This sounds like an issue I've been having since Studio One 3. My issue is very random within the project window. When I update a song the audio will silence OR "bulge" at the beginning of the track. I can sometimes go back and update the song again and MAYBE it may go away. I have also found if I go back to the session and move all of the tracks to another part of the session window it will go away. In several cases when I moved the audio tracks in the session window the bulge in amplitude in the project window just moves whichever way I slid the files in the session window.
In the image below (from the project window) I have at position 1 showing the audio has dropped out, at position 2 the amplitude rises and then goes back to where it should be. Again this seems to happen only at the beginning of a song.
This has been a constant issue with the project window for me in S1 3 and S1 4 and on two different computers! The first time I opened a ticket and (I knew this was going to happen) the only suggestion was to uninstall/reinstall S1.
I've had the block size set to different sample rates and it can still happen. It's really annoying and it even happened when I exported a mixdown from the session window to my desktop to run the wav file through Ozone. So I don't think it's an issue with the project window since it happens when I do a mixdown as well.
Although maybe your issue is happening in the session window, it sounds similar to my issue when I mixdown to a two track.