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Static and dynamic functional connectivity in patients with CFS...

Discussion in 'Latest ME/CFS Research' started by Kati, Sep 30, 2016.

  1. Kati

    Kati Patient in training

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    Static and dynamic functional connectivity in patients with chronic fatigue syndrome: use of arterial spin labelling fMRI.

    https://www.ncbi.nlm.nih.gov/pubmed/27678090

    Abstract
    Studies using arterial spin labelling (ASL) have shown that individuals with chronic fatigue syndrome (CFS) have decreased regional cerebral blood flow, which may be associated with changes in functional neural networks.

    Indeed, recent studies indicate disruptions in functional connectivity (FC) at rest in chronically fatigued patients including perturbations in static FC (sFC), that is average FC at rest between several brain regions subserving neurocognitive, motor and affect-related networks.

    Whereas sFC often provides information of functional network reorganization in chronic illnesses, investigations of temporal changes in functional connectivity between multiple brain areas may shed light on the dynamic characteristics of brain network activation associated with such maladies.

    We used ASL fMRI in 19 patients with CFS and 15 healthy controls (HC) to examine both static and dynamic changes in FC among several a priori selected brain regions during a fatiguing cognitive task.

    HC showed greater increases than CFS in static FC (sFC) between insula and temporo-occipital structures and between precuneus and thalamus/striatum.

    Furthermore, inferior frontal gyrus connectivity to cerebellum, occipital and temporal structures declined in HC but increased in CFS.

    Patients also showed lower dynamic FC (dFC) between hippocampus and right superior parietal lobule. Both sFC and dFC correlated with task-related fatigue increases.

    These data provide the first evidence that perturbations in static and dynamic FC may underlie chronically fatigued patients' report of task-induced fatigue.

    Further research will determine whether such changes in sFC and dFC are also characteristic for other fatigued individuals, including patients with chronic pain, cancer and multiple sclerosis
     
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  2. RogerBlack

    RogerBlack Senior Member

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    Interesting. More subgroups would be nice.
    The ones they mention are good, but adding in CFS patients on a bad day performance would be interesting.
    (same task, same patient, just next week or whenver they're bad)
     
    ballard likes this.
  3. Woolie

    Woolie Senior Member

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    Yay! An actually really good fMRI study!

    This study aims to use fMRI as a marker for cognitive fatigue in CFS. The authors note that CFS patients complain of mental fatigue, but its not often visible in measures of task performance.

    They use a functional connectivity analysis, which looks at the correlations between activity in different brain regions. Tight correlations in activity between two regions suggest that they are working together effectively.

    The clever thing about this study is that they used a paced serial addition test that is quite prolonged and requires mental effort, so they were able to measure how brain connectivity changed as the task progressed and people began to feel more mentally fatigued (they also measured this during the task, and in fact it was true that CFS patients reported feeling more mentally fatigued as time went on).

    They found that connectivity amongst some brain regions decreased with time in the CFS patients more than in controls (suggesting they may be a marker for mental fatigue in CFS). For example, the hippocampus and the superior parietal lobule showed increased connectivity over time in controls but not in CFS patiets. This is interesting because this network of structures may play a role in effortful retrieval and attentional control, so may help to maintain alertness and arousal as healthy people progress throughout the task. However, in the CFS patients, this was not occurring.

    There is not a hint of psychobabble anywhere.
     
    Last edited: Oct 2, 2016
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  4. Justin30

    Justin30 Senior Member

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    Doesnt this just say brain damage?
     
  5. RogerBlack

    RogerBlack Senior Member

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    No. These are not lasting changes. (assuming the person recovers post post exertional malaise if any to their normal condition.)

    It measures how well the nerves connecting various areas of the brain work. When fatigued, they stop working as well.
     
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  6. RogerBlack

    RogerBlack Senior Member

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    This study requires expensive FMRI.
    Is anyone aware of any peripheral nerve conduction velocity experiments in CFS?
    This is in principle cheap and easy to do, and doesn't seem quite ridiculous that at least some of the symptoms might be caused by issues in the peripheral nerves too.
     
  7. adreno

    adreno PR activist

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    In all the years that this technology has been in use, it still hasn't been possible to develop a fMRI based diagnostic biomarker for anything. I think we are better served by metabolomics than spending money on this.
     
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  8. RogerBlack

    RogerBlack Senior Member

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    FMRI will never be (absent really cheap MRI which isn't happening this decade) a diagnostic biomarker.

    This is very, very far from saying we shouldn't spend money on it.
    Most of the existing marker studies are also useless from a patient point of view as a diagnostic test.

    If sufficiently powered, and especially if combined with studies of the same patients in other ways, it may give clues as to the progress of the disease, or subgroups.

    As an example, if you've got a population of patients with five diseases who all meet the criteria for CFS (or ME or ...), any studies on these is going to be horribly problematic.
    A test which lets you pick out a subgroup who have one underlying disease of the several in the patient population of CFS may then let you go on and study this smaller population for biomarkers or other easy tests without the larger backgound getting in the way.

    Developing a clinical test will almost always need lots of work upstream, much of which will be using tests that are ridiculously far from being a clinical test.

    From the perspective of clinical trials, FMRI may not be very expensive.
    The first source I found said $600/hr. Assuming the tasks are hour long, for 35 patients, that's only $20K.

    NIH considers 'small' grant proposals ones that do not exceed 50K in any given year.
     
    Last edited: Oct 2, 2016
  9. Woolie

    Woolie Senior Member

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    I agree. I keep banging on here about how we should be very, very wary of fMRI studies of CFS. Most are attempts to gather evidence for a psychosocial explanation. Even those that aren't - as you point out - are of limited practical value, because they are not that practical for clinical use. They also don't lead anywhere new as regards treatments.

