Fits of Rage

The neural circuitry of fight and flight.

Fits of Rage

The neural circuitry of fight and flight.

I can't stand the sound of flip-flops.

It's been like this since I was a child and I couldn't tell you where or how it began, but whenever I hear them slapping against the ground, I feel a twinge of anxiety and irritation at the back of my skull.

It isn't something I think about, and it always surprises me. So I was relieved if not less confused to know that I'm not alone in this affliction - many people feel a sudden and visceral unease when they hear certain sounds. These might be noises made by other people chewing, typing, or even sniffling. When this irritation is gripping enough that it turns to panic or rage, it's referred to as "misophonia." Very little is understood about this phenomenon and to psychiatrists, it's somewhat mystifying and unclassifiable. While this may not be a rational phenomenon that's legible in the diagnostic language of psychiatry, neuroscientists know that seemingly inexplicable gut reactions to things we interact with within our environments often lead back to the autonomic nervous system.


Responsible for our most basic "fight or flight" instincts, our autonomic nervous systems are wired to quickly respond to threats and mobilize our bodies to action without consulting the rest of the brain, whose lengthy deliberation processes could cost us our lives. Many curious reactions ingrained in us over hundreds of thousands of years of evolutionary time remain with us even if they've outlived their immediate utility. 

For example, it's common for people to faint when they see blood. And while it may stand to reason that blood loss itself will make us feel faint, the sight of blood on its own sends a signal directly to the parts of our brains associated with fear and with very basic physiological processes like heart rate and blood pressure regulation. This short circuit to our body's control centres exists to protect us. Fainting at the sight of blood might be protective if we need to conserve our resources in an emergency. Extreme discomfort can also be thought of as a protective device, too - we're motivated to get away from whatever is making us uncomfortable as quickly as we can.


Emerging research suggests that certain sounds might operate in some people in the same way that the sight of blood does. According to this work, my aversion to flip flops isn't grounded in any associations or memories I have surrounding the offending footwear, but rather because the sound bypasses my conscious mind and triggers a fight or flight response via the rapid access to the oldest parts of our brains provided by the autonomic nervous system.

 The first stop in the brain as these signals are processed is an unassuming almond-shaped structure called the amygdala, somewhere in the middle of our brains. The amygdala is not only closely yoked to fear, but also to memories of fearful or traumatic events. For people who are especially sensitive to certain sounds, one explanation that has been offered is that the discomfort they feel is the result of an instantaneous engagement of our involuntary nervous systems via the amygdala. Memories can come to be associated with these sounds that reinforce themselves in ways similar to memories of trauma, a mechanism that bears similarities to the way post-traumatic stress disorder is thought to work.

While the microcircuitry of minor irritations that we can mostly consciously suppress is still somewhat mysterious, more recent work in other ancient parts of the brain that act as gatekeepers for our most basic instincts has revealed more dramatic effects. Most of how we understand neuroscience is by either intentionally breaking parts of the brain and seeing what goes awry afterwards, or by observing what happens in people or animals whose brains are damaged in specific ways. In a 2016 study, a group of researchers at NYU found a circuit in the brains of male mice that acts as a switch for attack behaviour. It was known from studies going back as far as the 1920s that severing the connections between certain parts of the brain could induce sudden rage in animals, but the technology to really understand why this was happening wouldn't catch up to the question for almost another century. Using more refined molecular and physiological tools, researchers were able to identify a part of the brain called the lateral septum as the seat of attack behaviour. Particularly aggressive animals tended to have lower activity in this area, and it was shown that activating the lateral septum can dial back the force of attacks or eliminate them completely. In the study conducted at NYU, the researchers used a tool called optogenetics to zoom in on the pathways they were interested in. By injecting a fluorescent protein that responds differently to specific wavelengths of light, scientists are able to flip neural activity off and on like a light switch. When the scientists at NYU directed these optical switches to the lateral septum in male mice and turned the neurons on during an attack on another mouse, they found a dramatic and almost immediate reduction of aggression. What's more, the suddenly docile mice were more curious about the intruder mouse with whom they'd started to pick a fight than the control mice, sniffing or spending time near them without attacking. 


While there are plenty of evolutionary reasons supporting the idea of a fast-acting "fight or flight" system that can help us mobilize our resources to defend ourselves, many studies also support the idea that, at least in the world of mice, some animals are natural bullies. When scientists study reward and motivation in mice, they usually follow a specific set of steps that involves training a mouse to perform a task (such as poking a lever with their nose) by rewarding them with a treat whenever they carry out the task correctly. Usually, these treats take the form of food or even drugs - sugar is the most common and reliable way to train a mouse but researchers have found that chocolate, peanut butter, and even water will also do the job. In a lab setting, mice also have a tendency to try to fight with strange mice who are suddenly allowed access to their space - especially male mice. 

One study found that the opportunity to fight with another mouse might also be motivating. In the study, they found that when given the opportunity to press a lever that let another mouse into their cage, aggressive mice would learn to poke the lever to invite in the intruder mouse as though he were a delicious piece of chocolate. Other studies have supported the idea that this kind of aggression can be rewarding or even pleasurable by looking at the activity in parts of the brain associated with reward. They've consistently found that dopamine - the chemical our brains release that is typically associated with pleasure - increases within these pathways during attacks or even while viewing violent sports.


From a historical standpoint, it makes sense that our brains would be hardwired to reward us for defending our resources or our children in times of scarcity or danger. But as we see over and over again, many of the things we used to be rewarded for to encourage us to engage in behaviours that would ensure our survival are no longer necessary for many. 

We're drawn to sugar and salty, high-fat foods because these were the most energy-dense resources available to our ancestors and it may have been relatively rare to stumble upon them. Now, though, junk foods are ubiquitous in industrialized countries and the daily burden of keeping ourselves alive has been lifted to some extent by technology. A hyperactive fight or flight response is also indispensable for keeping us safe, but we need only look to trauma survivors to find that an exhausting amount of effort must be expended to calm those responses when they no longer serve us.


While I've spent almost every day for the last decade or more thinking about how our brains moderate our reflexes and our motivations, I've never considered aggression in this context. Like all these other reflexive phenomena, though, striking a balance between motivation and control is key. A little bit of frustration or irritation might motivate us to come up with constructive resolutions to conflicts that will improve the way we work and function with the people closest to us. Unchecked, these impulses can be socially and globally ruinous. I believe, though, that the more we understand the mechanics of our nature and behaviours the more we can work to change them in a thoughtful way. One day I may not even mind the sound of flip flops anymore.

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