Volumetric differences in hippocampal subfields and associations with clinical measures in ME/CFS (Thapaliya et al., 2022)

Pyrrhus

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Volumetric differences in hippocampal subfields and associations with clinical measures in ME/CFS (Thapaliya et al., 2022)
https://onlinelibrary.wiley.com/doi/full/10.1002/jnr.25048

From the team of Leighton Barnden, Kiran Thapaliya, Donald Staines, and Sonya Marshall-Gradisnik.

The authors described the finding on Facebook:
๐—ง๐—ต๐—ฒ ๐—ธ๐—ฒ๐˜† ๐—ณ๐—ถ๐—ป๐—ฑ๐—ถ๐—ป๐—ด๐˜€ ๐—ณ๐—ฟ๐—ผ๐—บ ๐˜๐—ต๐—ถ๐˜€ ๐˜€๐˜๐˜‚๐—ฑ๐˜† ๐—ฎ๐—ฟ๐—ฒ:
- Our study found left hippocampal: subiculum, pre-subiculum and fimbria volumes were ๐™จ๐™ž๐™œ๐™ฃ๐™ž๐™›๐™ž๐™˜๐™–๐™ฃ๐™ฉ๐™ก๐™ฎ ๐™ก๐™–๐™ง๐™œ๐™š๐™ง ๐™ž๐™ฃ ๐™ˆ๐™€/๐˜พ๐™๐™Ž ๐™ฅ๐™–๐™ฉ๐™ž๐™š๐™ฃ๐™ฉ๐™จ ๐™ข๐™š๐™š๐™ฉ๐™ž๐™ฃ๐™œ ๐™ค๐™ฃ๐™ก๐™ฎ ๐™„๐˜พ๐˜พ ๐™˜๐™ง๐™ž๐™ฉ๐™š๐™ง๐™ž๐™– ๐™—๐™ช๐™ฉ ๐™ฃ๐™ค๐™ฉ ๐™›๐™ค๐™ง ๐™ˆ๐™€/๐˜พ๐™๐™Ž ๐™ฅ๐™–๐™ฉ๐™ž๐™š๐™ฃ๐™ฉ๐™จ ๐™ข๐™š๐™š๐™ฉ๐™ž๐™ฃ๐™œ ๐™๐™ช๐™ ๐™ช๐™™๐™– ๐™˜๐™ง๐™ž๐™ฉ๐™š๐™ง๐™ž๐™–.

- Hippocampal subfield volumes were ๐™จ๐™ฉ๐™ง๐™ค๐™ฃ๐™œ๐™ก๐™ฎ ๐™–๐™จ๐™จ๐™ค๐™˜๐™ž๐™–๐™ฉ๐™š๐™™ with clinical measures (fatigue, sleep disturbance, physical activity, pain and information processing) in ๐™ˆ๐™€/๐˜พ๐™๐™Ž ๐™ฅ๐™–๐™ฉ๐™ž๐™š๐™ฃ๐™ฉ๐™จ ๐™ข๐™š๐™š๐™ฉ๐™ž๐™ฃ๐™œ ๐™„๐˜พ๐˜พ ๐™˜๐™ง๐™ž๐™ฉ๐™š๐™ง๐™ž๐™–, whereas ๐™ข๐™ค๐™™๐™š๐™ง๐™–๐™ฉ๐™š ๐™–๐™จ๐™จ๐™ค๐™˜๐™ž๐™–๐™ฉ๐™ž๐™ค๐™ฃ๐™จ were observed in ๐™ˆ๐™€/๐˜พ๐™๐™Ž ๐™ฅ๐™–๐™ฉ๐™ž๐™š๐™ฃ๐™ฉ๐™จ ๐™ข๐™š๐™š๐™ฉ๐™ž๐™ฃ๐™œ ๐™๐™ช๐™ ๐™ช๐™™๐™– ๐™˜๐™ง๐™ž๐™ฉ๐™š๐™ง๐™ž๐™–.

- Clinical measures related to ๐™˜๐™ค๐™œ๐™ฃ๐™ž๐™ฉ๐™ž๐™ซ๐™š ๐™›๐™ช๐™ฃ๐™˜๐™ฉ๐™ž๐™ค๐™ฃ, ๐™ฅ๐™–๐™ž๐™ฃ ๐™–๐™ฃ๐™™ ๐™ฅ๐™๐™ฎ๐™จ๐™ž๐™˜๐™–๐™ก ๐™–๐™˜๐™ฉ๐™ž๐™ซ๐™ž๐™ฉ๐™ฎ showed a ๐™จ๐™ฉ๐™ง๐™ค๐™ฃ๐™œ ๐™ง๐™š๐™ก๐™–๐™ฉ๐™ž๐™ค๐™ฃ๐™จ๐™๐™ž๐™ฅ with hippocampal subfield volumes in the ๐™ˆ๐™€/๐˜พ๐™๐™Ž ๐™ฅ๐™–๐™ฉ๐™ž๐™š๐™ฃ๐™ฉ๐™จ ๐™ข๐™š๐™š๐™ฉ๐™ž๐™ฃ๐™œ ๐™ค๐™ฃ๐™ก๐™ฎ ๐™„๐˜พ๐˜พ ๐™˜๐™ง๐™ž๐™ฉ๐™š๐™ง๐™ž๐™–.

