#159 - Why Thinking Makes You Tired

0:01Hi there, and welcome back to the podcast. It's Matt here. Today, we're going to be talking about chairs, specifically desk chairs, chairs with a seat and a back that you can sit on whilst you do your work at a desk or a kitchen table. Their sole job is to keep your body still whilst you do something else. This makes them somewhat accidentally excellent scientific instruments, Sit in one whilst doing some cognitively demanding task, balancing the books, writing a tricky report, doing an exam. And when you finally get up after a few hours, you'll probably feel pretty knackered. The chair, however, will have faithfully logged the fact that you haven't lifted anything, carried anything or done anything particularly strenuous.

0:53So why are you so tired? I used to assume that mental work tires you because your brain uses up all of its energy. It's not just an oversimplification. It's flat out wrong. The true answer is much weirder and less certain than I realized. The problem is that tiredness is like the word bank. There are two quite distinct things that we lump together under the term tiredness. One is sleepiness and the other is fatigue. They have different causes and are measured differently, but both can be encompassed by the word tired. The difference is important enough that you can go to a sleep disorder clinic complaining about feeling tired all of the time, but not feeling sleepy.

1:38There was a multi-site sleep disorder study of 606 patients in which fatigue and sleepiness were measured using different standard scales. They found that the two conditions correlated, but only moderately, with a correlation of about a third. Different, but related. Depression, as it happens, was the single best predictor of fatigue in that study. It did more of the explaining than any other factor they measured. But it was a poor predictor of sleepiness. Imagine you're driving in the city. There's lots going on, so your attention is constantly being grabbed by the environment. Now imagine you're driving on the motorway.

2:20There's less going on. So your attention isn't being grabbed by the environment as much. And the less going on, the less your attention is being grabbed. If you were to perform a vigilance task where you had to remain alert for a target stimulus, your performance would decrease the longer you performed it. Whether that decline is steeper for dull, undemanding tasks or for demanding ones is, believe it or not, still argued over. One camp blames monotony, the other has evidence that keeping watch is hard mental work, and that the harder the watch, the steeper the decline. Vigilant attention is what we call the ability to remain attentive during boring and repetitive tasks.

3:05If you were to give people a break during a vigilance task and randomly allocate them to continue the task, perform a different task, or just rest. Vigilance would be best after rest, and worse after continuing the task. A rest break can reverse the decline, at least for a while. In one study, the first break did, but a second one later in the task didn't. And whether very brief switches to another task, a few seconds here and there, do any good, is disputed. One study found they kept people focused, but the largest test, with nearly 500 people, found they made no difference at all. Then comes the solution that many of us turn to in the face of a repetitive task.

3:51Caffeine. Caffeine is an adenosine receptor antagonist, meaning it sits in the receptors adenosine would normally use and blocks them without switching them on itself. And blocking one particular type of adenosine receptor appears to be what gives it its wake-promoting kick. That's been shown cleanly in mice, and the human evidence points the same way. Think of adenosine as a hand resting on a brake lever. Caffeine does not supply the car with petrol. It lifts the hand off the lever, which raises a question I am going to leave open for most of this episode. Adenosine is the sleepiness currency.

4:32It is the molecule behind sleep pressure. So if caffeine works on sleepiness, what exactly is it doing for the other kind of tired? There are two parts to the brain's energy bill. The first is its resting energy use, the energy it uses just to keep on ticking. The second is the extra energy it uses when it is activated. Above and beyond its resting use. The brain's resting energy use is extraordinarily high. Although the brain represents only about 2 % of total body weight in the average adult, it accounts for about 20 % of the body's total energy usage, some 10 times the level you'd expect based on its weight alone.

5:18By contrast, the extra energy the brain uses when activated, the bit you might intuitively associate with mental effort, is quite small, often less than 5 % above its resting levels. Most of the brain's energy budget, around 80%, goes on powering the electrical activity of its neurons and recycling its major neurotransmitters, even when it's apparently doing nothing. When people look at brain scans in which different areas light up as different tasks are performed, it's tempting to think of these activations as comparable to switching on lights in different rooms of an otherwise dark house. But in reality, the brain is already abuzz with activity when at rest, and task-related activations represent only subtle changes in this activity.

