Amy, Penny, and Bernadette are excitedly discussing dresses for Howard and Bernadette's wedding. Amy reveals that her cousin and her entire wedding party had died in a carbon monoxide accident, so they could get all the unused wedding dresses for free. However, this is quickly rejected by the horrified gang. Sheldon gets fed up with the quality of conversation, unsuccessfully trying to be discreet in his blaming Penny for it, and attempts to discuss the validity of a Swiss discovery concerning faster-than-light particles at CERN, after which the three women leave for Penny's apartment.
The next day, Amy is in the Caltech cafeteria after being given a grant to purchase a strain of Mad Cow Disease, making everyone uncomfortable. However, Howard absent-mindedly complains at constantly being texted non-stop by Bernadette with pictures of the dresses they want to buy. This revelation makes Amy realize they are doing it without her, and she leaves, looking visibly upset.
Later at apartment 4A, Leonard is playing Champion Jockey: G1 Jockey & Xbox Kinect horse racing, but Sheldon becomes concerned when Amy doesn't respond to any of his attempts to contact her, and Leonard offers to drive him there to find out what's going on. When they arrive, she is playing "Everybody Hurts" on her harp, while crying, and Sheldon, unwilling to proceed, attempts to persuade Leonard to take him home. Leonard sees an opportunity and immediately knocks on Amy's door using Sheldon's triple knock, and leaves, stranding Sheldon at Amy's apartment. He says that he doesn't have to put up with this problem because he is single. Amy initially desires to be left alone, but she invites him in and explains that Penny and Bernadette's snubbing her has left her feeling depressed. After asking him to keep an open mind, she explains her desire for physical contact, and makes a list of proposals involving them getting intimate, while Sheldon makes a series of counter-proposals (French kissing) that involve less intimacy (patting her and neck massage), but will still be soothing to her. They eventually agree to just cuddle, and she snuggles up to him on her couch.
The next morning, Sheldon storms into the Caltech cafeteria completely furious, and confronts Howard and Leonard, demanding that they get their women in line. Howard and Leonard are confused. Sheldon explains that his night of building a Lego Death Star had been ruined by his having to spoon with Amy, and demands they get Penny and Bernadette in line and apologize to Amy. Leonard, confused, asks why he has to talk to Penny, since she is no longer his girlfriend. However, Sheldon does not care, citing that this is his fault due to him inviting Penny to lunch when they first met her. He then storms out in a rage.
That evening, after Howard and Leonard explain what happened, Penny and Bernadette are dismayed, and explain they had gone without Amy because she was over-enthusiastic and would've been a hindrance to their dress shopping, such as how she talked about various cultural wedding preparations such as getting naked and washing each other. Raj looks interested, getting weird stares from everyone else. Penny is curious how Amy found out. Howard tried to frame Raj, but confesses to accidentally mentioning the photo Bernadette sent him. They never-the-less feel guilty, and visit Amy at her laboratory to apologize. However, their efforts to do so are merely brushed off by Amy, who describes herself as a "tumor" in an otherwise functional brain. Penny is so sickened by looking at the dissected brain on Amy's table that she vomits into the waste basket.
That night, Sheldon gets a call from Amy, who has gotten drunk in a liquor store parking lot, and he and Leonard rush over to help her. She once again attempts to persuade Sheldon to have sex with her at a nearby motel, and embarrasses him by calling him "cuddles". Leonard is actually curious about what it would take for Sheldon to have sex with Amy. Sheldon instead insists that he and Leonard take her home, and Leonard helps her up, finding Amy's "second base". The next day, Penny and Bernadette return to Amy's laboratory, and Bernadette, in an effort to apologize to her once and for all, asks her to be her Maid of Honor. Amy is immediately excited and forgives them at once.
The episode ends with Amy filming a dress shopping trip with Penny and Bernadette as part of the pre-wedding events. She is as over-enthusiastic as they had feared. She agrees that Bernadette is beautiful in a wedding dress, but not "Penny beautiful", which annoys them. Penny is taking a long time so Amy barges into Penny's dressing room with her camera while she's in her underwear, taking a second quick look as she leaves.
