Thread by @CiaraGlenville

A unifying *hypothesis* to explain the seemingly miraculous response to #TheNicotineTest and how it might prevent PEM in #LongCovid #vaccineinjured #mecfs - a root cause approach to PEM by modulation of the Default Mode Network in the brain. Very long thread incoming!🧵

DMN is activated in the ‘off setting’ - meditation, day dreaming, no chores get done, no brain trigger to adapt to environment, may relate to feeling of being unable to talk/move/ respond in a crash. DMN is deactivated during activity, action, cognitive/ exercise

When measuring DMN, there is ‘activity’ and ‘connectivity’ to other brain parts. Both of these are altered in ME.
⬆️ connectivity at rest in ME with areas of fatigue and depression tinyurl.com/2u8chf7z
⬇️ connectivity / less coordinated during a task tinyurl.com/mseh93wy

⬆️ Blood flow in DMN, more complex connectivity in ME at rest, ⬇️ during task and less coordinated dynamic functional connectivity tinyurl.com/mseh93wy
⬇️ connectivity with area for goal-directed cognition, decreased drive towards cognitive activity
tinyurl.com/y98awkk2

Worsening of symptoms during task correlates with increased connectivity with areas involving reward processing and cognitive control tinyurl.com/4aj9dmet

*NB* paper in ME post exercise - control patients have higher DMN activity at rest which gets switched off after exercise. Exercise induces inflammation, leaky gut and recovery needs action (DMN off) including immune response &clean up effort/ repair… tinyurl.com/5dtpzn5h

ME patients have lower DMN activity at rest which turns ON after exercise = NO clean up, lack of response to attack - PEM? See this linked comment also & citations for lack of response/ genes not being turned on, depressed immune response (lots of patients measuring this/ low NK)

https://twitter.com/renzpolster/status/1670511187405033472

Based on this diagram (adapted - not to scale!) what we need to do is increase resting DMN: promoted by meditation, yoga nidra, tVNS, microbiome modifications, reducing overall inflammation, the functional medicine approach to this complex condition we are all trying

Microbiome/gut-DMN: ‘found significant associations of gut microbial diversity with internetwork functional connectivity between executive control, DMN and sensorimotor systems.’ tinyurl.com/mry8xzua

Microbiome-DMN study in end stage renal disease which links into inflammation - ‘gut microbiota alteration impaired DMN connectivity by increasing systemic inflammation’ tinyurl.com/22vnbjnz

IL-6 inflammatory marker (common in LongCovid) linked to alterations in the DMN tinyurl.com/k3yvh3fz

Transauricular vagus nerve stimulation modulates DMN tinyurl.com/22vnbjnz
tVNS alters connectivity of DMN and neuroinflammation / nicotine link - nAChR modulates DMN, microglia, dampens cytokine expression (lots more to this) pubmed.ncbi.nlm.nih.gov/32050990/

Then in PEM/ post exercise in MECFS, we will need to *reduce* DMN activation - and this may be where nicotine plays a critical role.
Nicotine receptors are present in high concentrations in the DMN tinyurl.com/5b8tve35

Nicotine can reduce resting DMN activity tinyurl.com/bdfa4afk
‘It is possible that nicotine could be a mechanism to normalise DMN hyperactivity in obesity’ tinyurl.com/nhcmdtmz
And in controls nicotine reduces DMN activity during a task/ activity tinyurl.com/wmbptbb8

Lots more studies on DMN deactivation by nicotine. Also improves cognitive focus which is experienced by some users, this one mentions transdermal patch tinyurl.com/msehdsb6

*Continuous low dose* (patch) of nicotine may be key:
‘A constant tone of nAChR activation helps regulate DMN activity..suggests low nAChR tone may play causal role in DMN dysregulation seen in mild cognitive impairment and Alzheimer’s’ tinyurl.com/bd28mwwz

As per #TheNicotineTest best results are seen after withdrawal during rest week - Withdrawal activated the DMN tinyurl.com/4e45exa3
And during withdrawal the DMN has been observed to be hyper connected tinyurl.com/5n6vnt3n

If continuous low dose nicotine turns off the DMN for 7 days and then reactivates it during withdrawal week - is this like a reboot? Turning it on and off again? (If you’ve made it this far, that’s essentially my hypothesis!) *Disclaimer: just a hypothesis, not medical advice

What about PEM protection thereafter- people using the patch now and then after initial protocol to prevent PEM. Remembering this graph, if the DMN goes too high after exercise, nicotine may work to bring this down after exertion and protect from PEM???

And fin 😅😅

Hold on… the thread broke! Give me a few mins and I’ll fix it!

Think you can start from the bottom here to get rest of thread, sorry to add more confusion! The thread broke

https://twitter.com/ciaraglenville/status/1671530019632324609