How dopamine helps you pick your battles

If you want a mouse to learn something quickly, give it a strawberry milkshake.

Behavioural neuroscientists know that mice have a powerful sweet tooth, so it’s common in this kind of research to use saccharin or glucose as a reward. But mice crave strawberry milkshakes so strongly that they’ll work harder for a few sips than for other kinds of sweets. They’ll also make fewer mistakes and complete more trials during cognitive tasks before they give up.

Every mouse has a break point, though. Even when the stakes are as high as a strawberry milkshake.

Mine was during graduate school. I’d been working in my lab for a little over three years and, by many metrics, I was doing well. I was doing work I enjoyed, I’d co-authored a few papers, and I’d reached a dreaded crossroads in the journey of a PhD student: the qualifying exam.

The word “exam” here is misleadingly innocuous because what happens is as follows.

First, you have to corral 5–7 faculty members into the same room for the better part of a day. Identifying this rare bridge across the schedules of a group of academic researchers can take several weeks and is a feat unto itself. When you’ve done this, you boil down the research project you’ve been toiling over for years into a two-hour PowerPoint presentation. After that, it is the job of your committee to turn your research inside out for another full hour. They can, and will, ask you excruciatingly detailed questions about any part of the talk you’ve just given.

Even a stray enzyme hovering in the bottom left-hand corner of your introduction slide. Especially that enzyme. Possibly only that enzyme. So you’d better know exactly what that enzyme does.

You are then asked to leave the room. They talk about you for minutes that feel like hours, and then they summon you back inside to deliver the good news that you’re now “qualified” to advance to PhD candidacy and continue doing what you’ve spent the last several years of your life doing. Or, bad news, you don’t qualify, and you’re asked to leave.

Either way, you are expected to bring enough pastries and coffee for everyone.

In the second case — when you don’t qualify — you might be offered what’s referred to as a “terminal Master’s degree”, which sounds like an incurable disease or an obscure, elaborate kind of punishment. For a lot of people in academia, it sort of is. Especially when it’s your decision.

This was the decision I made.

I decided to go to graduate school because I loved science, and no other career option made sense to me.

But there was a point at which everything about academia that wasn’t science — relentless pressure to publish or perish, eviscerating competition, and an underlying assumption that if you didn’t live in the lab you didn’t deserve to be there at all — overwhelmed me. Many people can tread water in this environment, even thrive in it. But around the time of my qualifying exam, I decided that what I would certainly have to give up wasn’t worth what I could possibly gain.

So, how do we know when to quit? From the moment we learn to speak, we’re pressed to achieve, to succeed, to discern a goal-line at some distant future point and spend every moment in between working doggedly toward it. But when do we learn that sometimes it’s better not to try, or at least not to try so hard?

When we’re toddlers, we start by observing the people around us. A set of experiments published recently in Nature Human Behaviour gave babies a simple job: pull on a rope to get a toy out of a plastic box. Before it was their turn to try, though, they were separated into groups and allowed to watch a grown-up do it first, to varying degrees of success.

Then, the toddlers were given the same task, with the catch that the whole assembly was fixed in such a way that no matter how hard they tried, they could never get the toy.

Aside from its utility as a tidy metaphor for my abbreviated PhD career, we can actually learn something valuable from this task about how our expectations inform our efforts. If a child had first seen an adult get the toy easily, she’d spend less and less time trying over several rounds of the task, opting instead to ask for help. A similar drop-off in trying time happened when she’d seen a grown-up try very hard and fail, but in this case she wouldn’t bother to ask for help. If she thought the task should be very easy based on what she observed, she’d also pull on the rope harder. This wasn’t so if she thought it couldn’t be done.

The group of babies in the middle, though, saw an adult get the toy out of the box only after they’d worked at it for a while. When they knew it was a challenge but that ultimately they should be able to do it themselves, they pulled a little harder for each successive round, trying for the same amount of time without asking for help.

The researchers also tracked the babies’ emotional states and they found the highest levels of frustration in the babies who thought the task should be easy but realised it wasn’t. The babies who thought it should be impossible actually weren’t visibly frustrated until several rounds of trials had passed. They weren’t upset by their failure because they had no reason to believe success was an option.

