Matt Perryman Matt Perryman

The Cortical Lottery: Dopamine and the Activity Set-point [Research Review]

Years ago in one of my criminology classes, the professor introduced us to various theories on social deviance. Criminologists want to know what makes people act up and steal, or rob you in the street for crack, or stab their neighbors in the face. That’s social deviance. Lots of theories have come and gone over the years, thanks to the mysterious wiles and real difficulties of doing quality sociological research.

Lots of ideas came out of the literature, ideas on social strife, class struggle, even plain old boredom. One of these in particular stuck with me over the years, thanks to my budding interest in cognitive neuroscience. The theory goes that some people are natural stimulus-seekers. For whatever reason, this group lacks something in their brains, or they have some dysfunction that leaves them feeling under-stimulated, and this leaves them with an itch. These people are always in search of a fix, always looking for the next hit of neurochemical reward, and as a consequence they’re more likely to go out and get mixed up in naughty things like drugs, sex, and, you guessed it, crime.

At the time, I didn’t think much of the idea. Not because I don’t agree with it, but I didn’t have nearly the interest in behavioral psychology and neuroscience back then. With my current investigations into the neurological factors behind exercise performance, the concept of the stimulus-seeker brain-type stands out. To understand why, we need to look at how neurological activity creates behavior.

I recently finished Jonathan Haidt’s book The Happiness Hypothesis: Finding Modern Truth in Ancient Wisdom. I found it a brilliant read, but I didn’t wind up doing a full review on it because I didn’t have a clear way to relate it to exercise or performance. As you could imagine from the title, the book examines the concept of happiness–where does it arise in the brain, what causes it, and what are the circumstances that maximize that feeling of ambiguous bliss? An interesting topic, but there was no direct application to exercise, minus the vague connection to neuropsychology.

What stuck with me from Haidt’s argument, and where I’m going to start drawing perhaps fanciful connections, is what he calls the ‘happiness set-point’. For those of you who follow the research on body composition and obesity, the term set-point will be familiar. In that setting, the set-point is a level of body fat (and total body mass, depending on how you look at it) that your body will tend to return to, regardless of any changes you make to your diet or activity level. The set-point is a function of physiological mechanisms—such as how well you build muscle or store and burn fat, among others—but also central mechanisms in the brain which regulate bodily processes and behaviors. It’s those central systems that are of interest, since they regulate the behavior of muscle, fat, and, unsurprisingly, you (you in the sense of personal identity).

It’s like the body has a built-in thermostat. If you’ve ever dieted down below your set-point, you’ll know it. You’re always hungry on a diet, but at levels of leanness lying outside the programmed parameters, hunger changes. It becomes more visceral. You can out-willpower this drive, but it’s not easy. The body wins sooner or later, and you eat back to a level of fat it’s happy with.

This is homeostasis, the organism’s striving for stability, and we need that process to stay alive. Most everything in the body has a set-point of some kind. Drawing on research into the neuropsychology of happiness, Haidt suggests that human beings have genetically-governed happiness set-points. Events that make us extremely happy—such as winning the lottery—or extremely sad—losing our house in a fire—tend to balance out in the long run. Changes in happiness are temporary; given time, we tend to return to our baseline level of happiness, called our affective style. Identical twins demonstrate identical affective styles, even when adopted into entirely different families. Psychologically, we’re on a treadmill. We can make small gains, or fall slightly behind, but we always tend to stay more or less in place.

In case anyone’s wondering, this isn’t New Age kookery he drummed up. He’s drawing on verifiable peer-reviewed research to make these conclusions, which you can see for yourself on PubMed by searching for ‘hedonic treadmill’ and ‘set point theory of well-being’.

Since happiness is an emotional state dictated by specific flavors of neurons in specific regions of the brain, it follows that happiness would be a heritable, genetically-regulated trait. Haidt calls this ‘the cortical lottery’. Your baseline happiness and affective style are determined by inherited biological factors, passed down from your parents. Fascinating stuff, but as I said, there’s not really a direct connection to exercise and performance.

I was recently perusing my database of research papers and stumbled across a paper that deserved a review. Not only does it tie in with The Happiness Hypothesis (in a way that will shortly become clear), but it’s right at the crossroads between central fatigue and the recent behavioral-cognitive neuroscience posts I’ve been making. This one’s a freebie in Pubmed Central, if you want to read along at home.

