Intra brainstem connectivity is impaired in chronic fatigue syndrome, Barnden et al., 2019

When I’m at my worst and can’t speak or function , hardly aware, can’t focus etc I very much feel like I have a neurological hole in the back base of my head where basically it feels signals cAnt pass as they should. So imagine interconnecting train tracks disrupted by a big hole. It feels like this is the area all my neurological dysfunction is coming from.

It also makes sense that a deep fundamental part of the brain is affected in this illness. I just wonder when and what it will take for these tantilising “studies of interest” to become rock solid evidence used in text books about our illness. How many more such studies do we need to get there?

I’m not sure what they suppose causes this lowered signalling do they say ?
 
Abstract said:
Strong hippocampal connections with midbrain and medulla nuclei were detected for ME/CFS. When corresponding correlations from HC and ME/CFS were compared, ME/CFS connectivity deficits were detected within the brainstem between the [rostral] medulla and cuneiform nucleus and between the brainstem and hippocampus and intralaminar thalamus, but only during task. In CFS/ME, weaker connectivity between some RAS nuclei was associated with increased symptom severity
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Brainstem – subcortical connections between the DoRph and intralaminar nucleus of the thalamus, and between the rostral medulla and hippocampus were also impaired in ME/CFS. The former suggests that the phenomenon that affects intra-brainstem medulla-to-midbrain connectivity extends at least to the medial midbrain to affect ascending dorsal Raphe projections.
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Since the authors didn't provide any discussion of the direct significance of this, I will provide some speculation.

The dorsal Raphe projections are discussed on Wikipedia, but it is notable that they are rich in 5-HT1A autoreceptors and endogenous opioid receptors (The nucleus raphes dorsalis has also been implicated in naloxone-induced morphine withdrawal).

The relevant connectivity between the hippocampus and intralaminar thalamus is associated with visual learning/memory. The relevant connectivity between the rostral medulla and cuneiform nucleus is probably to do with feedforward/feedback control of eye movements.

The problem is, could this lowered activity simply be due to poorer concentration/attention of patients. (as such, it could be a consequence of the illness, not a cause...)
 
rainy said:
Does anyone know what usually happens with findings like these in ME research? Is it likely it will be attempted replicated, and would it be looked further into etc?
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History would tend to tell us that attempts at replication or further investigation won't be made, typically due to lack of funding. Not a positive response I appreciate but sadly an accurate one, hopefully I'll be proved wrong though.
 
Andy said:
History would tend to tell us that attempts at replication or further investigation won't be made, typically due to lack of funding. Not a positive response I appreciate but sadly an accurate one, hopefully I'll be proved wrong though.
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I’d like to think we are reaching a point where our is history is no longer a useful guide to our future. Perhaps that is just wishful thinking, but i need some hope.
 
So another paper from the Griffiths team. I hope they are going to be applying for some of the recently announced funding in Australia. At the same time, it would be nice to see M.E. research spread to other groups/universites in Australia.
 
InitialConditions said:
So another paper from the Griffiths team. I hope they are going to be applying for some of the recently announced funding in Australia. At the same time, it would be nice to see M.E. research spread to other groups/universites in Australia.
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We have ME/CFS researchers in many different universities across Australia. Some are much more well-known than others, but I know of ME/CFS research groups in every state and territory except Northern Territory. Leighton Barnden was originally working in Adelaide, but joined the NCNED team because funding dried (at least, that’s my understanding).

We’re anticipating that the Targeted Call for Research will result in 2-5 grants (that’s what NHMRC’s CEO said), which would be good. We don’t want all the funding to go to one group.
 
Well, if its true, no one should ever recover from Cfs then. There would be no cure, no treatment. bad prospects for sure.
 
Badpack said:
Well, if its true, no one should ever recover from Cfs then. There would be no cure, no treatment. bad prospects for sure.
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It's a puzzle why the big ME teams in say the USA aren't looking at this. If this is true, this is dynamite... How can this kind of study and conclusion be just filed away, or left to the side, or not pursued.
 
Badpack said:
Well, if its true, no one should ever recover from Cfs then. There would be no cure, no treatment. bad prospects for sure.
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The good thing is that it isn't true that no one recovers. Ron Davis in one of his seminar talks this year described how one of his former students got very ill with ME/CFS and had to quit university. A few years later, Davis saw this girl back on her feet. Apparently she had minimized her activity for a year or so and then just one day started to feel better and got into remission.
 
Marky said:
I love this study too!

One thing I wondered is what exactly is meant by "connectivity impairment"?
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I think connections working less good.

With the pathogen I suspect the brain problems start when the synaps transmission is affected.
 
lansbergen said:
I think connections working less good.

With the pathogen I suspect the brain problems start when the synaps transmission is affected.
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Yea i assumed its about neural connections? Just puzzled there is no clear definition of whats actually found (maybe there is and i just didn't see it)
 
JES said:
The good thing is that it isn't true that no one recovers. Ron Davis in one of his seminar talks this year described how one of his former students got very ill with ME/CFS and had to quit university. A few years later, Davis saw this girl back on her feet. Apparently she had minimized her activity for a year or so and then just one day started to feel better and got into remission.
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It's disappointing how little research there has been in remissions, and generally the relapsing-remitting cycle that some people have experienced. I'm one of those.

I had roughly, IIRC, 3 full cycles lasting about 2 years, with sudden drops followed by months of severe illness, then slow improvement and a new lower "normal". During each remission I was able to function at a level that allowed me a near normal life. Lower function, mental sharpness and endurance every time but still, during my 2nd remission I was able to do martial arts regularly and I more or less maintained my band schedule of ~2 times a week of several hours playing drums and the occasional show. Those remissions were not complete but for all practical matters the level of near normal activity I was able to sustain would have me considered "recovered", even though I was not.

For the last 3 years I have not had any improvement at all. The cycle has broken and seems to have established in a permanent state. This obviously would require longitudinal studies, which is impossible without guaranteed long-term funding, but it would obviously provide clues into the mechanism. Even during my remissions I had some symptoms and was not nearly as mentally sharp as I used to be, but far too many have experienced something like this to be irrelevant.

I don't know how common this is in general but I find it hard to see the similarities with the main types of MS and not think that there has to be some common link.
 
I agree, it's something I've been trying to find information on. After first being ill I slowly improved until the start of this year when I went from being able to work fulltime and being 80% of normal to housebound. In the last few weeks I've had the first slight improvements but realise I'm not likely to get back to where I was before.
I find not knowing what the future holds, and having to deal with relapses and remissions very hard to deal with.
I'm trying to prepare for the worst, but can't help but feel hopeful for a lasting remission.

I suppose it's difficult to study as you'd have to follow a cohort over a long period of time, and perhaps isn't as interesting as the biology of M.E. so therefore more difficult to attract funding?
 
rvallee said:
I had roughly, IIRC, 3 full cycles lasting about 2 years, with sudden drops followed by months of severe illness, then slow improvement and a new lower "normal".
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I had a rather similar experience in the first few years of my illness. At the peaks I never quite got good enough to resume normal life, but after improving for several months and starting to dream about being recovered again, the crashes were emotionally hard to take. I eventually noticed the crashes were precipitated by catching a cold. After 6 or 8 years the cycles just seemed to stop, leaving me permanently nearer the troughs than the peaks.
 
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