    There needs to be a hierarchy of research priorities, which start at the bottom (immune, metabolics, etc.), and works up to the brain only when the former have been properly documented.
    Many universities have their own scanner, and staff to run it. So it may be even cheaper than that.
     
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  10. adreno

    adreno PR activist

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    Don't get me wrong - I think that the brain imaging and neuro stuff is fascinating. And I suppose the holy grail of research is identifying endophenotypes; mapping out diseases on all levels including genetic, metabolic, immune, neurophysiological, and cognitive-behavioral. But I just think that at this point in time there are more fruitful avenues of research. I also tend to believe that once the metabolic problems (as it now looks like the research is pointing towards) are sorted, the brain problems will sort themselves out as well.
     
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  11. RogerBlack

    RogerBlack Senior Member

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    I don't wholly disagree.
    However, this assumes that there will in reasonable amounts of time be 'a cure'.
    Of course I want this.
    But.
    In principle some of the work done in this lab looks like it might in principle lead to a better understanding of where the pain in many CFS patients comes from, which might lead to either treatments or a biomarker.
    'Just' finding some way to kill the pain would be enormously valuable to some.

    Translational (research which might have clinical application soon) research has to be balanced with basic research in the area.
    Without basic research in the area to form decent hypothesis on, results of 'translational' research can be hard to interpret, and target.

    Understanding the connectivity and ways that the pain and fatigue is induced in may for example get you to a subset of nerves that may be severely affected. This might then get you to (post mortem) analysis of those nerves to find out what's going on in them.
    Analysing just the affected tissue is very much more powerful than simply doing bloodwork.

    It is very certain that mitochondrial issues in the platelets (analysed in another study) are not the cause of CFS. (the mitochondrial issues identified in them may cause changes in other cells of course).
     
  12. Chris

    Chris Senior Member

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    Victoria, BC
    The Vielight Neuro, an infrared LED device using both an intranasal unit and four transcranial LED capsules aimed at the Default Mode Network of the brain, has recently been tried on Alzheimer's patients with significant success; I have been seriously thinking of buying one--does anyone posting here know about this unit, and might hazard a guess as to whether it might have some success? You can find info on Vielight's Facebook page, and on their two websites--Vielight.com and Mediclights. com. There is a long thread on this stuff under the "Alternative therapies" listing., but so far the thread has not really tackled this issue of brain connectivity head-on, so to speak.
     
  13. Woolie

    Woolie Senior Member

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    You would need to tell us about those studies, because this particular one does not address pain.

    People have been searching for decades for a way to treat chronic unrelenting pain. In the past, approaches that target central brain mechanisms have not been that successful. Morphine seems to be really effective, but then there's the drawbacks.... It seems to me the best approaches to pain always to target the source of the pain, rather than the experience of it (as generated within the brain). so I'm talking things like anti-inflammatory agents as opposed to psychoactive drugs.

    So even when you're talking about pain, I would still advocate a focus on more peripheral mechanisms.

    (as an aside, there's always a very great risk that studies examining brain responses to pain in CFS will be misused. Many here will have seen the recent surge of articles talking about "central sensitisation syndrome (CSS)", which has become the new neuro-savvy language for somatisation disorder. Its a more palatable way of saying "there's nothing wrong with you that can't be fixed with a little therapy or some psychiatric meds". Yes, that's an oversimplification of what CSS is supposed to be, but its one that happens all the time in research focusing on "unexplained" illnesses like CFS.)
     
    Last edited: Oct 4, 2016
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  14. lansbergen

    lansbergen Senior Member

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    Yes. I still wonder why levamisole decreases my MEpain and why Benzydamine cream helps too.
     
    Last edited: Oct 4, 2016
  15. adreno

    adreno PR activist

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    I believe a lot of pain simply comes from low ATP. Our muscles fatigue quickly and start to ache. Nerves are working overtime trying to stimulate flailing muscles. Or it might have something to do with calcium channels. In any case, I put my money on primarily peripheral causes.
     
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  16. RogerBlack

    RogerBlack Senior Member

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    Pain - I was using as a general stand-in for any particular CFS symptom, I should have been clearer.
     
  17. RogerBlack

    RogerBlack Senior Member

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    There has to be a significant central component.
    If I have been working particularly hard cognitively (last time it was benefit forms) and been unable to stop at will, in addition to getting PEM, global muscle ache is a symptom for me.
    This is in muscles that most certainly have not been exercised to the point they would normally cause pain at my baseline status.
     
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  18. lansbergen

    lansbergen Senior Member

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    But the central point does not have to be in the brain. I can be the innate reaction to the infectious agent that can not be removed. (Yes, I know the brain is involved in the immune response)

    Now I have improved enough I sleep like a baby. am rested in the morning and painfree but still get easily fatique and pain from using muscles. Using muscles to sit upright behind the computer for a few hours is enough to start it. If I do not rest then it gets worse and worse.

    If it was central brain mechanisme there would not be a differense between ME pain and injury pain.
     
  19. adreno

    adreno PR activist

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    You can't conclude that from your experience. I do not share your experience at all, and do not get muscle pain from mental exertion.

    Still, your experience could be explained by depletion of the ATP pool (your brain gobbles up a lot of energy) and increase in oxidative stress. Or, the stress of having to focus in a low energy scenario could lead to muscle tension.

    None of these mechanisms would involve a central component as causative (more epiphenomenal), or something that would show up on an fMRI.
     
    Valentijn likes this.
  20. Valentijn

    Valentijn Senior Member

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    Yeah, my cognitive crashes are confined to cognitive and neurological symptoms. I can't think straight, but I'm not getting muscle pain from it, etc. Conversely, my physical crashes hit me cognitively as badly as the cognitive crashes do.
     

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