interesting. your sound issue sounds game specific, and it sounds like something may be corrupting - fpse keeps your settings between loads.
I recommend reinstalling FPSE - make sure to backup your savestate and memory cards before you do (sounds like you've already done tis before). go to misc, backup. It saves them to /sdcard/fpsebackup. I recommend you copy that to another location. Then uninstall fpse. then install. Then - do not import your old settings. From the misc menu, go to memcard and save state, and point fpse to the location you copied them to. I also recommend not restore from savestates at this point, only use mem card saves for now.
Then, configure fpse how you want it. Exit fpse, make sure the settings stick. Then make a shortcut to your game from misc, shortcut. The shorcut contains all your settings, so when you use the shortcut it will use the shortcut settings, and it (hopefully) won't save anything to the main fpse settings if anything gets corrupt. After things seem to be working, then start using save states again (if you dare).
Also, I would test on a different game to see if you're having issues with a different game.