How scientists discovered the "fear center" of the brainS

Fear is one of the most universally understood human emotions. Every one of us is familiar with the feelings, behaviors, and symptoms engendered by fear — so familiar, in fact, that we can sense it in the voices and actions of our friends and loved ones, and even recognize it in the facial expressions of complete strangers. Yet the neural underpinnings of fear remain something of a mystery.

Having said that, much of what we do know about how our brains process fear boils down to two tiny little lumps of neurons; whether you're a human, a rat, a monkey or a mouse, when it comes to processing fear, the vast majority of research says that the most important parts of your brain are your amygdalae, a pair of almond-shaped clusters of neurons sequestered deep within your medial temporal lobes.

How scientists discovered the "fear center" of the brainS

For over seventy years, studies have suggested that these unassuming little amygdalae actually play an indispensable role in processing brain signals important to perceiving and experiencing fear, but it's taken us up until — well...a few months ago, really — to confirm just how important they really are.

In a paper published in 1939, neuroscientists Heinrich Klüver and Paul Bucy reported that removing the temporal lobes entirely (which, you'll recall, include the amygdalae) led to dramatic behavioral changes in monkeys; the primates were not only more tame and less aggressive than those with intact brains, they also behaved indifferently towards humans whom they had been demonstrably fearful of prior to the surgery. (They also became hypersexual, and developed serious oral fixations, but we'll save that for another post.)

In 1952, a similar study by researcher Lawrence Weiskrantz revealed that removing just the amygdalae (as opposed to hacking out both temporal lobes entirely) led to the same "disappearance" of fear responses.

But even in Weiskrantz's study (and in Klüver & Bucy's experiments, especially), the surgical methods used to remove the amygdalae tended to inflict considerable collateral damage on so-called "fibers of passage" connecting other regions of the brain. In other words, what these early studies couldn't speak to was the possibility that removing one or both amygdalae was disrupting lines of communication between regions of the brain working collaboratively to process emotions like fear.

In the end it took almost half a century for neuroscientists to provide conclusive evidence that many of the behavioral effects observed by Klüver, Bucy, and Weiskrantz could, in fact, be attributed to the amygdala specifically. In 1999, a research team led by neuroscientist Mortimer Mishkin examined the behavioral changes in monkeys that had had their amygdalae targeted by means of a more precise technique — one that allowed researchers to compromise amygdala-function while still preserving the monkeys' fibers of passage.

In doing so, Mishkin and his colleagues arrived at two meaningful conclusions. The first was that some of the behavioral symptoms observed in monkeys with intact fibers were less dramatic than those observed following the imprecise surgical procedures of the past. This suggested that collateral damage was at least partly responsible for some of the behavioral changes previously described.

The second was that the amygdala is, nevertheless, unmistakably crucial for the normal regulation of emotions (and fear, especially) in monkeys. The researchers write:

How scientists discovered the "fear center" of the brain

Relative to controls, monkeys with neurotoxic amygdala lesions [i.e. the new, more precise technique] showed the same array of behavioral changes as those with aspiration lesions [like those performed in ‘39 and ‘54], namely: reduced fear and aggression, increased submission, and excessive manual and oral exploration. Even partial neurotoxic lesions [again, "neurotoxic lesions" here referring to the more precise method of targeting the amygdalae] involving less than two-thirds of the amygdala significantly altered fear...

The significance of the amygdala in the processing of fear likely has to do with its position relative to several key regions of the brain. The amygdalae receive many of their main inputs from the visual, auditory and somatosensory cortices, while its primary outputs are to the hypothalamus, which regulates the production of hormones like adrenaline. One of the main roles of the amygdala is therefore thought to be coupling the perception of a threat via sensory stimuli to a fear-induced fight-or-flight response, initiated in part by the release of hormones like adrenaline, triggered by the amygdala via the hypothalamus.

