When mine started doing this, it was because the drive was developing bad sectors and mapping them out. The drive becomes unresponsive for some time while doing

When mine started doing this, it was because the drive was developing bad sectors and mapping them out. The drive becomes unresponsive for some time while doing that, so as each application would need a disc io it would beachball. Sadly the Apple supplied interface to S.M.A.R.T. data only gives the rosiest outer level summary so it showed "verified". Third party tools that show all the data confirmed the failing sectors, including another half dozen as I refreshed my backup.