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According to Andy Gavin, the creator of Crash Bandicoot, Dr. Neo Cortex is based on Brain from Pinky and the Brain.

"I remember it clearly. The four of us were eating at this mediocre Italian near Universal and I had this idea of an evil genius villain with a big head. Obviously brainy cartoon villains have big heads. He was all about his attitude and his minions. Video games need lots of minions. Jason had become very fond of Pinky and the Brain and we imagined a more malevolent Brain with minions like the weasels in Who Framed Roger Rabbit. A villain, all full of himself, unable to conceive of ever doing anything the simple way, but constantly (in his eyes) betrayed by the incompetence of his henchmen.

I put on my silly villain voice and intoned, "If you had three neurons between you, you couldn't make a triangle!" With this attitude, his name, Doctor Neo Cortex, popped instantly into our heads."

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