Invest in ME Conference 12: First Class in Every Way
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Abnormal Resting-State Functional Connectivity in CFS: Results of Seed and Data-Driven Analyses.

Discussion in 'Latest ME/CFS Research' started by snowathlete, Oct 10, 2015.

  1. snowathlete

    snowathlete

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    Abnormal Resting-State Functional Connectivity in Patients with Chronic Fatigue Syndrome: Results of Seed and Data-Driven Analyses.

    Gay C, et al. Brain Connect. 2015.

    Authors
    Gay C1, Robinson ME2, Lai S3, O'Shea A4, Craggs J5, Price DD6, Staud R7.
    Author information
    Citation
    Brain Connect. 2015 Oct 9. [Epub ahead of print]

    Abstract
    Although altered resting-state functional connectivity is a characteristic of many chronic pain conditions it has not yet been evaluated in patients with chronic fatigue. Our objective was to investigate the association between fatigue and altered resting-state functional connectivity in myalgic-encephalomyelitis/chronic fatigue syndrome (ME/CFS). Thirty-six female subjects, 19 ME/CFS and 17 healthy controls completed a fatigue inventory before undergoing functional magnetic-resonance imaging. Two methods, 1) data driven and 2) model-based, were used to estimate and compare the intra-regional functional connectivity between both groups during the resting state (RS). The first approach using independent-component analysis was applied to investigate five RS-networks: the default mode network (DMN), salience network (SN), left and right fronto-parietal networks (LFPN, RFPN), and sensory-motor network (SMN). The second approach used a-priori selected seed regions demonstrating abnormal regional cerebral blood-flow (rCBF) in ME/CFS patients at rest. In ME/CFS patients, Method-1 identified decreased intrinsic connectivity among regions within the LFPN. Furthermore, the functional connectivity of the left anterior mid-cingulate with the SMN and the connectivity of the left posterior-cingulate cortex with the SN were significantly decreased. For Method-2, five distinct clusters within the right parahippocampus and occipital lobes, demonstrating significant rCBF reductions in ME/CFS patients were used as seeds. The parahippocampal seed and three occipital-lobe seeds showed altered functional connectivity with other brain regions. The degree of abnormal connectivity correlated with the level of self-reported fatigue. Our results confirm altered RS functional connectivity in patients with ME/CFS which was significantly correlated with the severity of their chronic fatigue.
     
  2. snowathlete

    snowathlete

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    Looks interesting. The finding of functional changes is not uncommon in other diseases but perhaps they are specific enough to CFS to be useful? Interesting that they reported that the level of dysfunction correlated with self reported fatigue levels.
     
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  3. Effi

    Effi Senior Member

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    I had to look some things up to really understand, so I'll share:
    Depending on the patient's condition, connectivity can be: altered, decreased, disrupted, abnormal, etc. Other conditions with altered connectivity are: Parkinson's, chronic pain, autism.

    Potential pitfalls of Resting State fMRI:
    I found that interesting too. What I'm not sure about is if this will be interpreted the way we think...
     
  4. adreno

    adreno PR activist

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    Useless, as it doesn't get us any closer to a cause or treatment. Unlikely to be specific enough for diagnosis; as well as too expensive and impractical for clinical use.
     
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  5. Sidereal

    Sidereal Senior Member

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    Plus all of these "alterations" could just be the consequence of chronic pain and other peripheral signals feeding back to the brain constantly for years.
     
  6. adreno

    adreno PR activist

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    Yes, it's only showing associations. Everything that goes on in the body is reflected (measurable) in the command center (brain).
     
  7. jimells

    jimells Senior Member

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    I don't have a "chronic pain condition" - I have a neurological / immunological illness that has pain as one of many, many symptoms.
     
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  8. Chris

    Chris Senior Member

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    Lew Lim has aimed the transcranial capsules of his new Neuro (see vielight.com and mediclights.com ) primarily at the Default Mode Network with a side glance at the Salience Network;. He has an overview of its design on his site--Google "Inventor's notes on whole brain photomodulation with the Vielight Neuro--a transcranial-intranasal light therapy combination." It will be interesting to see if this proves to be an effective therapy for ME/CFS, though he has aimed it in the first instance at Alzheimer's Does anyone have any comment on this possibility?
     
  9. Chris

    Chris Senior Member

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    Lew Lim has aimed the transcranial capsules of his new Vielight Neuro at primarily the Default Network and secondarily at the Salience Network; he has Alzheimer's as his primary target, but has just started a trial with Autism Spectrum patients too. It will be interesting to learn whether this proves to be an effective therapy for ME/CFS. Does anyone here have any suggestions on this issue? A few of us on another thread are trying out the other Vielights and a variety of other red and near infra-red devices with mixed success--an experiment still in progress.
     
