I've had that too and reported it awhile ago. The AI need a bit of prodding to move along after driving about an hour or so, sometimes less. the signals will remain red and report no train approaching when there's a train sitting at the signal. In other cases, the AI will sit at stations and when told to continue, they finally start up and run. Pausing the simulator works sometimes and everything comes back to life with other weird things happening with scripted objects. After a few times of pausing, that no longer works. Quitting and resuming the saved session will work sort of, but the signals will either remain dark, although the driver hud bar shows green or other aspects. In some cases, the signals themselves show red and the AI ignores those as well as their schedule. This causes mayhem beyond what can be imagined with derailments and SPADS all over the route.
I worked N3V QA on this issue, and was told it's due to stuck threads. It appears that really complex operations with lots of drivers, schedules, and track work gets things knotted up.