Alternatively, it becomes clear that the paper is deeply flawed and we're all wasting our time being there. In such situations, keep quiet and allow the presenter to finish as quickly as possible. In 4060, you can expect to speak no more than 1 or 2 times per presentation. Make them count. If you have one or two important points then find the right time to interrupt, but get them out.
Constructive comments are almost always appropriate.
If you have thought about it and see no way that a claim in the paper can be right, then challenge the speaker. Often the source of the difficulty will be a misunderstanding about terminology, but sometimes the paper is wrong. If you are thinking about pursuing a new direction suggested by the paper and are curious whether it's been done or whether the author has thought about the direction but has decided that it wasn't worthwhile, then ask. If you have read the paper carefully and think that you are in a good position to make critical suggestions then you have every right to interrupt several times during the talk with your points. Deep conceptual questions about the methodology or about future directions for research are best left to the last ten minutes of the seminar, if time allows.