Michael Stipe looks keen and eager to talk, sitting on the edge of the couch in his Knightsbridge hotel room. He’s smiling and friendly. This is going to be a good interview, I think. And then he lobs in his opening thought. "I’m really bad at Desert Island questions," he says. "I just don’t process information that way. I don’t think like that. I don’t have ‘the best REM show ’ or ‘my favourite track’ or ‘the most embarrassing thing that ever happened to me’. My thought processes don’t work that way."

Oh. Okay, then. Given that REM have a best-of in the shops — a compilation that spans the past 15 years of their 23-year life — a few "Desert Island questions" had seemed like a good idea. Apparently not. Stipe senses exactly what I’m thinking. "Well, go ahead and ask me. But you’ll get monosyllabic grunts."

In print, that might look like a sarcastic rejoinder, but that’s not how Stipe says it. He’s apologetic. And he’s sincere. When he says that he doesn’t "process information" like that, he’s absolutely right. Stipe’s brain clearly doesn’t run along the same tracks as yours or mine. Interviewing Stipe is exhausting — the usual conventions of question and answer are thrown out the window as you try to follow his thought patterns. As our conversation continues, it quickly becomes clear that those strange, obscure, tangential REM lyrics aren’t an artful construction by a songwriter trying to be mysterious: they’re an accurate reflection of how he thinks.

Stipe will, for example, pick up on a phrase he uses in one answer and effectively "riff" on it — dropping it into the next few answers in a slightly different form, almost, you begin to think, just to see how it sounds, how it fits, rather than because of what it means. During our interview, for example, the word "maths" cropped up in almost every answer; those who saw Stipe on The Frank Skinner Show will have noted how, in every anecdote, he was fixated by the height of some object off the ground ("It was yay high"), even though this had no relevance to the story. This is eerily similar to the way he will sing a phrase in a song, then try some variations on that phrase, gradually evolving the meaning with each repetition, as on the band’s big breakthrough hit, Losing My Religion: "I thought that I heard you laughing, I thought that I heard you sing, I think I thought I saw you try."

Yet, just as Stipe’s lyrics are, on paper, confusing, but somehow manage to resonate with millions of people round the world, so having a conversation with him manages to be completely draining yet strangely invigorating.

At the beginning of the period covered by the new compilation — The Best of REM: In Time 1988-2003 — REM were a big cult band, pioneers of the new alt-rock. The first album for new label Warner, 1988’s Green, changed all that, beginning a process that would see Stipe and his bandmates (the guitarist Peter Buck, bassist Mike Mills and drummer Bill Berry) become, in the early 1990s, perhaps the biggest group in the world.

All of REM raised their game on Green, but Stipe in particular re-created himself. For years, the band had been known for Stipe’s muttered and hidden vocals. But on Green, and in particular on the song World Leader Pretend, a new voice emerges. It is the voice that would soon connect with a huge audience on huge hits such as Losing My Religion and Everybody Hurts.

"World Leader Pretend was a flawed first take that I refused to re-sing, because I thought there was something perfect in its imperfection," says Stipe. "There was something emotional in that first take, and against the producer’s better wishes — and demands — I refused to sing it again. There is something delicate and raw about the vocal that breathes life into that track."

I suggest that it was a vital turning point in REM’s career, and Stipe concurs. "It followed us working with a series of producers I have great respect for, but who were pushing me in directions I wasn’t quite ready to go in. They were trying to forward me to the next grade, and I hadn’t mastered maths yet. They were wanting the vocal to be louder, questioning the lyrics, saying, ‘That doesn’t make any sense — this is a pop song, why are you writing songs that don’t make any sense?’ Well," Stipe affects a quavering, little-boy voice, "er, I dunno. Well, because I’m singing from my soul, not from my thinking brain, thank you very much. I could answer that now. But at the time, we brought producers in to make points like that, so I bought into it. So I overarticulated and overthought for several records. World Leader Pretend is the first time that I just threw it down and said: that’s the way I want it to be."

Intriguingly, the lyrics of World Leader Pretend are about taking responsibility for your actions, including any flaws: "This is my mistake. Let me make it good. I raised the wall and I will be the one to knock it down."

Stipe lists several of his other favourite vocal performances that are also on In Time — E-bow the Letter, Losing My Religion, Everybody Hurts, Man on the Moon. But there are also tracks on the best-of that Stipe didn’t even want released, among them Electrolite, a track from New Adventures in Hi-Fi that has become a live favourite. "I thought it was incomplete; I thought my contribution to it was not very strong. It just felt like another ‘list’ song. I didn’t think it was good. But Peter (Buck) argued for it, and he was right."

It works both ways, though. Stipe reveals that Buck originally hated It’s the End of the World as We Know It, REM’s dynamic set-closer. Stipe emphasises that the time right after you have recorded a song is not always a good moment to judge its worth. "In that creating head, you’re not always seeing things clearly. That’s where the dynamic of the band is so vital — our ability to rope each other back in, to pull out the best from each other, is what’s so significant about this group — and why that dynamic shifted so dramatically when Bill left us."

Explore Music

• CD Reviews

• Live Reviews

• Classical

Editor's choice

• The 100 Best Films of the Decade
• 70 facts you didn't know about Marvel
• The 50 Biggest Movies Of 2010