I have been experiencing the same issue with my Harmony for Xbox (essentially the same model). Spent some time with Harmony support the other day and have not had a repeat occurrence as of yet. What we did was reloaded the firmware in "safe mode".

1- remove batteries
2- plug in to computer while holding the power button
3- check for "Safe Mode" on screen.
4- reload firmware
5- reload your set-up
6- unplug remote
7- hold the "2" button while replacing batteries.

You may want to call harmony and have them walk you through this as I am just going from memory on this.