Well, we're talking about the kind of modifications that ordinary, non-invasive, high-level methods, acting through the usual sensory channels, don't allow. For example, no amount of ordinary self-help could make someone unable to feel physical pain, or can let you multiply large numbers extremely quickly in the manner of a savant. Changing someone's sexual orientation is also, at best, extremely difficult and at worst impossible. We can't seem to get rid of confirmation bias, or cure schizophrenia, or change an autistic brain into a neurotypical brain (or vice versa). There are lots of things that one might want to do to a brain that simply don't happen as long as that brain is sitting inside a skull only receiving input through normal human senses.

What I find extremely irritating is when people talk about brain modification as if it's some sort of 1) terribly dangerous thing that 2) only happens post-uploading and 3) can only be done by direct hardware (or simulated hardware) modification. The correct answer is, "none of the above".

Lists like that have a good chance of canceling out. That is, there are a bunch of ways people disagree with you because they're talking about something else.