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A study I want someone to do

Discussion in 'ME/CFS research' started by Sarah94, Sep 6, 2019.

  1. Squeezy

    Squeezy Senior Member (Voting Rights)

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    No one's talked about neuroinflammation in ME and PEM. Is that not an avenue of research anymore? Jared Younger was doing it last I read? I'm crashed and can't search it. Anyone up to date? Thanks.
     
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  2. Sarah94

    Sarah94 Senior Member (Voting Rights)

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    Jarred Younger still looking at it, he was meant to be presenting at the Symposium but couldn't make it for some reason.
     
  3. Squeezy

    Squeezy Senior Member (Voting Rights)

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  4. Woolie

    Woolie Senior Member

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    Yes, but why stop there? Neurons are composed of molecules and molecules of atoms. and so on. The answer is really quite simple. The correct level of description for your question/explanation/hypothesis is the one that that best carries the explanatory burden. You will not find any capacity within the neuron itself that can explain masking, as the phenomenon is very general to a large number of cognitive demands and modalities, and has different temporal features depending on domain/modality.

    It must be hard to make sense of all this when you come into it from another background altogether. I am happy to explain, if you are open to listening.
    No, "neurons" don't retain a "mask", because neurons are cells and masks are complex physical phenomena that are processed by large numbers of interconnected neurons. You cannot mix levels of description in this way.
    Yes, we do play around with recall. I am one. Technically speaking, its cognitive psychology you're talking about (neuropsychology is when its applied to the disordered or damaged brain).
    Neurons again. Never mind.
    One final thing: when my first year undergrad students say "My brain forgot", I explain that brains don't forget, they fire and and modify their connections with repeated exposure. Its people that forget; forgetting is a cognitive phenomenon. They should not mix levels of description. If you want to explain cognitive impairments in PwMEs, you're gonna have to get used to the word.

    (edited for typos)
     
    Last edited: Sep 10, 2019
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  5. Daisybell

    Daisybell Senior Member (Voting Rights)

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    Re anaesthetics - my one and only experience has been of being hypersensitive. Out like a light and then taking ages to come round.....
    I wonder whether this is worth a thread to collate experiences?
     
  6. Annamaria

    Annamaria Senior Member (Voting Rights)

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    Unsurprising as pwME seem to be sensitive to medications generally. I had sedation for dental work and was out like a light on a minimal amount.
     
  7. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    Hi @Woolie.

    I don't buy it. But I realise my disagreement is not a personal one. Asim Roy and I co-edited a volume of Frontiers in Psychology recently on representation in the brain where we tried to make the case for the neuronal level being central to understanding brain and thought, hoping to redress a recent drift away from the neutron doctrine. This is actually what I give and write papers on when I am not doing ME, so not exactly outside my field! What I have no experience of is the practical experimental methods.

    I agree that whatever mediates a mask effect is a lot of changes in lots of neurons, but I did say neurons in the pleural. There isn't anything else to change except neurons. The network level has proved unhelpful because it tells us nothing unless we know what happens at the neuronal nodes where the computational events occur. Moreover, there are reasons to think that thoughts occur as much at the cell level as above.

    A purely psychological account may be useful as an observational account of normal brains but I am sceptical that without any biophysical underpinning it can reliably predict how things will go wrong in illness. To my mind biology does not have 'persons', except perhaps in the sense of an illusory narrative of self strung together by memories (stored in neurons), as John Locke suggested. I think Gilbert Ryle got his category mistake wrong. Thoughts are events in neurons. There isn't anywhere else for them to be.

    So I stick to the idea that if a visual input, whether image or mask, has some retained effect, that effect must be a change in the biophysics of neurons. We have clues to that sort of thing with neurofibrillary tangles in Alzheimer's disease. We also have information from anaesthesia and there are some interesting things going on in terms of biophysical mechanisms of anaesthetics in neurons that I think may be relevant. The work comes from Travis Craddock, who now works with Nancy Klimas and Gordon Broderick. Travis is a very bright guy.
     
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  8. Woolie

    Woolie Senior Member

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    To be fair, no-one really knows what role the neurofibrillary tangles play in AD. They may be causal, or they may be part of the brain's response to disease of other origin. To make things more complicated, NTs also appear in other diseases, and also in TBI and even in normal aging.
    I'm not asking you to stick to purely psychological accounts. I'm just urging you to take care to distinguish between psychological and biological levels of description, and not confuse the two.

    It is also important to remember that brains don't think. People think, and they need an entire body to do so, not just a brain. This is especially important to bear in mind in ME, because there's a strong chance that the cognitive effects observed in ME are indirect effects of more systemic problems, such as OI, as I suggested above.
     
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  9. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    Indeed. I said a clue!

    I don't remember bringing in psychological accounts - I was responding to you bringing them in with 'people'.

    I still don't know what that can mean in biological terms. The event domain of thinking is smaller than the brain, not larger. For sure, antecedent events in other parts of the body feed in, but then so do events in blind people's walking sticks, CCTV cameras and everything else in the world that has been rather oddly called 'extended mind'.

    The problem under consideration is sensory processing and potential log jams in clearing out effects (like PEM) of things that should have been forgotten or tidied away. Assuming this is a cognitive rather than an immunological problem then it seems to me to need an explanation in neurons.
     
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  10. Trish

    Trish Moderator Staff Member

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    I'm trying to get my head around your conversation, @Woolie and @Jonathan Edwards.

    My little brain hurts!

    Here's a lay person's view of 'thinking' for you to pull to pieces. If it has nothing to do with what you are talking about, feel free to say so.

    If someone has cognitive problems such as slow processing of information, I am imagining what might happen is that the information is received by, say, the eyes, transmitted from there to the bit of the brain that interprets this, and from there to the parts of the brain that connect the information with previous knowledge and stores it in short and later in long term memory.