Approach & Withdraw

A little neurochemistry can help put things in perspective before getting into the paper. Human behavior is dominated by two fundamental signals. Depending on the stimulus, we either want to Approach or Withdraw, feelings which are mediated by so-called pleasure-reward signals which originate from the mesolimbic dopamine system. Dopamine makes us want food, sex, and drugs, and it gives us both the psychological motivation and the physical drive to go and get these things. Lack of stimulation, or inhibitory signals coming from other parts of the brain, generate feelings of apathy, fear, or disgust. These are the Withdraw behaviors, encompassing fatigue, lethargy, anxiety, fear, and depression. Mood, memory, learning and related cognitive functions are closely related to the Withdraw behaviors, which is why memories tend to form around fear and other intense emotional experiences.

As you can see in the picture, these competing Approach and Withdraw systems are found in specific brain regions, made up of circuits that come in either dopamine or serotonin flavors. In past discussions of central fatigue and motor drive, I’ve mentioned ambiguous brain regions that govern both mood and motivation, along with your ability to Do Things (governed by the nigrostriatal system, sibling of the reward system). These would be those regions.

How you're wired
Dopamine & Serotonin Networks in the Brain

The red and blue networks reach into the frontal cortex, which is where you hang out — you meaning the context of your identity and sense of self. The frontal cortex is responsible for creating that sensation by integrating signals from other brain regions. When you feel hungry or tired or scared or excited, you become aware of this on a conscious level thanks to the hidden functions of these competing networks (the red & blue lines).

The Approach and Withdraw systems integrate feedback from all over the body. Muscle, fat, the enteric (or gastro-intestinal) system, and the immune system are all involved in major cross-talk with the brain. When you feel tired during exercise, that’s partly due to feedback from your muscles and signals of low energy. When you get sick and feel bad, that’s signaled by chemical messengers from your immune cells.

To me, this is fascinating simply for the conclusion we can draw: The neurological factors that influence (and largely determine) your behavior also influence your physical responses to the environment. The same factors that make you moody or euphoric or tired or happy also dictate how you’ll respond physically to any given situation. And there, good people, is our link to exercise.

Rats Don’t Smoke

The above-referenced paper is a thorough review of the dopaminergic circuitry in our brains, which is known to drive reward-seeking behavior and, when faulty, can lead to obsessive and addictive behaviors.

The authors expand on that role and relate the pleasure-reward circuitry to voluntary activity — that is, the same mechanisms that make us go after feel-good stimulus also determine how much exercise we do (or don’t, as the case may be). For reference, the endocannabinoid system I discussed a few weeks back is a strong activator of the pleasure-reward circuitry. The authors note that “a role of the dopamine system in regulating motivation for physical activity can be implied from studies of addiction.”

They continue: “It has been hypothesized that people who are addicted to such things as risky behavior, drugs, and gambling may have genetic differences in their dopamine system that predispose them to such behavior”.

These conclusions are based on rat studies, looking at the varied responses to drugs in rats expressing degrees of sensitivity to dopamine. Rats with low expression of the dopamine receptor experience feelings of pleasure when given psychoactive drugs, while those rats with high levels experience aversion, suggesting that the two types of dopamine receptors and the dopamine transporter are involved in addictive behaviors.

This responsiveness probably varies across other reward-seeking behaviors, and sure enough, genes linked to dopamine function also predict the amount of voluntary exercise these rats get. The authors suggest that the dopaminergic system mediates the pleasure-reward feelings of exercise, explaining why some of us move a lot and others don’t.

The ‘activity set-point’ (my term, not theirs) is linked with feeding behavior, in that it regulates our motivation for physical activity to get food. They point to the so-called ‘drive for activity’ that sometimes happens in anorexia patients, noting that these people might exercise excessively to relieve the ‘anhedonic state’ created by malnutrition (anhedonia being the state where you can’t feel pleasure, or the pleasure response is blunted). Intense exercise increases dopamine reward signals, so exercise creates that fix in place of food. From my point of view, this is illuminating given the number of women who seem driven to exercise themselves into the ground while dieting, even without a real eating disorder.

It won’t surprise you to hear that overweight and obese people also demonstrate changes in these regions, which increase food intake compared to people of normal weight.

These dopamine circuits are involved with any motivated behavior, whether you’re after food, sex, drugs, or the blackjack tables. And yes, exercise too.

Seekers & Responders

The discussion of baseline activity levels in mice is where the paper gets juicy. Several studies, along the lines of the drug-responder rats, show that mice with a high activity level, based on voluntary running behavior (exercise for mice), also show high tolerance to dopamine-stimulating drugs like amphetamine and bromocriptine.

The Low Activity (LA) mice, with normally-functioning dopamine circuits, don’t need much stimulation. A little goes a long way. As for the High Activity (HA) mice, they had low levels of dopamine at baseline, so they could hit amphetamines all day long — and not only did they have a higher tolerance, but they were more likely to seek out the drugs and get addicted to them.

