Is there any heavy applications running that might be causing it? I know i have a few programs i have to close and finder wont close it for me, so if i try to restart when they're open it locks sometimes and the mouse is not functional, like you say. I dont know if this is the problem but it was just an idea of what could be causing it.
I used to have a mac mini and i recall something like this happening, now i think of it. I think it's just a software problem, not a hardware..