what about benzos.
I think it is quite clear that any model would have to avoid such scenarios, but I wouldn't see why there's not enough wiggle room for them to exist but that's probably something where serious neuroscientists have to get involved. To avoid an epilepsy-like phenomena one might invoke something that stops synchronisation or something of that sort but of course there's things that can allow for that given the complexity of possible dynamics.
But the important part of the epilepsy-like phenomena I’m referring to here is that repeated firing of the same single neuron would cause death in that neuron as it effectively doesn’t have time to recoup metabolic homeostasis. Restoring action potentials is one of the most (if not the most) ATP-demanding cellular activity in the human body, not to mention the time needed to restore ion gradients themselves. If a neuron can’t do this [edit: and keeps firing, it dies because it can’t keep up with basic processes for keeping the cell alive].
The idea is basically something like every time a person does any kind of exertion, their nervous system receives a tiny dose of something akin to caffeine, amphetamine, or cocaine. [Edit: Like stimulants in terms of the effect, not necessarily an actual chemical being added to the brain.] The more exertion, the larger the dose.
Yes, but I don't think there's a need to invoke a very localized theory nor global detactable changes, if I'd guess one would probably anyways want to do the opposite precisely because things would have otherwise been seen. Firing patterns are anyways pretty noisy and complex, if one say was to for example increase some noise a bit and introduce some decoupling to avoid continous network hyperexcitation, I don't a priori see why that should not be enough to get something that is "not normal" but also avoids the above problems. At least that's my extremely wishy-washy layman idea. My layman impression is that pretty much that all neurological network models are complex enough to allow for all sorts of complex scenarios.
I mean many studies have identified a bunch of different changes in brain activity with actual cocaine or caffeine intake using pretty standard methods. Some of those same general screening methods have been done, but whether you can get a meaningful comparison of “is something similar happening in ME/CFS?” is another question though.
Sure, mostly I was responding to JE’s explanation that a signal hasn’t been found yet because it could originate from a tiny circuit or single neuron, which I find implausible.
To some extent yes, but to some extent no. This discussion might be very vague, handwavy and a full of belief but of course an actual model would not be that (and nobody has ever even tried developing a neurological model of ME/CFS). I'm thinking of something that should be examinable if you know where to look (that's why I've emphasised the testability of the model in previous posts), not that it's a priori invisible to all our current means, but rather invisible to what has been done because it has to be. Just like how any other explanation of ME/CFS will have to involve something invisible to what has been done up till now. Both of those things and the presentation of ME/CFS will cause strong restrinction on how the theory would look like, I think that's where you'd want a neuroscientist involved, because quite clearly the handwavy discussions are insufficient. But any involvement now still seems too early, but say there'd be more concrete results pointing towards synapses from DecodeME replication studies and then some more, things could eventually get somewhere.
I think of ME's mechanism as a complex feedback loop, possibly involving multiple parts of the body (brain, gut, maybe other squishy bits), which in turn can be represented by a very complex mathematical equation. Changing even one of those many factors, by a microbial infection or other means, can change the overall mathematical function to positive feedback, locking it into that state. Changing another factor could switch it out of that state, but that affects other factors, which could switch it back into the ME state. While we may not know precisely how a virus can do this, I don't question the possibility of it happening.
That is a problem with experimentation. I might have had cumin many times over many years without noticing that it was blocking PEM. What happened was that I did a chore expecting PEM the next day, and noticed that it didn't show up. I'd eaten curry the previous evening. If I eaten that meal 4 days earlier, or a day after, I'd not have noticed its effect. Other people may have taken something that works well for them as a PEM blocker, but not under the circumstances (timing) that would reveal it. Maybe there are treatments that would work for people, but they have to be taken with the right cofactor. Frustrating!
Yes.. Songs on repeat in my brain for days / weeks is such a problem for me that I cannot listen to music.. (also music causes immediate symptom exacerbation)
I know very little about the specifics of how all these drugs work. I think ideally you'd test with a drug that reduces neuron firing relatively globally in the nervous system since we wouldn't know what specific neurons or regions might be more important.
For what it’s worth, my thoughts on the subject come from chatting with quite a few experts in the field about the possibility of studying neuroscience under them to solve the illness. And what I walked away with is essentially what I’m saying now—in order to test any of the specific ideas I had, I’d need to wait years if not decades for more advanced understanding across the whole field of neuroscience.