Much like the simulus-seeking criminals my professors told us about, these rats were dopamine-deficient and looking to fill a need for excitement. These rats not only engaged in more risky behavior, but they were more active on their own terms. They need the novel sensation in order to feel good. Drugs, exercise, food, it’s all the same. They have powerful appetites that need to be sated.

Like the happiness set-point, it appears mammal brains also have a set-point for voluntary activity, which is itself related to sensation-seeking and, perhaps, risk-taking behavior. High-responders with an affinity for sensation and novelty tend to be more active, as they’re making up for a biological deficiency of dopamine. The downside is that they’re always looking for novelty, so same sensation is likely to become boring, or just inadequate, with repeated exposures. Low dopamine activity means high tolerance for behaviors that would be excessive in low-responders — like regular, strenuous exercise.

Low-responders are content. With normal dopamine levels, they’re left feeling good. With a much lower need for — and tolerance of — voluntary physical activity, they don’t need to be so active and engaged all the time. In fact, being active all the time might wear them out.

While the motor control areas of the brain are separate from the reward and motivational areas, the two regions are connected and don’t act in isolation. Numerous studies show an “overlap between the motivational aspects and motor control aspects of brain neurology, with the dopamine system mediating both portions”.

Over the years, I’ve noticed that some athletic types, whether recreational or competitive, seem to like doing ‘more’, while others like doing ‘less’. This brings to mind a whole spectrum of activity levels, from endurance athletes and exercise-addicted dieters who can rack up hour upon hour of weekly exercise, to the overtraining-fearful of the Hardgainer school who might hit two hours a week.

Some people like doing more, others like doing less. Even in the middle ground of regularly-active and successful strength training people, you find those who are very conservative in the amount of time they spend in the gym, and others who would live there if they could make it happen. Traditional views of strength training push for gym-intensity, going in and working hard, straining, and leaving it all there, while going home to rest for a week.

People that fit that latter profile I call ‘intensity responders’. They like to come in, hit some heavy grinding sets, and call it a day. To these people, training a muscle or lift twice a week is high frequency. Once a week is more the norm, and even lower frequency, in the range of 10-14 days for some lifts, isn’t out of the question. Most importantly, these guys can make it work and thrive on this kind of training for most of their career.

The other group is ‘volume responders’. These people can train all the time, but they burn out fast if you demand too much intensity from them. Hard-straining grinder sets, the bread and butter of the intensity responder, must be limited to small doses — too much will floor them. Heavy but fast and explosive movements are the volume responder’s mainstay. Traditional strength-building movements like squats and deadlifts can be done at moderately high percentages, but only as long as speed remains high. Olympic lifts, sled pulling, and other fast, concentric-dominant exercises are the rule, and all can be done heavy and often.

A difference in neurochemistry, in the dopamine and serotonin networks, explains this nicely. Romain Meeusen, a researcher at Vrije University in Belgium, has done extensive research on the role of dopamine and serotonin networks in fatigue and overtraining. A review paper published in 2007 summarizes much of the contemporary knowledge, and provides us with a sciency explanation for the differences in responder types.

Central fatigue happens when serotonin levels increase relative to dopamine levels. Exercise causes changes in neurotransmitter levels that wind up causing the loss of neural drive:

The central fatigue hypothesis is based on the assumption that during prolonged exercise the synthesis and metabolism of central monoamines—in particular 5-HT, DA, and NA—are influenced. It was first suggested by Newsholme et al. (1987) that during prolonged exercise increased brain serotonergic activity may augment lethargy and loss of drive, resulting in a reduction in motor unit recruitment. This, in turn, may influence the physical and mental efficiency of the exercising individual, factors which could be regarded as central fatigue. The serotonergic system has been suggested as an important modulator of mood, emotion, sleep, and appetite and thus has been implicated in the control of numerous behavioral and physiological functions (Meeusen et al. 2006b).

Davis and Bailey (1997) developed Newsholme’s original hypothesis. This revised central fatigue hypothesis suggests that an increase in the brain content ratio of 5-HT to DA is associated with feelings of tiredness and lethargy, accelerating the onset of fatigue, whereas a low ratio favors improved performance through the maintenance of motivation and arousal. Given the strong relationship between alterations in neurotransmitters and neuromodulators and an individual’s mood, it is likely that the sense of effort and its relationship with the willingness to start and continue exercise can be significantly influenced by the central nervous system.