- Guest starring:
- Teleplay: Bill Prady, Steven Molaro & Steve Holland
- Story: Chuck Lorre, Eric Kaplan & Tara Hernandez
- The TV Critic: "This was a solid attempt to make Amy a more sympathetic character. She doesn't really seem to learn much by the end of the episode but at least her vulnerability added an extra layer for us to see...Of course the conclusion of the story demonstrated why Amy is a trying friend. She is rude and pushy and made dress shopping more about her than the bride...So often the instincts of the writers are good (Amy needs to be humanized) but their execution isn't right (she remains basically unchanged)."
- The A.V. Club gave this episode a B+
- IMDb user reviews
- Title Reference: Amy feels isolation when her fellow bridal party members go dress shopping without her.
- Chuck Lorre's vanity card.
- This episode was watched by 15.98 million people, with a rating of 5.4 (adults 18-49).
- This episode aired in Canada on November 3, 2011 with 3.762 million viewers and a weekly ranking of #1.
- In the United Kingdom, this episode aired on E4, this episode aired on December 15, 2011 with 1.506 million total viewers and a weekly ranking of #7.
- In Australia, it aired on November 14, 2011 with 1.359 million viewers.
- Episode transcript 
- Leonard wears a "Lunar Cycle" t-shirt by Urban Outfitters (discontinued).
- Bernadette wears the "Impressionist Flowers" dress from Forever21.com.
- Sheldon originally designated the night he spent with Amy for solving the Spacetime Geometry in Higher Spin Gravity and building a Lego Death Star consisting of almost 3,500 pieces, and retailing for about $1,000 for just the pieces, and $2,500+ for a mint sealed box (This is Death Star II, model 10143. Model 10188, a smaller version, goes for around $350).
- Raj understands fashion and dresses, highlighting another one of his feminine characteristics.
- Leonard refers to himself as "single" in this episode, confirming he and Priya have broken up after the events of the previous episode.
- Leonard is seen playing Champion Jockey: G1 Jockey & Gallop Racer on XBox 360 equipped with Kinect. He claimed he is too tall to be a jockey and is afraid of horses.
- Amy had a semester away in Norway and her so-called friends locked her in the sauna with a horny otter.
- Amy had a cousin who died the day before her wedding due to gas inhalation. She was supposed to be the Maid of Honor and the dresses are still unused and available.
- In "The Infestation Hypothesis", Amy claims to know only two songs she can play on her harp, "The Girl From Ipanema" and the theme song to Diff'rent Strokes. She has now added "Everybody Hurts" to her repertoire.
- For someone with an eidetic memory and an IQ of 187, Sheldon did not think to try to reach Amy by telephoning her an idea Leonard gave him after he complained that all his other communication methods have failed. This comment suggests a theory that people who are smarter, have less common sense (or just absent-mindedness).
- Sheldon is someone who detests touching and other forms of physical contact. However, during his counter-offers with Amy at her apartment, he did suggest to stroke her head, give her a neck massage, and later on agreed to cuddle with her. He treats Amy different than any other of his friends and colleagues.
- Sheldon has always emphasized how Amy is not his girlfriend but, when a drunk Amy calls him "Cuddles" at the parking lot, earning a frown from Leonard, Sheldon simply says "Yes, Cuddles, we cuddled. Grow up, Leonard," indicating that he does not care what his friends might say regarding his relationship with Amy.
- First time ever, Leonard is seen imitating Sheldon's knock.
- Amy's claims that Sheldon found "second base" which seems to be the side of her breast.
- Penny is seen wearing the bridesmaid dress style she wore at the wedding, while Bernadette is not wearing the wedding dress she wore at her wedding. Amy is also wearing a different dress.
- Second episode where Sheldon complains about the increasing number of women in his social life. First was "The Gorilla Experiment".
- Second episode where Sheldon talks about an animal with a connection to a main female characters current state, particularly because of his interest relating to the animal itself. First was "The Dead Hooker Juxtaposition".
