Try downloading a trial version of Vuescan or Silverfast. If you don't have this problem with other software, then you know it is a problem with settings in your software (and your scanner hardware is most likely fine).
If you have the same problem using other software, than it would be your scanner itself acting up.
My local university library has an Epson 4490 that I tried using a few times. I brought in my own glass to lay the negatives flat, and used the Epson scanning software. That scanner had seen a lot of use and acted very quirky. I figured out a protocol that worked for me though (but it was a pain in the ass, and very slow). I had to turn it on, let it warm up, do a preview scan, wait for an error message after what seemed like an alignment problem, and then turn it off for about 5 seconds, turn it back on (meanwhile I have to close and re-open the software for it to see the scanner again). Luckily, in the advanced mode it kept my previous preview scan even after closing and opening the software. So I was able to immediately just hit "scan" and let it go. It worked fine until the scanner head returned after each pass. Once it did one pass, then returned, it would stop working, and need resetting.
Some other protocols to try and make it work were giving me oddly stretched or misaligned images (wasn't scanning the portion of the negative I had outlined), which is partly why I think it is a head alignment issue.
Anyways, good luck! I hope it's not a hardware problem, and hope you figure out settings that are making it act strange.