Genetic differences in the basal levels of and sensitivity to these neurotransmitters–and in exercise-induced changes to those circuits–are a likely candidate for differences between intensity and volume responders. The dopamine system regulates how much you want a thing, not how much you like it, which explains why I can hate squatting and Prowler-sprints but still want to go do them (and how, on other days, you can’t get me into the gym).

Intriguingly, the anti-smoking anti-depressant drug buproprion, sold under the trade-names Zyban and Wellbutrin, influences tolerance to exercise under conditions of heat. Big deal you say, but what’s interesting is that Zyban increases tolerance to a range of fatigue signals–that is, activity in the brain winds itself down due to signals from your body which say ‘too hot’. Mice and humans alike ignore those signals with a dose of Zyban, which means that the increased dopamine function made them more fatigue-resistant (and potentially subject to heat stroke, which makes this kind of thing even more risky than normal training). This may not generalize to other forms of fatigue, and evidence so far suggests that it doesn’t, but it’s an interesting piece of data on how the body affects the brain.

As for our criminals? Science is still debating over that one, but there’s lots of evidence emerging on the nature of the psychopath, the amoral, unemotional, logic-without-feeling type of person who knows right from wrong, but doesn’t feel it intuitively as most of us do. The psychopath learns to mimic social conventions out of necessity, not empathy, though a lack of impulse control can lead to violence. These people radiate weird, and wonder of wonders, this is due to a difference in brain function. The amygdala, a fear-generating region in the mesolimbic system, and the orbito-frontal cortex, which is part of your ‘rational brain’ responsible for impulse control, both show faulty behavior in the psychopath.

Sensation-seeking and the mesolimbic system probably aren’t the universal theory of crime the criminologists would like to have, but those factors do go a long way towards describing why some people are assholes, criminality aside.

I have a lot more to say on this subject, particularly as it relates to the mindfulness concept and the neuroplasticity concept, and as all of these relate to athletic training. Knab and Lightfoot note that exercise can alleviate symptoms of depression, and that exercise is often prescribed for that very purpose. According to them, exercise increases the production of neurotransmitters and leads to improvements in neural plasticity, cognitive function, learning, and mood. Lots of neurological evidence suggests a strong connection between motor learning and physical activity and the BDNF-stimulated growth of serotonin neurons in the hippocampus, which influences memory formation and sense of well-being. The natural state of your dopamine system influences how much activity you’ll do, but exercising modulates the dopamine system–as with depression and your affective style, it’s not so simple as wringing your hands, saying ‘genetics’, and end of discussion. You can, and should, take steps to train these neurological factors, with exercise and with measures to improve psychological well-being.

Haidt suggests that much of our inner turmoil exists because of conflicts between our emotional minds — the Elephant — and our rational minds, the Rider (a metaphor reused in Switch by the Heath brothers). The Elephant wants to smoke and drink and fight. The Rider likes to be think things through and be indecisive and anxious. But the Rider, far from being an autonomous rational being, is also a slave to the Elephant’s whims, often working as the hype-man to rationalize our unconscious, emotional decisions. Happiness results when you can synchronize the emotional with the rational and the social.

I think we can use cognitive behavioral therapy and mindfulness training and similar domains of introspection to change the way our bodies respond to different kinds of stress, including exercise. I’m strongly leaning towards the idea of changing our degree of responsiveness and our ‘activity set-point’ by using these methods, and perhaps chemical methods to those so inclined. Similar changes happen in depression patients, confirmed in clinical settings, with observed positive-feedback and neural-rewiring mechanisms in play. The placebo effect works even when we know it’s a placebo. Change starts in our thoughts and behaviors, filters down to changes in the brain, and ultimately changes how we can respond to stress. The brain influences thought, but thought influences the brain more profoundly than we’re led to believe.

Bruce McEwen, neuroendocrinologist and stress researcher at Rockefeller University, has investigated the central factors of stress response and demonstrated how it’s all in the mind — body affects thought and changes behavior, and in turn these changes filter down into a stress response in the body. One cause–say an illness or stressful life-event–leads to a self-reinforcing spiral of ‘adrenal fatigue’ and chronic fatigue symptoms.

But that can work both ways. If we can stay on top of the psychological responses, we can get the upper hand on the physiological. I’d like to capitalize on that.

Knab AM, & Lightfoot JT (2010). Does the difference between physically active and couch potato lie in the dopamine system? International journal of biological sciences, 6 (2), 133-50 PMID: 20224735

Meeusen, R., Watson, P., Hasegawa, H., Roelands, B., & Piacentini, M. (2007). Brain neurotransmitters in fatigue and overtraining Applied Physiology, Nutrition, and Metabolism, 32 (5), 857-864 DOI: 10.1139/H07-080