This, of course, is a vastly simplified explanation of what's going on inside that head of yours every time a horror flick scares the ever-loving crap out of you; in theory, the various inputs and outputs leading to and from your amygdalae are actually involved in several layers of cross-communication that allow for them to regulate your behavior (and vice versa).

And while these assumptions are drawn from conclusions presented in numerous studies, the fact of the matter is that there is still very little experimental evidence that provides direct support for this model. Consider, for example, that the studies we looked at just a few paragraphs up are among the most important in a long line of investigations into the connection between the amygdala and fear in primates, but that when it comes to fear studies in humans, some of the most groundbreaking investigations have actually been conducted pretty recently.

Recent findings made by these human studies have been due in no small part to two major breakthroughs, as pointed out by neuroscientists Andrew Calder, Andrew Lawrence, and Andrew Young in their review, "Neuropsychology of Fear and Loathing," originally published in the journal Nature.

According to the Andrews, the first breakthrough came with the advent of technologies like functional magnetic resonance imaging (fMRI). Imaging technologies like fMRI allowed researchers to measure activity in specific areas of the brain, shedding light on the fear-processing power of the amygdala. (Between 1996 and 2001, no fewer than ten imaging studies reported that neural activity in the amygdalae of people with healthy brains increases significantly during tasks in which test participants view facial expressions of fear; see references 28—34, and 44—46 in "Fear and Loathing" for details.)

How scientists discovered the "fear center" of the brainS

The second breakthrough came with the discovery that certain types of brain injury and psychiatric disorder can screw with a person's ability to recognize human signals of emotion. Studies by Cal Tech neuroscientist Ralph Adolphs, for example, reveal that people with severely damaged or impaired amygdalae have difficulty identifying facial expressions of emotion (happiness, surprise, fear, sadness, disgust and anger, for instance), but have a particularly hard time making sense of the faces that are expressing fear (PDF).

But all these studies look at our ability to perceive fear; are there any studies that actually speak to whether or not our amygdalae actually allow us to experience it?

As a matter of fact there is. But there's only one, and it was published in January of this year.

It's a case study conducted by researchers at The University of Iowa, who for over twenty years have been studying a woman known only as "patient SM." SM suffers from an exceedingly rare genetic condition known as Urbach-Wiethe disease (fewer than 300 cases have been reported since its discovery) that has rendered her amygdalae effectively inoperative; and while SM had participated in plenty of studies in the past, this was the first to examine how she actually experiences fear (or, perhaps more accurately, how she doesn't experience it).

The researchers exposed SM to a laundry list of scary stimuli:

  • Creepy animals? Check; when taken to an exotic pet store and exposed to live snakes and spiders, SM had to be prevented from touching a tarantula that employees were afraid would bite her; voluntarily held a large snake for several minutes (despite having told researchers in the past that she "hates" them and "tries to avoid them"); and reportedly asked a store employee 15 times if she could also hold a more dangerous snake.
  • Haunted house? How about Waverly Hills Sanatorium, commonly referred to as one of the most haunted places on Earth? SM was reported to have been visibly excited to lead a group of strangers through the hospital, which she did without any sign of fear or hesitation.
  • A scary movie? Try ten of them, including Halloween, Se7en, and Silence of the Lambs. Again, SM demonstrated no behavior that might suggest she was afraid.

They even asked her to maintain a computerized "emotion diary." For three months, the diary would randomly ask her to rate her emotional state (by indicating her levels of fear and fifty other emotions) throughout the day. And still, she failed to experience fear.

"Taken together, these findings suggest that the human amygdala is a pivotal area of the brain for triggering a state of fear," said Justin Feinstein, lead author of the study. He continues:

While the patient is able to experience other emotions, such as happiness and sadness, she is unable to feel fear. This suggests that the brain is organized in such a way that a specific brain region — the amygdala — is specialized for processing a specific emotion — fear.

Top image via Arman Zhenikeyev/Shutterstock. Cross-section of brain via . Macaque via headcycle. Emotion Hexagon via Nature