1–30–17, Lefko
Humans brains are unique from animals mostly due to our conscious thought processes, emotions, and interpersonal interaction. This makes it almost impossible to study the gross symptoms of lesions to the brains in animal models (there are some rather crude exceptions, as you’ll see below). Thus, for the most part, we need to rely on actual humans with brain disorders to learn anything. BUT, who’s going to donate their fully functioning brain for us to lesion? Moreover, how do you know where you are going to cut/ablate/otherwise destroy when there are close to no landmarks separating the incredibly fine distributions of control centers in the brain? Now you see the problem.
Because of this, we rely on people who come in with naturally occurring lesions to describe their symptoms and rationalize what is going on (and let me tell you, the early days of the Wild West of neuroscience had some unbelievable stories). With that said I’d like to introduce a semi-ongoing series where I will occasionally discuss the history behind our understanding of some of the most esoteric brain structures, systems, and disorders. Because Double D knows many of these stories from our classes, I will try to keep the really landmark cases to a minimum (plus, as dope as those stories are, they’ve been beaten to death) and explore some of the fringe cases that still leave us scratching our heads.
Let’s start with the limbic system. To orient you, check out the image below
There’s still some argument as to all of the structures that are in the limbic system, but the main ones are the thalamus, hypothalamus, pituitary gland, amygdala, and hippocampus. Broadly speaking, from our current understanding, the limbic system is responsible for the regulation of emotions within the brain (limbic coming from the latin word for limbo, literally the space between the complex conscious cortical regions and the lower automatic functions of the brain). So how did we get to this understanding?
The early days of limbic research really began in the early 1900’s with famous neurosurgeon Harvey Cushing — originally at Hopkins before moving to Harvard. He was known as the eccentrically delightful neurosurgeon so passionate about his studies that he scarcely left work until the last days of his life. You might know Cushing of Cushing’s disease fame, but his really wild work began with the Pituitary gland and his study of things like giantism and dwarfism resulting from pituitary disorders (I highly recommend reading up on this stuff if you’re interested, but it’s outside of the meat of this FF).
After Cushing’s death, research in the field kept plugging along, but most people didn’t realize the implications of what he had begun. It wasn’t until 1937, when James Wenceslaus Papez (rhymes with drapes) — a neuroscientist from Cornell — that we reached a turning point in emotion research. Papez saw calls for a large grant to try to understand emotions and read the underlying implication as current neuroscientists don’t know anything about emotions. Angered by the implicit gg of the US govt., Papez decided to summarize all existing knowledge about emotions in his grant application without realizing that he was the first person to concisely and accurately try to interpret all the previous literature. To put it in Kean’s terms (author of the book I’m reading, see below), “the whole of the paper far exceeded the sum of its parts.” Indeed, most previous work consisted of isolated case reports, but no one had attempted to piece it all together. Papez seminal work from this grant eventually led to the crowning of the Papez limbic circuit which would become his greatest achievement.
Anyway, for all this work, Papez ’twas but a mere mortal, and forgot one of the most important structures in the limbic brain — the amygdala (from the Greek word for “almond” because it’s almond shaped) — which sits in the temporal lobe and contributes to what neuroscientists call the “so what” stream of consciousness. That is, you have “what” and “where” vision streams in your brain which send connections to your amygdala which then partially performs the computations to decide if you should be reacting to something and also passes the info along to regions that decide to what extend and how you react. It’s a very important way station in the progression of an emotional reaction to something. The amygdala is particularly adept at fear responses (this makes sense evolutionarily since a fear response is more important than most other emotional responses in the wild if you are trying to stay alive). We must be careful here, as the amygdala is often referred to as a fear center in the brain, but it actually modulates quite a bit more than that.
This leads me into our first case study — that of a woman named S.M. who suffered Urbach-Wiethe disease at ~10 yrs old. The disease killed amygdala cells and within two years she had two little empty holes where her amygdalae used to be. From that day forward, she never experienced fear. This story becomes entertaining historically, as the rest of her medical life was spent with doctors who devised ever more intricate ways to scare her. In one instance, docs drove her to an exotic pet store to see snakes. In the car ride she kept mentioning that she hated snakes, but as soon as she got there she was absorbed with fascination for the reptiles and kept running around trying to hold them all. She even asked fifteen times if she could hold the venomous ones…
In another attempt to scare her, they took her to an old insane asylum turned haunted house with five other women to compare their reactions. The women were screaming every few seconds while she kept running forward and trying to poke the “monsters” masks to see what they felt like. Another time they took her to a maximum security prison and let her interact with multiple inmates convicted of homicide to see if she would be scared of them lashing out at her. No response.
Okay those experiments sound a bit contrived, she wasn’t really in any danger. What was she like in real life? I point you to the “knife incident.” She was once walking home at night and cut through a public park where a man she described as “drugged out” yelled at her. Without hesitation she approached him and he put a knife to her throat and yelled “I’m gonna cut you bitch.” To which she did not immediately respond, finished listening to the church choir practicing in the distance, and said something about God’s angels protecting her. Apparently the attacker was so weirded out that he let go and ran away while she walked away nonchalantly (and returned the next day). She was also held at gunpoint during a case of domestic abuse and wasn’t scared. Rather, she saw these things as inconveniences and annoyances.
You might be wondering if this was fear-specific, and it turns out it was. Researchers asked her to identify emotions on the faces of people in pictures, and she could identify all except for fear. She was also showed clips of movies and described herself as feeling sad, mirthful, surprised, and disgusted at appropriate times, but never responded during The Shining and The Silence of the Lambs.
