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

[Pyrrhus]

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 Dr. Kiran Thapaliya, Leighton Barnden, Donald Staines, and Sonya Marshall-Gradisnik.

The authors described the finding on Facebook:

𝗧𝗵𝗲 𝗸𝗲𝘆 𝗳𝗶𝗻𝗱𝗶𝗻𝗴𝘀 𝗳𝗿𝗼𝗺 𝘁𝗵𝗶𝘀 𝘀𝘁𝘂𝗱𝘆 𝗮𝗿𝗲:
- Our study found left hippocampal: subiculum, pre-subiculum and fimbria volumes were 𝙨𝙞𝙜𝙣𝙞𝙛𝙞𝙘𝙖𝙣𝙩𝙡𝙮 𝙡𝙖𝙧𝙜𝙚𝙧 𝙞𝙣 𝙈𝙀/𝘾𝙁𝙎 𝙥𝙖𝙩𝙞𝙚𝙣𝙩𝙨 𝙢𝙚𝙚𝙩𝙞𝙣𝙜 𝙤𝙣𝙡𝙮 𝙄𝘾𝘾 𝙘𝙧𝙞𝙩𝙚𝙧𝙞𝙖 𝙗𝙪𝙩 𝙣𝙤𝙩 𝙛𝙤𝙧 𝙈𝙀/𝘾𝙁𝙎 𝙥𝙖𝙩𝙞𝙚𝙣𝙩𝙨 𝙢𝙚𝙚𝙩𝙞𝙣𝙜 𝙁𝙪𝙠𝙪𝙙𝙖 𝙘𝙧𝙞𝙩𝙚𝙧𝙞𝙖.

- Hippocampal subfield volumes were 𝙨𝙩𝙧𝙤𝙣𝙜𝙡𝙮 𝙖𝙨𝙨𝙤𝙘𝙞𝙖𝙩𝙚𝙙 with clinical measures (fatigue, sleep disturbance, physical activity, pain and information processing) in 𝙈𝙀/𝘾𝙁𝙎 𝙥𝙖𝙩𝙞𝙚𝙣𝙩𝙨 𝙢𝙚𝙚𝙩𝙞𝙣𝙜 𝙄𝘾𝘾 𝙘𝙧𝙞𝙩𝙚𝙧𝙞𝙖, whereas 𝙢𝙤𝙙𝙚𝙧𝙖𝙩𝙚 𝙖𝙨𝙨𝙤𝙘𝙞𝙖𝙩𝙞𝙤𝙣𝙨 were observed in 𝙈𝙀/𝘾𝙁𝙎 𝙥𝙖𝙩𝙞𝙚𝙣𝙩𝙨 𝙢𝙚𝙚𝙩𝙞𝙣𝙜 𝙁𝙪𝙠𝙪𝙙𝙖 𝙘𝙧𝙞𝙩𝙚𝙧𝙞𝙖.

- Clinical measures related to 𝙘𝙤𝙜𝙣𝙞𝙩𝙞𝙫𝙚 𝙛𝙪𝙣𝙘𝙩𝙞𝙤𝙣, 𝙥𝙖𝙞𝙣 𝙖𝙣𝙙 𝙥𝙝𝙮𝙨𝙞𝙘𝙖𝙡 𝙖𝙘𝙩𝙞𝙫𝙞𝙩𝙮 showed a 𝙨𝙩𝙧𝙤𝙣𝙜 𝙧𝙚𝙡𝙖𝙩𝙞𝙤𝙣𝙨𝙝𝙞𝙥 with hippocampal subfield volumes in the 𝙈𝙀/𝘾𝙁𝙎 𝙥𝙖𝙩𝙞𝙚𝙣𝙩𝙨 𝙢𝙚𝙚𝙩𝙞𝙣𝙜 𝙤𝙣𝙡𝙮 𝙄𝘾𝘾 𝙘𝙧𝙞𝙩𝙚𝙧𝙞𝙖.

- We showed that 𝙝𝙞𝙜𝙝𝙚𝙧 𝙥𝙖𝙞𝙣 𝙖𝙣𝙙 𝙛𝙖𝙩𝙞𝙜𝙪𝙚 𝙡𝙚𝙫𝙚𝙡𝙨 were associated with 𝙨𝙢𝙖𝙡𝙡𝙚𝙧 𝙝𝙞𝙥𝙥𝙤𝙘𝙖𝙢𝙥𝙖𝙡 𝙨𝙪𝙗𝙛𝙞𝙚𝙡𝙙 𝙫𝙤𝙡𝙪𝙢𝙚𝙨. Furthermore, 𝙢𝙤𝙧𝙚 𝙨𝙚𝙫𝙚𝙧𝙚 𝙨𝙡𝙚𝙚𝙥 𝙙𝙞𝙨𝙩𝙪𝙧𝙗𝙖𝙣𝙘𝙚 𝙖𝙣𝙙 𝙥𝙤𝙤𝙧𝙚𝙧 𝙞𝙣𝙛𝙤𝙧𝙢𝙖𝙩𝙞𝙤𝙣 𝙥𝙧𝙤𝙘𝙚𝙨𝙨𝙞𝙣𝙜 𝙨𝙘𝙤𝙧𝙚𝙨 were also associated with 𝙡𝙖𝙧𝙜𝙚𝙧 𝙨𝙪𝙗𝙛𝙞𝙚𝙡𝙙 𝙫𝙤𝙡𝙪𝙢𝙚𝙨 𝙞𝙣 𝙈𝙀/𝘾𝙁𝙎 𝙥𝙖𝙩𝙞𝙚𝙣𝙩𝙨 𝙢𝙚𝙚𝙩𝙞𝙣𝙜 𝙤𝙣𝙡𝙮 𝙄𝘾𝘾 𝙘𝙧𝙞𝙩𝙚𝙧𝙞𝙖.