- Amy: Wait for moi!
- Sheldon: Wha.. you're leaving?
- Amy: Sheldon, sometimes you forget, I'm a lady. And with that comes an estrogen-fueled need to page through thick, glossy magazines that make me hate my body.
- Sheldon: Stand back! While I turn this conversation into a conver-sensation.
- Leonard: How long will it take for Mad Cow disease to kill me?
- Amy: Four, five years.
- Leonard: No, that's not gonna do it.
- Leonard: I would have been a great jockey had I not been too tall.
- Sheldon: Leonard, in your own simple way, you may be the wisest of us all.
- Amy: I was hoping you wouldn't notice. Irene was always a slave to a good bargain, and sadly as it turned out, space heaters.
- Sheldon: She sounds weepy. I don't like weepy, let's go.
- Leonard: She's your friend! Step up. (Leonard imitates Sheldon's knock) (knocks 3x) Amy, (knocks 3x) Amy, (knocks 3x) Amy. Bye. (walks away)
- Sheldon: Where are you going?!
- Leonard: I'm single; I don't need this crap.
- Sheldon: Would you like to talk about it? And keep in mind that 'no' is a perfectly viable answer.
- Amy: Oh, look. It’s Sheldon and little Leonard. Hi, little Leonard.
- Leonard: Hi, Amy.
- Amy: (to Sheldon) Hey, Cuddles.
- Leonard: "Cuddles"?
- Sheldon: Yes, "Cuddles". We cuddled. Grow up, Leonard.
- Leonard: Amy, what are you doing here?
- Amy: Well, I came here to get a bottle of wine like Penny taught me to do when you're sad.
- Leonard: Yeah, but why didn't you go back to your apartment?
- Amy: Didn't you go to high school, Leonard? Parking lots are where all the cool kids hang out. Not that the rat bastards ever invited me.
- Leonard: Maybe we should get you home.
- Amy: Oh, hang on, hang on, hang on. Sheldon, what would it take for you to go into that liquor store, buy a bottle of hooch, take me across the street to that motel, and have your way with me?
- Leonard: Yeah, Sheldon, what would it take?
- Sheldon: I'm begging both of you, please, let's go.
- Leonard: Okay. Come on. Upsy-daisy.
- Amy: Whee! Ooh, finally someone found second base.
- Amy: Sheldon, I’m going to ask you something, and I’d like you to keep an open mind.
- Sheldon: Always.
- Amy: At this moment, I find myself craving human intimacy and physical contact.
- Sheldon: Oh, boy. You know ours is a relationship of the mind.
- Amy: Proposal: one wild night of torrid lovemaking that soothes my soul and inflames my loins.
- Sheldon: Counter proposal: I will gently stroke your head and repeat, "aw, who's a good Amy?"
- Amy: How about this? French kissing, seven minutes in heaven culminating in second base.
- Sheldon: Neck massage, then you get me that beverage.
- Amy: We cuddle. Final offer.
- Sheldon: Very well. Oh, boy. (they cuddle awkwardly)
- Amy: I’m just saying, second base is right there.
- Amy: This is us. Bernadette, you are the analytical, scientific left hemisphere. Penny, you’re the creative, spontaneous right hemisphere. And where’s Amy? She’s right here, the sad little tumor no one wants to go dress shopping with.
- ↑ The Big Bang Theory - The Isolation Permutation (TV Episode 2011) - IMDb
- ↑ The TV Critic's Review
- ↑ The Big Bang Theory: “The Isolation Permutation” - TV Club - The A.V. Club
- ↑ Thursday Final Ratings: 'Big Bang Theory,' 'The X Factor,' 'Parks & Recreation,' 'The Office,' 'Vampire Diaries,' 'Grey's Anatomy' Adjusted Up - Zap2it
- ↑ Top Programs – Total Canada (English) October 31 - November 6, 2011 - BBM Canada
- ↑ BARB via Wikipedia
- ↑ Monday 14 November, 2011 - TV Tonight