I'm more inclined to believe that compression artifacts would cause fatigue due to added content, rather than any missing content. All the audible frequencies are accounted for during compression, nothing goes missing, and the idea that compression leaves "gaps" is a Pono sales line or a myth, depending on how you view the intentions of the people portraying it that way. However, unwanted things do show up in digital artifacts, and that is usually the tell. There seems to be very little evidence that anything higher than 320kbps can be reliably differentiated, and Spotify vs. Tidal proves that I think. However, it could still be argued (though extremely difficult to prove) that digital artifacts could cause fatigue over long periods. Our brains like mathematically organized relationships in sound and frequency. It's that mathematical order that's responsible for things like musical chords. Artifacting can arguably make our brain's interpretation of the mathematical order in a song more difficult, and perhaps lead to long term fatigue or stress. Proving this would be difficult though, and they'd need to find a reliable way to measure fatigue, while also removing other control variables like frequency response imbalances or low quality source material. I can tell you this: if I play the difference files I made at a reasonable volume, they are very unpleasant to listen to and would probably lead to fatigue if I did that for an extended period (like anything more than 3 minutes). The question is, once that -30db noise get overlayed with the content of an actual music signal, and I can't hear it anymore, does it still fatigue me? This issue gets at the heart of the difference between sensation and perception, or what our brains can sense and what we are conscious they can sense. That is an iceberg.