Photoshop non responsive but mouse and save works

I have been having an issue when working on files all of a sudden Photoshop becomes unresponsive. The mouse doesn't freeze, but when I click anywhere, nothing happens. I can click on the tool bar and change tools but the cursor stays as an arrow. Key commands don't work either. Fortunately I am able to close and save the image, both CMD W or a mouse click on the close window button work.  These are big 1.5GB files, but I do have 64GB of RAM and the lastest photoshop. OS is 10.15.7. Everything works fine when I re-open for a few minutes or so

Any ideas on what the issue is?

Thanks