I do believe that ME/CFS is predominantly a central nervous system issue, essentially a problem of the neurons and synapses, in how the network itself is functioning. (I do think there will be quite a bit of tissue damage, too, though.)
But at the same time, we haven’t covered all the possible roads outside the CNS. It could make sense, given the current data, to “Occam” the situation down to a network dysfunction in the CNS, but it could also be very foolish, since we may simply be missing the main puzzle piece(s) that tie(s) everything together.
Part of why the CNS/neuron/synapse angle hasn’t been explored more is practical: it’s extremely expensive, neurology as a field is biased against ME/CFS, and we lack proper models (cell, animal, organoid) to study this disease. That makes it very difficult to address the “hardware vs. software” problem in a network sense other than via beuroimaging techniques (many of which are disputed in their very usefulness). It’s frontier research, and the tools aren’t really there yet (for us).
So given all this, it actually makes a lot of sense that people investing money in ME/CFS research have not focused on the CNS. With such extreme resource constraints, it’s rational to put more emphasis on peripheral avenues that are cheaper and easier to explore. At the end of the day, it’s always a balance of cost-risk and cost-benefit – so until now, that may meant concentrating more on peripheral mechanisms, even if the real story ultimately lies in the CNS and its networks.
Saying all that, as a very severe ME/CFS patient, I personally put most of what little energy I have left for advocacy into trying to convince neurologists and neuroscientists to take this matter more seriously and actually do research on it.
Unfortunately, they still mostly dismiss the condition, but I see quite a bit of change in the under 50 year old segment of neurologists. I think this is one of the most important battles to fight next to fundraising (which is by far the most important, imo).
(If it is indeed mostly a CNS issue, much will come down to much more basic science than anyone of us could wish for, I am afraid. The Allen Institute is a body that does a lot of interesting stuff in that direction.)