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After experiencing hallucinations, Catherine ignores Dr. Hartramph’s advice to check into a hospital and have her medication rebalanced. Catherine needs to prepare for a TED Talk she is giving in Boston, but she may never get there as her symptoms intensify. With the botched surgery from 111 fresh on his mind, Bickman has his PTSD treated by Lina so he can get back into the operating room. Local mother, Mira, is brought into the Cube where they realize her sudden bravery is actually the absence of fear, a side effect of a rare syndrome known as Kluver-Bucy.
After her public breakdown, Catherine has issues to face at home and at work. At home, she finds out that Esme’s biological father has Leukemia and is in need of a marrow transplant from a blood relative causing Joshua and Reagan to tell Esme who her real parents are. At the Cube, Mahmoud reveals Catherine’s bipolar diagnosis to Owen who must decide if Catherine can continue working there; but Bickman steps in to argue that Mahmoud should be fired for breaking doctor/patient confidentiality. Will Catherine lose Esme and her job?
Bickman’s doorman Joey has bleeding in his brain from a brain aneurysm, and a second bleed is imminent, and likely to be fatal. During surgery, Bickman causes a complication that he has never experienced- massive bleeding. He has four minutes to repair the damage or it will result in permanent brain damage. Catherine confesses to Josh and Reagan that she told Will that Esme is her daughter. Hartramph tells Catherine that she did this to distract Will in order to hide her affair with Bickman. Catherine tells Will it’s over between them.
Lucia, 16, is brought into the Cube by her parents after many other doctors and hospitals have failed to diagnose the cause of her arm twitches, slurred speech and inability to finish her sentences.. After talking to Erica, Catherine learns that she went to camp upstate and she fears that Erica may have rabies. The test comes back positive and the disease has clearly spread to her brain. It is too late but her parents demand that Catherine find a cure. Also in the Cube, a man who was in a motorcycle accident weeks ago insists that he died in the accident and that he is now walking dead, in hell. Esme busses tables at Will’s restaurants and accidentally reveals to Will that the Hotel Mirabella is where Bickman lives, not where Catherine went for a conference.
Catherine is doing a study on the effects of music on the brain. A saxophonist plays beautiful, haunting music on a New York Street corner, but is taken to the Cube when he begins to lose his ability to play. Catherine discovers that he has a benign essential tremor, and the tremor worsens with movements of intention. Also in the hospital is a man who has been struck by lightning and is now being treated for memory deficits and everyday he becomes progressively more interested in playing and listening to the violin. It is an actual alteration in his brain caused by the lightning strike. Catherine finds she is concerned about Bickman after he was shot and may have real feelings about him.
Danny, a 20 year old male, kills his mother and arrives at the Cube saying his head hurts and he has feelings that he can’t control. He feels great hostility with apparent provocation. During this time, Catherine and everyone else have no idea of the crime he has just committed. When a brain scan reveals a pecan sized tumor pressing against regions thought responsible for the regulation of strong emotions, Bickman confers that they need to operate ASAP but will need to call his mother, leading them to discover just how dangerous Danny’s condition is. Catherine also takes on a patient who has Alien Hand syndrome, where patients lose conscious control of a limb and the “alien” hand often thwarts what the other hand is doing. Catherine reveals to Hartramph that she slept with Bickman again and lied to Will about it. Esme overhears Will and Delilah arguing at the restaurant and pieces together that they have slept together.
After suffering a minor stroke, Frankie a make-up artist comes to Catherine to help him solve the one thing that no other doctor has been able to explain- he cannot see color. Once she discovers what she thinks is the cause, she must perform an intricate and complicated surgery that she hopes will solve the problem in the end and prevent any further strokes. Bickman must save a Pulitzer- Prize winning journalist who has been shot in the head by an errant bullet during a civil uprising in Tunisia. Catherine stresses about meeting Will’s family for the first time and confronts her fears of living a regular “normal” life.
Catherine learns that her father, a jazz pianist, is in town for a rare concert appearance. Their relationship is very strained and complicated. Owen works with Dr. Reggie Stark, the Under Secretary for Health from Veterans Affairs, on a special case involving Capt. Joseph Moran who is a decorated hero suffering from a war wound that that has become unbearable. They have tried everything to alleviate the pain but nothing works. Owen decides that Catherine should handle this case. Catherine learns that he is feeling pain in his left arm, but he has no left arm- it was amputated. Ali visits Leo who is recovering after the surgery to remove his benign but life- threatening brain tumor.
Bickman is visited by two of his friends, a married couple Tracy and Jacob Martin. Tracy tells him that Jacob has gone mad. He quit his job, refuses to go back to work, has liquidated their assets, and tried to give away their penthouse to the maid. Bickman refers them to Catherine and explains to her that the Martins are major philanthropists to many health charities including the Cube, so they should receive the VIP treatment. After talking to Jacob, who claims God has touched him, she believes that he may have a centuries old condition called Jerusalem Syndrome. Reynaud returns to the Cube for chemotherapy after he had surgery to remove his malignant glioblastoma. Unfortunately, his post surgery test results are not good. Esme asks for Elizabeths’ help to impress a boy she likes at school.
On her first official day engaged to Will, the couple awkwardly runs into Bickman, who does his best to hide his surprise. Once Will leaves, Bickman tells Catherine that she is a lone wolf like him, and will never be happily married to anyone. Ali becomes insecure with her abilities as a brain surgeon, unable to match Leo’s memory recall abilities. While Catherine discusses the differences between Ali & Leo, neurologists and surgeons with Ina, she accidentally drops her engagement ring down the drain. Even further tension erupts when Dr. Lolita Mahmoud arrives. She is the medicating psychiatrist who consults at the Cube, and her view of the brain is often diametrically opposed to Catherine’s.
Will admits to Catherine that he has cheated on her in the past. Meanwhile, Dr. Bickman is the hero of the hospital after performing emergency surgery on a famous pregnant opera singer during breakfast at a hotel with a bread knife. But the singer still fainted and became comatose from hitting her head. Catherine must find out why one of her patients keeps fainting, once during her Zumba class and another time while driving, causing a minor car accident. Regan reluctantly allows Esme to include Catherine in her school project- a video documentary about her family.
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