Descartes, having argued for a strict distinction between an unextended thinking substance and extended matter, still needed to explain the plain fact that a decision to move one's arm is followed by the arm actually moving, and that a physical injury produces the mental experience of pain; his answer was that the two substances interact at a specific physical location, the pineal gland, a small structure near the center of the brain which he thought, mistakenly, was uniquely unpaired and therefore suited to serve as the seat of this interaction.
The proposal was almost immediately criticized, most sharply by Princess Elisabeth of Bohemia in correspondence with Descartes himself, who pressed him on how something wholly unextended, the soul, could possibly move something extended, since ordinary physical causation, as far as anyone could describe it, seemed to require contact and comparable kinds of substance on both sides. Descartes's own answers to her never fully closed the gap, and the difficulty, often called the interaction problem, has remained interactionism's central technical weakness ever since: it is one thing to assert that mind and body interact, since ordinary experience seems to confirm it constantly, and another to explain the mechanism by which two substances differing in their most basic properties could possibly make contact.