Finally, it’s important to know that critics could say she didn’t lack fear, she lacked common sense. The strongest argument against this is that her response was appropriate of someone who was deficient in a fear response. With snakes she wasn’t afraid but they commanded her full attention. Evolutionarily, you would want a situation like this to take up all your attention, even if it doesn’t draw fear.
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That took up a lot more space than I thought it would, so I will leave you with one last limbic foray near and dear to Five Guys’ hearts (s/o hypothaLoomus): sex.
Turns out the Limbic system is intricately involved in sexual regulation, and there’s a pretty ridiculous story for how we figured this out. In the mid-1930’s biologist Heinrich Kluver decided to start experimenting with mescaline (peyote) to study its hallucinogenic properties. While bored out of his mind on vacation in New Hampshire, he gave some mescaline to a farmer’s cow to see what would happen. The cow died (and the farmer was pretty pissed). Curious wtf happened, Kluver took some mescaline himself (the logical follow-up), tripped dicks, and almost died (didn’t see that coming). For some reason, this only increased his fascination, so he continued experiments with monkeys back at his U. Chicago lab.
Through a series of somewhat cryptic experiments, Kluver eventually hypothesized that hallucinations begin in the temporal lobe. He enlisted the help of a neurosurgeon, Paul Bucy, to remove the temporal lobes (including limbic structures) of the monkeys. Unsurprisingly, the experiments failed and the monkeys still got high.
That being said, they noticed some interesting stuff. The monkeys lost the ability to recognize food and developed an oral fixation — that is they wanted to put everything in their mouths and lick it for a bit (nowadays called hyperorality). How did they determine this? They placed peppermints, sunflower seeds, bananas, nails, lint, combs, eggshells, tin foil, cigarette ash, baby rats, feces, and whatever else they found in their cabinets in the monkey cage. Rather than focusing on the treats, the monkeys methodically picked everything up, piece by piece, and licked them.
Okay, so what’s going on? Well, the inability to identify food is a victim of the lost “what stream” components of the visual system (not discussed here), but the hyperorality and hypersexuality are probably losses from the limbic system. Think about it: the limbic system is responsible for tagging things as pleasurable or distasteful and initiating the appropriate response, whether that be approaching, smiling, fighting, etc. Without the limbic system, both bananas and literal shit nuggets looked like potential food. [Kean again]: “…no matter how many times they grabbed lit matches or humped a technician’s leg, they never hesitated to do it again. And if you think that all this failure and futility frustrated the monkeys to no end, you’d be wrong. Because they lacked a limbic system, they never got upset about repeating the same damn mistake over and over. In fact, they never really betrayed any emotions, ever. No joy, no resentment, no anger, no nothing.”
Kluver and Bucy eventually went on to study humans who exhibited similar symptoms, for which they eventually had Kluver-Bucy syndrome named after them. One of the common manifestations of this is “pain asymbolia,” where patients can recognize something should hurt, but don’t actually get worked up about pain because it has no emotional impact.
So what about the whole crazy sex thing in humans? It’s there:
“Kluver-Bucy victims also become hyperoral, and doctors have caught them chomping own on soap, catheters, blankets, flowers, cards, pillows, glass thermometers, and everything else in their hospital rooms. One victim suffocated while trying to swallow an Ace bandage.”
Moreover, seizures that spread to the limbic system can initiate Kluver-Bucy behavior. Specifically it can do anything from increasing sexual appetite to make you a fiend, to depressing libido to Mariana Trench levels. Some epileptics have never had an orgasm in their lives because of this. Others have multiple per day (apparently rabies has a similar effect and can induce spontaneous ejaculations up to 30 times per day — gg sixpeat). Some temporal lobe lesions that induce Kluver-Bucy can change people’s sexual orientiations from straight to gay and vice versa. Others can lead to inappropriate desires, ranging from Zoophilia to coprophilia, pedophilias, and other –philias so unique they don’t have names.
One famous Kluver-Bucy patient was L.E.E., a 38 year old carpenter who, from childhood, fetishized safety pins. “After withdrawing the safety pin from his pocket — the shinier the better — he stared at it with increasing titillation for a minute, then became glassy-eyed. He hummed, sucked his lips, and went rigid; his pupils dilated. It’s unclear if L.E.E. actually climaxed this way, but he didn’t care. He claimed that his shuddering, groaning, mini-seizures actually trumped orgasms, providing much more pleasure.” Apparently his wife almost left him for this because he eventually couldn’t salute the captain during the foreplay, which pissed his wife off. Surgeons eventually had to remove 3 inches of his temporal lobe before he could court the missus again.
L.E.E. was unique in that removing part of the temporal lobe helped his problem without introducing more. Often, the tissue that is removed is responsible for suppressing libido, and without it the patient becomes hornier than a pubescent rabbit.
E,g, One patient had erections that would last several hours, and was ready to go again immediately after ejaculation (b/c fuck the refractory period, amirite). It wasn’t uncommon for spouses to pull neurosurgeons over and ask for a lobectomy themselves so that they could “keep up.” Famously, another 24 year-old patient began begging neighbors, friends, strangers, and even family members for sex. When she was inevitably rejected, she would just start masturbating right then and there (oh good). She was once hospitalized for a seizure and within 30 minutes of checking in she escaped from her room, only to be found under the sheets of an elderly man who had just had a heart attack, her head bobbing up and down. Hilariously, one doctor commented “One person’s syndrome was another’s lucky day.”
TL;DR: Brains are weird, emotions are confusing (also, water is wet), and sex is far too delicate for how we treat it.
This series was inspired by a book I’ve been reading titled “ The Tale of the Dueling Neurosurgeons: The History of the Human Brain as Revealed by True Stories of Trauma, Madness, and Recovery.” Highly recommend checking this one out.