- Therefore, our study demonstrated that 𝙨𝙩𝙧𝙞𝙘𝙩 𝙘𝙖𝙨𝙚 𝙙𝙚𝙛𝙞𝙣𝙞𝙩𝙞𝙤𝙣𝙨 𝙖𝙧𝙚 𝙚𝙨𝙨𝙚𝙣𝙩𝙞𝙖𝙡 in the investigation of the 𝙥𝙖𝙩𝙝𝙤𝙥𝙝𝙮𝙨𝙞𝙤𝙡𝙤𝙜𝙮 𝙤𝙛 𝙈𝙀/𝘾𝙁𝙎.

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 (p < 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]

And here are two previous papers from the same authors:

ICC vs. Fukuda: Diffusion tensor imaging results differ based on diagnostic criteria (Thapaliya et al., 2021)
https://forums.phoenixrising.me/thr...agnostic-criteria-thapaliya-et-al-2021.85111/

A systematic review of neurological impairments in ME/CFS using neuroimaging techniques (Maksoud et al., 2020)
https://forums.phoenixrising.me/thr...syndrome-using-neuroimaging-techniques.81884/

 

[wabi-sabi]

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

Good data on our brain damage, but frightening too.

 

[Rufous McKinney]

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]

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?

 

[wabi-sabi]

This fact actually makes the data a lot harder to interpret,

I sure didn't know that about the hippocampus.

Given that variability, what an we say about these study results? Do they really hold up as differentiating Fukuda from ICC?

 

[Pyrrhus]

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]

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 brainstem–cortical communication (Barnden et al., 2018; Thapaliya et al., 2020, 2021).

 

[Wishful]

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]

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.

 

[VisualEffect]

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 it’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 I’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.

 

[VisualEffect]

I wonder if there would be similar changes due to being bedridden or otherwise prevented from normal activities.

No, it’s highly unlikely that inactivity can lead to brain tissue degradation. This is probably neuroregulatory mechanism that is trying compensate fundamental problem in the brain.

 

[ljimbo423]

I like the idea that degeneration occurs via neuroregulatory mechanism, not primary neurodegenerative process.

I like this idea too. It seems to make more sense to me.

 

[Wishful]

No, it’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.

 

[SlamDancin]

@Wishful definitely explains why some days I can use my muscles well and some days not

 

[Shanti1]

Fortunately, the hippocampus is one of the very few parts of the brain that can regenerate itself with the process of neurogenesis.

This just made my day.

 

[Rufous McKinney]

This just made my day.

yay for that!

I actually recalled a dream this morning? Guess what I was dreaming about: THIS.

I was walking around all over the place and making note of how I was fine. Doing all that.

do we call that a nightmare?

 

[pattismith]

- We showed that 𝙝𝙞𝙜𝙝𝙚𝙧 𝙥𝙖𝙞𝙣 𝙖𝙣𝙙 𝙛𝙖𝙩𝙞𝙜𝙪𝙚 𝙡𝙚𝙫𝙚𝙡𝙨 were associated with 𝙨𝙢𝙖𝙡𝙡𝙚𝙧 𝙝𝙞𝙥𝙥𝙤𝙘𝙖𝙢𝙥𝙖𝙡 𝙨𝙪𝙗𝙛𝙞𝙚𝙡𝙙 𝙫𝙤𝙡𝙪𝙢𝙚𝙨

I think I've already read that reduced volume was also found in Depression, and that low serotonin in the Hippocampus is a common feature in Depression.

I happen to find that adding Piroxicam to my regimen has been a game changer on my brain symptoms and I found a study linking Piroxicam and hippocampal serotonin.

I tried to switch to Aceclofenac, which is a more selective COX2 inhibitor than Piroxicam, but Aceclofenac had no effect whereas the Piroxicam effect is almost immediate, even with a very low dose.

Results:
Acute treatment with piroxicam promoted an antidepressant‑like effect in the FST (mouse model), which was associated with an increase in serotonin levels in the hippocampus.
This effect was potentiated in the piroxicam + sertraline group but counteracted by administration of the non-selective serotonin receptor antagonist pizotifen.
Conclusion: These results suggest that the antidepressant‑like effect of piroxicam in the FST is mediated by the serotonin system; however, by different mechanisms from those of sertraline.

https://journals.sagepub.com/doi/pdf/10.4103/0976-500X.149133
2015

 

[Judee]

Do you think it helped you with brain fog and depression too?

Also does it cause issues with stomach and intestinal bleeding since it is listed as a NSAID?

 

[pattismith]

Do you think it helped you with brain fog and depression too?

Also does it cause issues with stomach and intestinal bleeding since it is listed as a NSAID?

Piroxicam fixes my brain fog/sleepiness/drowsiness/depression.

It's dual activity on hipocampus and on cytokines probably explains this ability.

I have already taken it in the past during long periods of time, but the main problem I had was on my kidneys.

I am trying lower dose now with colchicine and I hope I will tolerate it that way because each time I stop it, I crash hard.