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  10. Bob

    Bob

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  11. Hutan

    Hutan Senior Member

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    Abnormal Resting-State Functional Connectivity in Patients with Chronic Fatigue
    Page 18

    Hmm, seems to me that the authors are using a 'leaping to conclusions' thinking style here, at least based on the information provided in this paper. Thankfully the idea isn't given prominence; it isn't mentioned in the abstract or conclusion.
     
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  12. alex3619

    alex3619 Senior Member

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    @Woolie , what do you think about this? I do suspect a little of jumping to conclusions too fast.
     
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  13. Chris

    Chris Senior Member

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    @Hutan--I agree--it could possibly be used as a support for theories of "catastrophizing" and "central sensitivity syndrome" to provide in turn late support for the diminishing appeal of CBT and that mode of thinking about us. But I shall still follow closely the response of classes of people to Lew Lim's Neuro--he seems to be getting results with Alzheimer's, and that is no mean feat.
     
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  14. msf

    msf Senior Member

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    Haha, that bit Hutan quoted should win the Psychobabble of the Year Award.
     
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  15. Hutan

    Hutan Senior Member

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    Ha, I've seen much worse lately (try the Edwards et al paper on hysteria).

    I should have said, the paper on the whole seemed very good. As a person who knows nothing about this imaging, they seemed to explain exactly what their experimental procedures were. It was just that single sentence that seemed inexplicably out of place in what was otherwise a careful, fact-based report.
     
    Last edited: Oct 30, 2015
  16. Sidereal

    Sidereal Senior Member

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    I think this is the sort of research we can expect from the glorious new MRC-funded project.

    @Woolie
     
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  17. Woolie

    Woolie Gone now, hope to see you all again soon somewhere

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    Oh wow, @Hutan, this is exactly the kind of bad stuff we were talking about on the mind and brain thread!

    As you say, the technical stuff seems to have been done okay. But the design and interpretation is a problem!

    Most important problems:

    * No proper control for physiological factors. A bunch of spurious physiol. factors can affect fMRI: heart rate variability, blood pressure, degree of wakefulness (okay, maybe not physiological), etc. You would at least need a third control group to eliminate these

    * Use of "reverse inference" (concluding that a certain pattern of activation equals a certain psychological style). You can't do this.

    * Bad reasoning. You can't have your cake and eat it. Decreased resting state functional connectivity is generally a good thing. For example, reduced resting state functional connectivity has been touted as one of the benefits of meditation(!) and conversely, samples with schizophrenia and autism seem to show increased resting state connectivity. Here they've tried to put a negative spin on decreased resting state connectivity, because otherwise they can't explain it.

    In this study, they focused a lot on one particular resting state network, the salience network (SN), because it may have a role in pain perception, introception and emotional evaluation (read: the "somatizing" network). I think the researchers were hoping for increased connectivity in this network as that would have shown that patients are focusing too much on bodily symptoms and emotionally evaluating them too much. But they got reduced connectivity - so they made some weird claim that we can't switch between networks - we can't guide thoughts away from introspection towards externally directed cognition (although the data suggest the exact opposite).

    * Inconsistency even with other psychobabble. For example, studies of chronic pain have shown overactivation of resting state networks.

    * Wrong design? If you want to study the cognitive effects of ME, better to use active tasks, and compare patients' brain activity during these tasks with those of controls. That would be easier to interpret. I would think if you really wanted to examine fatigue specifically, you'd be better off to use a within-subjects design (same individuals on good and bad days).

    * Confusion of cause and effect. Just because the brain behaves differently from healthy controls, doesn't mean there's a problem with the brain. If someone stabbed you in the leg with a knife, you'd show "abnormal resting state activation". But in this case, your very normal brain is responding to a very unusual external stimulus.
     
    Last edited: Oct 31, 2015
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  18. Hutan

    Hutan Senior Member

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    Wow @Woolie. Glad we have you on the case.
     
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  19. Chris

    Chris Senior Member

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    @Woolie---thanks for this commentary--makes good sense to me. I like aspects of the Vielight Neuro, but was suspicious of the focus on the DMN; the Gay paper fed into this whole mix, without clarifying it for me. But the Neuro does seem to be having some good effect in the AD ongoing study, and would love to have some results from testing on ME patients.
     

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