Tighten them just enough to keep them from falling off, but loose enough that you can still rotate them. Ride around the block a couple of times moving them around until you find the position that feels
most natural to you, then tighten them down the lock screws the rest of the way. It's a subjective thing.
FWIW, I found relief in using Ergon grips, but more relief getting rid of my flat bar and moving to a bar that has some sweep.
Ergon grips +
On-One Mary bars = très comfortable.