FBI Agent Kate Moretti asks Dr. Daniel Pierce to determine the mental competency of a man being retried for murder. But the trial takes a shocking and unexpected turn when Pierce’s findings question whether the person standing trial is the same person he was six years ago. Meanwhile, Moretti is unpleasantly surprised to discover that the Assistant U.S. Attorney prosecuting the case is her soon-to-be-ex-husband Donnie Ryan.

Pierce and Moretti take on an extraterrestrial case when a woman reports that aliens have abducted her husband. When Pierce and Moretti arrive to investigate, however, they make a startling discovery. Meanwhile, things heat up between Pierce and his real-life girlfriend, Caroline, but his relationship could be jeopardized if he can't get his imaginary girlfriend, Natalie, out of his mind.

When a series of bizarre public murders occur, Pierce realizes that the killer is trying to send a message about inattentional blindness, but Donnie doubts this theory. But Pierce has a trick up his sleeve that can prove his point, and they must scramble to piece together the clues before the clever killer can make any more examples out of innocent victims.

Pierce and Morretti plunge into virtual reality to solve the murder of Kurt Simpson, a man who spent most of his time in a massive multiplayer online game called Caleidoscope. After creating an avatar of himself to investigate the crime, Pierce struggles more than ever to distinguish between reality and fantasy.

A new brain device to control tremors seems to have a defect that turns out to be far more serious than a technical malfunction, and Pierce partners with Donnie to investigate. Their unlikely alliance is tested when the case escalates to murder. Meanwhile, Lewicki learns a valuable lesson about dating.

When Moretti receives a deathbed confession about the hit-and-run murder of a teenager from 1992, she calls on Pierce to determine the ailing man's credibility. The case becomes complicated, however, when the alleged killer's physician, Dr. Hutchins, reveals that his patient’s tumor has mysteriously disappeared. Pierce and Moretti must dig deeper into the past to uncover the truth behind a shocking series of apparent homicides.

Pierce investigates a stabbing at a psychiatric hospital and becomes convinced that the hospital is full of dark secrets.

Donnie tries to help a war hero who suffers from a neurological disorder; Pierce is surprised by an old flame.

Moretti faces criminal charges after taking matters into her own hands on a dangerous case; Pierce and Donnie try to clear Kate's name.

Pierce fights for an autistic teen who is under interrogation for murder; Dean Haley attempts to convince a neuroscience prodigy to attend CLMU.

Lewicki's brother shows up unannounced; Kenny is named the key suspect in a homicide case; Lewicki is approached with an offer that makes him question Pierce's loyalty.

Pierce receives a tip that the CIA might be assassinating U.S. citizens; one of Pierce's close friends is murdered; Moretti tries to overcome her trust issues.

Pierce's mental stability is questioned and his job threatened when he is accused of stalking his ex-girlfriend, Caroline Newsome. As the situation escalates, Moretti works to find the real stalker with help from a visiting inspector from Canada.