that fatigue is not relieved by rest (as opposed to unrefreshing sleep)? Like many, I find that fatigue is definitely relieved by aggressive resting, and I'm not talking about recovery from PEM, to the point that sometimes I even have a little bit of pep.

Also, there are periods of near normality. For about a week last year, I had so much energy to burn that I papered my kitchen and then started stripping the wallpaper off the hall before usual service resumed and my brain suddenly decided there was a mismatch again....or not. ;)

Now I think I'd like to see you and Neil Harrison have a discussion because he's saying that there's inflammation in the brain, so I can't see how he could consider fatigue to be without an explanation!
Taking this thought a bit further, Woolie, have you considered contacting Harrison in a dual professional / patient capacity?
 

Sasha

Fine, thank you
Messages
17,863
Location
UK
Thanks for the detailed discussion, @Woolie - I have to admit I'm still not clear that he's saying what you suggest he's saying and I don't have time cross-reference and to do you justice - plus, I think this may be one of those things that's never going to get clarified without some actual debate, because you seem to be talking about what he may or may not be implying even when he doesn't say it.

I'd really like to see you in direct discussion with him!
 

Sasha

Fine, thank you
Messages
17,863
Location
UK
Taking this thought a bit further, Woolie, have you considered contacting Harrison in a dual professional / patient capacity?

+1!

I think we need to get beyond the point where we have scientists expounding and then patients being forced to speculate, in a vacuum, about what they actually meant.
 

Woolie

Senior Member
Messages
3,263
Taking this thought a bit further, Woolie, have you considered contacting Harrison in a dual professional / patient capacity?
Not really, I wouldn't normally think of doing this. People sometimes ask challenging questions at conferences. But on thew whole, most debate in research is written. Researchers explain their hypotheses and evidence in writing and other researchers respond - with either approval or criticism - in writing.

I guess when these folks write something detailed, we'll be clearer about what they really think.
 

Sasha

Fine, thank you
Messages
17,863
Location
UK
Not really, I wouldn't normally think of doing this. People sometimes ask challenging questions at conferences. But on thew whole, most debate in research is written. Researchers explain their hypotheses and evidence in writing and other researchers respond - with either approval or criticism - in writing.

I guess when these folks write something detailed, we'll be clearer about what they really think.

I was thinking of written debate, not verbal.
 

Woolie

Senior Member
Messages
3,263
The transcript of clip 77 is now here.
@Scarecrow, thanks so much for all your work posting these. The transcripts make it much easier to check if we heard correctly.

This clip focuses on the brain mechanisms that might be behind our depression, our lack of motivation and our continuing experience of sickness when there isn’t any. Again, he’s drawing on evidence from people with actual measurable inflammation in the body (not us). The implication is that once the inflammation goes, these abnormalities sometimes persist, and the result is ME/CFS.

Harrison discusses brain structures known to be involved in the subjective experience of illness and our behavioural and emotional response to it (lack of motivation, depression, general “sickness behavior”). The implication is that these temporary changes that accompany inflammation/sickness have somehow persisted in our brains after the inflammation has gone, and may still be visible in fMRI etc.

You could describe it as a neuropsychiatric model of ME. The ME is in our messed up responses, perceptions, emotions and behaviours; the model attempts to describe the different neural abnormalities that give rise to these messed up responses etc.
 
Back