    All that has to happen by transmission between neurons with neurotransmitters at their synapses, which requires energy and a suitable environment biochemically.

    So if there is something, either in the local area in the brain or affecting the blood that arrives in the brain that:
    - reduces the oxygen supply and/or fails to remove fast enough the CO2 and other waste products
    - affects the working of the mitochondria ('something in the blood')
    - messes up the production of particular neurotransmitters (genetically, epigenetically, biochemically)
    - changes in the neuron's environment such as temperature, acidity, availability of necessary chemicals, presence of toxins or infectious agents etc
    etc etc.
    Then transmission of messages at synapses may be disrupted or slowed or reduced in some way, leading to inefficient 'thinking'.

    As far as I can see, in my simplistic way, all thinking happens in the brain, but is of course influenced by sensory messages and chemicals received from elsewhere in the body via nerves, hormones and other chemicals.
     
  11. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    I think I agree Trish, but I get stick for doing so. Ordinary people think brains think but Gilbert Ryle the philosopher said that was a category mistake, only people think.

    I won't go on about it but my reasoning is given in an essay called 'Giving Descartes His Due' in a monograph by Hackett on category metaphysics that you are unlikely to find in Cleethorpes Public Library I am afraid.

    I don't think Woolie and I disagree about anything important.

    The bit that interests me is hidden between the neurotransmitter/synapse firing bit and the cell response. Somewhere in there is something a bit like a Xerox machine or a LASER printer that holds signal patterns for milliseconds to seconds and longer if some switch is thrown. I think Travis Craddock may have identified how that would work but it is still work in progress.
     
  12. Woolie

    Woolie Senior Member

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    Yes!

    We prepare for every cognitive event by delivering oxygenated blood to the tissue involved. We know this because its what fMRI measures - the increase in oxygenation levels that accompany activity in a particular brain region.

    And there's more: our autonomic nervous system is also involved in preparing us for a demanding mental task. Heart rate variability increases, that there is an increased blood flow to key regions.

    So you can imagine that if a person has cardivascular abnormalities like OI, its unlikely they'll be able to respond effectively to a difficult cognitive challenge.

    To me, this is an explanation worth pursuing, because it explains both the mental and the physical symptoms of ME as being consequences of the same, systemic problem. I just don't know what that is!

    And yes, waste products could have a role to play too.

    (actually, I'm not even sure that all thinking happens in the brain any more. Recent research suggests that emotion plays a really crucial role in cognition - and emotion probably involves the whole body. Obviously, the brain plays a key role, but thought might be the product of a much more complex interaction).
     
    Last edited: Sep 10, 2019
  13. Amw66

    Amw66 Senior Member (Voting Rights)

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    Waste product issue would tie back into sleep deprivation/ unrefreshing - if basic " housekeeping" is not happening, waste products could " klunk" up the works?
     
  14. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    It think it is very possible that signals derived from events in the rest of the body, like immune responses, could alter the ability of neurons to carry out the processes of thinking. The problem with metabolic suggestions involving oxygen or waste products is that:
    1. these ought to have been fairly easily identifiable by MR spectroscopy or blood sampling
    2. there ought to be ME cases where the situation is so bad that there is stroke or coma and there never is.

    This comes back to the point made by Mike Murphy, the mitochondrial chap, that ME symptoms do not look like severe metabolic defects of the sort seen in heart failure or mitochondrial failure.

    I have an interesting personal experience of a Stokes Adams attack following pushing a car in the snow. My pulse went down to below 20 and I felt so faint I had to lie on the floor immobile for several minutes. I was unable to move. However, having diagnosed the problem from my pulse rate in my chest I found I could think perfectly clearly, even if I was rather alarmed.

    Put another way the sensory sensitivity and brain fog of ME does not sound to me like shortage of blood supply and I think we would have found that by now if it was.
     
  15. Annamaria

    Annamaria Senior Member (Voting Rights)

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    I can't remember which one or more physicians said that every ME patient is in heart failure. Cheney?
     
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  16. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    Not the ones I know. Or the ones with small cardiac volumes in the various studies.
     
  17. Woolie

    Woolie Senior Member

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    I think a better model of how poor autonomic control might impact on cognition is to be found in patients with damage to the anterior cingulate. These patients exhibit a general slowness in responding, especially to challenging cognitive and physical tasks. They fail to exhibit the heart rate variability changes that occur in health people just prior to a demanding task:
    Critchley et al. (2003). Human cingulate cortex and autonomic control: converging neuroimaging and clinical evidence

    Clinically, they're just slow, and can look a little like they're depressed, although without the affective features.
     
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  18. Marco

    Marco Senior Member (Voting Rights)

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    Some might find these 'old school' techniques being proposed to avoid placebo effects in clinical trials for the treatment of fragile X syndrome (genetic ASD) interesting (I do!) :

    https://www.the-scientist.com/magazine-issue/recent-trials-for-fragile-x-syndrome-offer-hope-66305
     
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  19. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    Yes, those sorts of things sound interesting. Failure of habituation at a low electrophysiological level would be very interesting.
     
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  20. Subtropical Island

    Subtropical Island Senior Member (Voting Rights)

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    Might not be relevant but I have a question.
    I recently tried some games (Elevate and Luminosity). The task switching games were weird because I often found that I knew the correct answer (task switching working ok) but couldn’t remember how to work the controls (do you swipe from or to the direction you want? Is it the left button or the right button that says ‘yes’? Etc.). This is a rapid fire game (well, supposed to be) where I’ve successfully used the control repeatedly less than a second before but suddenly I can’t remember how it works.
    Is there a name for this? Or is that just normal?
     
    Last edited: Sep 20, 2019

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