- We showed that ๐™๐™ž๐™œ๐™๐™š๐™ง ๐™ฅ๐™–๐™ž๐™ฃ ๐™–๐™ฃ๐™™ ๐™›๐™–๐™ฉ๐™ž๐™œ๐™ช๐™š ๐™ก๐™š๐™ซ๐™š๐™ก๐™จ were associated with ๐™จ๐™ข๐™–๐™ก๐™ก๐™š๐™ง ๐™๐™ž๐™ฅ๐™ฅ๐™ค๐™˜๐™–๐™ข๐™ฅ๐™–๐™ก ๐™จ๐™ช๐™—๐™›๐™ž๐™š๐™ก๐™™ ๐™ซ๐™ค๐™ก๐™ช๐™ข๐™š๐™จ. Furthermore, ๐™ข๐™ค๐™ง๐™š ๐™จ๐™š๐™ซ๐™š๐™ง๐™š ๐™จ๐™ก๐™š๐™š๐™ฅ ๐™™๐™ž๐™จ๐™ฉ๐™ช๐™ง๐™—๐™–๐™ฃ๐™˜๐™š ๐™–๐™ฃ๐™™ ๐™ฅ๐™ค๐™ค๐™ง๐™š๐™ง ๐™ž๐™ฃ๐™›๐™ค๐™ง๐™ข๐™–๐™ฉ๐™ž๐™ค๐™ฃ ๐™ฅ๐™ง๐™ค๐™˜๐™š๐™จ๐™จ๐™ž๐™ฃ๐™œ ๐™จ๐™˜๐™ค๐™ง๐™š๐™จ were also associated with ๐™ก๐™–๐™ง๐™œ๐™š๐™ง ๐™จ๐™ช๐™—๐™›๐™ž๐™š๐™ก๐™™ ๐™ซ๐™ค๐™ก๐™ช๐™ข๐™š๐™จ ๐™ž๐™ฃ ๐™ˆ๐™€/๐˜พ๐™๐™Ž ๐™ฅ๐™–๐™ฉ๐™ž๐™š๐™ฃ๐™ฉ๐™จ ๐™ข๐™š๐™š๐™ฉ๐™ž๐™ฃ๐™œ ๐™ค๐™ฃ๐™ก๐™ฎ ๐™„๐˜พ๐˜พ ๐™˜๐™ง๐™ž๐™ฉ๐™š๐™ง๐™ž๐™–.

- Therefore, our study demonstrated that ๐™จ๐™ฉ๐™ง๐™ž๐™˜๐™ฉ ๐™˜๐™–๐™จ๐™š ๐™™๐™š๐™›๐™ž๐™ฃ๐™ž๐™ฉ๐™ž๐™ค๐™ฃ๐™จ ๐™–๐™ง๐™š ๐™š๐™จ๐™จ๐™š๐™ฃ๐™ฉ๐™ž๐™–๐™ก in the investigation of the ๐™ฅ๐™–๐™ฉ๐™๐™ค๐™ฅ๐™๐™ฎ๐™จ๐™ž๐™ค๐™ก๐™ค๐™œ๐™ฎ ๐™ค๐™› ๐™ˆ๐™€/๐˜พ๐™๐™Ž.

Abstract:
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients suffer from a cognitive and memory dysfunction. Because the hippocampus plays a key role in both cognition and memory, we tested for volumetric differences in the subfields of the hippocampus in ME/CFS.

We estimated hippocampal subfield volumes for 25 ME/CFS patients who met Fukuda criteria only (ME/CFSFukuda), 18 ME/CFS patients who met the stricter ICC criteria (ME/CFSICC), and 25 healthy controls (HC).

Group comparisons with HC detected extensive differences in subfield volumes in ME/CFSICC but not in ME/CFSFukuda. ME/CFSICC patients had significantly larger volume in the left subiculum head (pโ€‰<โ€‰0.001), left presubiculum head (p = 0.0020), and left fimbria (p = 0.004).

Correlations of hippocampus subfield volumes with clinical measures were stronger in ME/CFSICC than in ME/CFSFukuda patients. In ME/CFSFukuda patients, we detected positive correlations between fatigue and hippocampus subfield volumes and a negative correlation between sleep disturbance score and the right CA1 body volume. In ME/CFSICC patients, we detected a strong negative relationship between fatigue and left hippocampus tail volume. Strong negative relationships were also detected between pain and SF36 physical scores and two hippocampal subfield volumes (left: GC-ML-DG head and CA4 head).

