It's more that it might not adequately address what people experience in relapses.
And does this theory, like CBT and LP/neuroplasticity, predict that 'hurt does not mean harm' ie. symptoms might exacerbate, but nothing is really lost?
Simon I hope you don't mind if I jump in and offer some (probably unsatisfying) ideas, because I've been pondering the same question about relapses and damage and have some nebulous thoughts.
One thing I picked up
from articles like this is that in the brain it might be more relevant to think about
robustness of the network rather than damage. He's talking about developmental neurological disorders in the article but I think the same could apply to neurological diseases resulting from some kind of insult:
The complexity of the [circuitry of the brain] as a whole results in buffering of this noise to give a reproducible developmental outcome; in engineering terms the system is “robust”. This robustness is due not only to molecular redundancy, but also to the involvement of multiple parallel pathways at each “choice point” (“degeneracy”). Removal or alteration of many components individually may thus have little effect but will tend to sensitize the system to alterations in other components or to environmental stresses.
So for ME/CFS, there could be some underlying worsening change that is weakening some (yet to be defined) measure of robustness. Laid over that, our actual level of function and severity of symptoms could depend on other variables that may allow the brain to compensate at a given time, but the underlying problem remains (and perhaps worsens).
My hobby horse of Parkinson's could maybe get us halfway to an example (being a loss of robustness that happens to be via literal damage). A fact you see a lot is that "By the time motor symptoms appear, 50–80% of all dopaminergic neurons in the substantia nigra have degenerated." (
wiki) This seems incredible to me, but it would seem to align with
animal experiments where researchers attacked the same neurons with toxic MPTP exposure and found the mice were able to recover back to a normal apparently symptom-free phenotype (despite lacking a similar fraction of these neurons). Presumably these mice would be more susceptible to future exposures, but in the meantime they seem to be able to compensate.
I found another interesting example of the brain having an underlying state it can temporarily deviate away from
here:
Together, these findings suggest that adult cortical spine density is regulated around a stable setpoint, while spine turnover enables rewiring during learning through loss and gain of specific connections.
41,
42,
43 Intriguingly, prolonged exposure to enriched environments (EEs) can enhance spine density and dynamics,
44,
45,
46,
47 but because this enhancement does not persist beyond return to standard housing,
44 it is not clear whether enrichment can persistently modify synaptic setpoints or exactly which features drive these changes. We recently found that prey capture learning during the [critical developmental period] can reset firing rate setpoints in V1,
48 raising the possibility that homeostatic brakes on synapse density might also be persistently modifiable by active vision-dependent learning during the visual system [critical developmental period].
If ME/CFS involves a loss of synaptic density, as
that long covid abstract suggested, maybe this sort of mechanism could be part of why a ME/CFS person who's doing particularly well is sometimes able to start working and get along well enough for a bit before they relapse.
These are both examples where the loss of robustness comes from a pretty simple literal loss of neurons or synapses. But you could imagine that a network could equally lose robustness in a way that's less obvious in terms of how we're currently looking at it, but where the 'damage' could become clear after something analogous to a change in coordinate system.
pubmed.ncbi.nlm.nih.gov
link.springer.com
