This episode's title is a reference to the 1983 comedy starring Steve Martin & Kathleen Turner, The Man With Two Brains.
When Peter and Brian are talking in the kitchen, there is a reference to Back to the Future when Peter is wearing Doc Brown's mind reading device and shouts, "It means that this damn thing doesn't work at all!"
Peter says he is The Greatest American Hero which was a superhero drama-comedy that ran from 1981-1983. Peter then sings the show's theme song "Believe It or Not", which is also the title of a previous episode called "Believe It or Not, Joe's Walking on Air".
When New Brian walks into the kitchen just before the "I Like Farts" song, Peter says, "Oh, you have a guitar!" just like the mother of the sick girl does in the film Airplane!.