When a region loses the plot in the (often but not always economic) narrative of why it should be a part of a larger nation, it may strive for autonomy, but the larger nation still may have a compelling reason to keep it. That’s how large kingdoms like France and Great Britain were built in the first place. There may be little mutual advantage, but a Skåne, Corsica, or Galicia (both of them) may still be prevented from walking off on its own.
By the way, a convention on Vermont’s possible independence from the USA will be held in the Vermont Statehouse, Montpelier, Vermont, on September 14th. See here for details: https://vermontrepublic.org/2012-vermont-independence-party
Such ideas are always around…