I've had some difficulty with the non-pro version of Multiplicity and City of Heroes. I use the left computer for the primary and the computer on the right side as secondary.
During gameplay I will run into this problem. I move the mouse to the right screen and switch computers. Then I move back to the primary and drop both mouse and keyboard control in City or Heroes. If I alt tab out of COH I can see that I still have control of both mouse and keyboard in other programs. If I move back to the secondary I have control over both on the secondary but short of unloading Multiplicity and COH on the primary and restarting both I haven't been able to find a solution.