Gregory House is injured in a motorcycle accident in Middletown, NY and finds himself in bed next to a patient (Mos Def)[1] suffering from locked-in syndrome after a bicycling accident. His attending doctor diagnoses brain death, and suggests transplanting his heart into another patient. House notices the patient following the doctors with his eyes, and is immediately interested in taking up his case. Communicating through blinking, the patient requests transfer to Princeton Plainsboro.

As House transfers the patient to Princeton, Wilson get curious as to why House was in Middletown. The team plans to do a brain biopsy on the new patient, but he loses his eyelid movement in the operation, and with that, his only way to communicate with the doctors. Dr. Taub suggests they should use a brain–computer interface for communication with the patient. Communicating via a computer, the team takes the patient’s history. He claims he did not visit St. Louis, contradicting his wife. Unable to explain himself, his wife concludes he has had an affair. Further investigation reveals that the patient has stayed at a friend's home, in order to maintain the facade of a successful business. Unbeknownst to his wife, he was moonlighting as a janitor, where he was exposed to cadmium, leading the team to believe that he has heavy metal poisoning.

Thirteen notices that he has a tear in his epithelial cells in the eye, and a Fluorescein Stain reveals ulcerative keratitis. As the team gets ready to perform a liver biopsy, Kutner notices a rash on Thirteen's wrist, where some of the patient's urine had spilled. He deduces that it is a rash due to Leptospirosis, which was transferred from rats, living in the basement where the patient had stayed.

At the end of the episode, Wilson finds out that House was in Middleton to see a psychiatrist, and confronts him on the issue. House reluctantly acknowledges Wilson's accusation, but says he is not going to continue any further sessions. The episode ends with Wilson predicting House will end up alone, and showing that House's vision blurs in a similar fashion to the "locked in" patient as he looks towards Wilson.