Dopamine has come to be synonymous with euphoria and addiction. It’s associated with the high-highs of bipolar disorder and the development of out-of-character, impulsive behaviors in Parkinson’s patients who receive levodopa treatment.

At first glance, it’s easy to dismiss dopamine as the keg-standing frat boy of the monoaminergic neurotransmitters. At heart, though, it’s a hard-working economist and statistician, poring over all of your past experiences and performing careful risk-versus-reward calculations to help you make the best decisions in the future.

Dopamine levels track motivation, and the probability that an action will be completed. These don’t necessarily need to be indulgent, hedonistic actions like binge drinking or gambling or doing drugs, either; rather, it’s any action that might be associated with a novel, possibly rewarding outcome. This is how we acquire new skills, learn new languages, or study for exams: our brains have decided that some things are more worthwhile than others, and we move in the direction of those things.

This line of reasoning has been applied to the dramatic slowing or cessation of voluntary movement in Parkinson’s patients. It isn’t necessarily that they can’t move, it’s more that according to their dopamine neurons, there isn’t any point.

Each of our actions is weighted by its costs and benefits. Some of these are literal no-brainers; protective reflexes that bypass your higher processing centres and go straight through your spinal cord and basal ganglia — the base of your brain, where automatic programs needed for everyday survival are generated and relayed. Others are more subtle, and they’re heavily informed by your individual experience — wearing grooves in your brain that are unique to you; dependent on where you go, with whom you interact, and how those experiences play out.

One thing that can tip the scales in this dopaminergic cost/benefit calculus is stress. In humans, stress correlates with higher levels of the hormone cortisol. The rodent equivalent is called corticosterone, and it’s often given to mice to mimic human anxiety or chronic stress.

When a mouse is stressed out, it avoids other mice, it won’t explore its surroundings, and even if it’s really hungry it won’t venture out to get a piece of food if has to go into an unfamiliar space to obtain it. It will also take longer to learn a new task, and if it’s required to make an effort to get a reward, it won’t work as hard as its stress-free peers.

The same phenomenon is is seen in mouse models of Huntington’s disease.

In clinical terms, Huntington’s is a “rare and aggressive neurodegenerative disease that causes debilitating motor and cognitive decline in its end stages”.

What this means for patients is that, as the disease progresses, they lose control of their movement and speech, as well as starting to have trouble with memory and comprehension. (These are features common to both Alzheimer’s and Parkinson’s disease too).

In the very early stages, though, it starts with subtle changes in mood and motivation. When dopamine levels in the brains of mice were tracked, dopamine went up in healthy controls when they understood they’d get a larger reward if they worked harder for it; they might have to wait longer or press a lever a few more times, but the reward would be larger too. And successively higher dopamine levels were seen in these cases, indicating that their brains assigned higher reward-values to whatever that extra effort resulted in.

In the Huntington’s mice, dopamine levels remained consistently low across varying levels of reward. Which isn’t to say they didn’t still enjoy sweets just as much as the other mice — they preferred saccharin and sucrose just as strongly in preference tests and ate just as much sugar when they were given free access to it. As soon as the stakes got higher, though, and they were required to put more and more effort into getting their sugar fixes, the Huntington’s mice lost their motivation.

What would otherwise have been a coveted, delicious treat somehow wasn’t worth it anymore.

It took a lot to get us to where we are as a species. Keeping a few individuals alive long enough to pass on their genes was a high enough hurdle to clear in the beginning. Then, the challenge became keeping enough groups of people alive for long enough to bring future generations through their lives, to show them how not to die. And in order for someone not to die, they need to feel something about the things that keep them alive.

In rare and sought after cases, that feeling might feel really good. At a minimum, though, they just need to feel compelled.

This is what dopamine does: it pulls us toward things that have the potential to be new and exciting ways to stay alive. But it can also lead us to our break points, preventing us from endlessly pressing a lever when we’re getting nothing in return. We all start out with an idea of the life we want for ourselves, and it’s easy to feel pressure from every angle to pick a path to that idea and follow it in a straight line.

Sometimes the more difficult task, though, can be knowing when to change course, and learning not to linger so long that you get stuck.