Our study demonstrated that volumetric differences in hippocampal subfields have strong statistical inference for patients meeting the ME/CFSICC case definition and confirms hippocampal involvement in the cognitive and memory problems of ME/CFSICC patients.
(spacing added for readability)
 

Pyrrhus

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Ooh, I think I can feel my hippocampus shrinking as we speak.

Good data on our brain damage, but frightening too.
thats where I see much of our problem, residing. yup, right there.

and in my case, everything in there is boiling over and squeezed and swollen and why would proper brain function occur under such a scenario?
 

Pyrrhus

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Ooh, I think I can feel my hippocampus shrinking as we speak.
Good data on our brain damage, but frightening too.
Fortunately, the hippocampus is one of the very few parts of the brain that can regenerate itself with the process of neurogenesis.

This fact actually makes the data a lot harder to interpret, since a smaller hippocampal volume could mean either increased damage (i.e. from oxidative stress) OR it could mean impaired regeneration via neurogenesis (i.e. from nutrient depletion).

Conversely, a larger hippocampal volume could indicate increased neurogenesis, which may be a mechanism to compensate for damage elsewhere in the brain - or it could mean something else entirely.

Furthermore, a change of hippocampal volume does not necessarily mean that there is a disease process in the hippocampus itself - changes in hippocampal volume might possibly be an indicator of regenerative processes elsewhere in the brain.

However, given the key role of the hippocampus in short-term memory and the consolidation of long-term memories, I would not be the least bit surprised if there were indeed a disease process in the, um, - wait, what was I talking about again?
 

Pyrrhus

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Given that variability, what an we say about these study results? Do they really hold up as differentiating Fukuda from ICC?
I haven't had a chance to review the paper in depth.

But the fact that the authors found statistically significant differences in 7 regions when comparing ME-ICC patients to controls - while only finding one statistically significant difference when comparing CFS-Fukuda patients to controls - seems like more evidence that the ICC selects for either a more coherent group of patients, or perhaps for a more severe group of patients.

After correcting their statistical significance calculations to account for the multiple comparisons made, there were 3 regions still significantly different when comparing ME-ICC patients to controls, while there remained no statistically significant differences when comparing CFS-Fukuda patients to controls.
 

Consul

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A quote from the paper

The larger subiculum and presubiculum in ME/CFSICC patients suggest a neuroregulatory rather than a neurodegenerative response may be responsible in ME/CFS. Unexpected increases in myelination in the sensorimotor cortex which were inversely proportional to brainstem decreases were interpreted as evidence of a regulatory mechanism that maintains adequate brainstemโ€“cortical communication (Barnden et al., 2018; Thapaliya et al., 2020, 2021).
 

Wishful

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The important point is that they've found signs of abnormality, which calls for more research into brain aspects of ME. Hopefully that will shift funding to neurological studies rather than muscles, mitochondria, etc.

As for what it means, my quick guess is that ME causes changes in neurological function, which result in changes in these--and maybe other--regions of the brain. I wonder if there would be similar changes due to being bedridden or otherwise prevented from normal activities.
 

ljimbo423

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The important point is that they've found signs of abnormality, which calls for more research into brain aspects of ME. Hopefully that will shift funding to neurological studies rather than muscles, mitochondria, etc.

As for what it means, my quick guess is that ME causes changes in neurological function, which result in changes in these--and maybe other--regions of the brain.
I agree that we need A LOT more research into the brain. Many studies have already found many different changes in the brain of ME/CFS patients, at least 2-3 have found neuro-inflammation.

I don't think any significant progress into the cause of ME/CFS will be found until much more research into the brain is done.
 
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I agree that we need A LOT more research into the brain. Many studies have already found many different changes in the brain of ME/CFS patients, at least 2-3 have found neuro-inflammation.

I don't think any significant progress into the cause of ME/CFS will be found until much more research into the brain is done.
I agree, this disease 100% sits in the brain.
I like the idea that degeneration occurs via neuroregulatory mechanism, not primary neurodegenerative process. This explains why no consistent pattern in brain volume loss has been found.
The most important questions are:
1) How to reverse the pathological process fully so our brain will stop trying to compensate low blood flow to the brain and messed up mitochondrial/neurological processes. If brain homeostatis will be restored, brain tissue will regenerate and we will feel normal again, maybe not 100%, but we will be able to live normal life.
2) Maybe itโ€™s not possible to reverse neurological damage that keeps our fundamental homeostasis, but if researchers will find a treatment that will compensate the problem, again, our lives will be ok.
What Iโ€™m trying to say researchers should find a cause why brain is trying to compensate absence of normal homeostasis and find a way to restore it with and possible way.
 

Wishful

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No, itโ€™s highly unlikely that inactivity can lead to brain tissue degradation.
Not degradation, but some sort of shrinkage, either physically or functionally. It might be the brain's version of atrophy, occurring over a much shorter timeframe. Brain cells are, I think, more energetic and rapidly responding than muscle cells, so changes in usage should show physical/functional changes more quickly. I'm really just guessing here. Long-term memory pathways shouldn't change much, but the pathways involved in chatting, for example, might.