Background: Irreversible facial paralysis can be surgically treated by importing both a new neural and a new motor muscle supply. Various donor nerves can be used. If a nerve supply other than the facial nerve is used, the patient has to adapt to generate a smile. If branches of the fifth cranial nerve are used, the patient has to learn to clench teeth and smile. Currently, controversy exists regarding whether a patient develops a spontaneous smile if a nerve other than the facial nerve is used. The authors postulate that brain adaptation in facial palsy patients can occur because of neural plasticity. The authors aimed to determine whether functional magnetic resonance imaging could topographically differentiate activity between the facial nerve- and the trigeminal nerve-related cortical areas. Methods: A new paradigm of study using functional magnetic resonance imaging based on blood oxygen level- dependent signal activation was tested on 15 voluntary healthy subjects to find a sensitive localizer for teeth clenching and smiling. Subjects smiled to stimulate the facial nerve-related cortex, clenched their jaws to stimulate the trigeminal nerve-related cortex, and tapped their finger as a control condition. Results: Smiling and teeth clenching showed distinct and consistent areas of cortical activation. Trigeminal and facial motor cortex areas were found to be distinct areas with minimal overlapping. Conclusions: The authors successfully devised a functional magnetic resonance imaging paradigm effective for activating specific areas corresponding to teeth clenching and smiling. This will allow accurate mapping of cortical plasticity in facial reanimation patients.