6:12It's more like switching on a few extra lights in an already brightly lit house. So although the brain does use energy when thinking hard, this is unlikely to be the source of mental fatigue, and hard thinking is unlikely to be much use as a weight loss strategy, sadly for those of us hoping that it might be. So if mental fatigue isn't due to running out of fuel, could it be down to building up waste products, not an empty fuel tank, but a full ashtray? Advances in neuroscience have made it possible to test this possibility more directly, using a technique akin to dipping a chemical dipstick into a small region of brain to directly measure levels of different molecules while people are thinking.

6:59In one such study, glutamate, a chemical transmitter in the brain, was found to increase by 2.7 % in a region of prefrontal cortex, while 16 healthy adults performed a mentally demanding task that taxed their working memories compared to when they were simply staring quietly at a screen. That was a few minutes of hard thinking. Two more recent studies, both from the same lab in Paris, asked what happens over a whole working day. Both used a similar trick. One group spent a bit over six hours doing hard versions of memory and task switching exercises, while control groups had an easier day for the same length of time.

7:44And every so often, everyone was asked to make small economic choices. In the first study, published in 2016, 58 people took part, 29 on the hard tasks, 12 on easy versions of the same tasks, and 16 who mostly read or played video games between test sessions. The choice was always the same kind, a smaller reward now or a bigger one later. A subset from the hard group and the resting group were scanned with fMRI at the start, middle and end of the day. As the day wore on, the hard task group became steadily more impulsive, going for the immediate reward more often. The control groups didn't, and in the hard tusk group only, activity in a patch of lateral prefrontal cortex, a region recruited by both the hard tusks and the choices, dropped across the day.

8:40A statistical comparison of models suggested that the drop in prefrontal activity was what drove the shift in choices rather than the two simply changing side by side. The second study, published in 2022, ran the same day-long protocol with 40 people, 24 on the hard tasks, 16 on the easy ones, and added choices about effort and risk to the mix. But it swapped the FMRI for magnetic resonance spectroscopy, the chemical dipstick I mentioned, dipped into the same prefrontal region three times across the day. Two things happened in the hard group and not the easy group. First, their choices drifted towards the low-cost option, and their pupils dilated less and less while they deliberated, a sign, the researchers argued, that less effort was going into each decision.

9:35Second, by the end of the day, they had more glutamate, a chemical associated with brain cell activation, in that prefrontal region than the easy group did, and glutamate was moving about more freely there, which is what you'd expect if more of it were sitting outside the cells. And this wasn't a whole brain effect. In the visual cortex, which had been watching the same stream of letters in both groups all day, there was no difference at all. Glutamate is interesting because, according to one theory, it builds up as a byproduct of brain cell activation. and, since too much of it outside the cells does harm, has to be kept in check.

10:14And the researcher's idea is that the brain does this by making the hard-working region more expensive to switch on. The build-up and clearing of glutamate may therefore be a significant factor in the costliness of brain activation, and consequently in fatigue. Now, before I go any further, it's important to note that this theory of glutamate build-up and its subsequent costly cleanup is just that, a theory. It's an interesting one, but it's still speculative. It hasn't been proven, and it's possible that glutamate levels rise for other reasons. One published commentary has argued from how glutamate is distributed inside and outside cells that a rise of this size can't be built up outside the cells at all.

11:00Still, glutamate buildup as a potential source of fatigue is intriguing enough to warrant further investigation. But what I really want to emphasize here is this. In the second of those studies, pupil dilation, an externally observable indicator of brain activity, seemed to index the amount of effort going into each decision. This is interesting because pupil dilation has long been known to increase with the amount of information being held in short-term memory and decrease again as that information is retrieved, with the rate of dilation and contraction dependent on task difficulty. More recent studies have suggested that pupil dilation doesn't just track task difficulty, but actually indexes the degree of cognitive control being exerted.

11:52So, with appropriate controls, for instance, keeping the level of ambient light constant, pupil dilation can give you a pretty good idea of how much cognitive control someone is exerting without needing to stick them in an fmri scanner or measure the glutamate levels in their brains and that ladies and gentlemen is where things get really interesting

12:19a partner for today's episode is ag1 i've been using ag1 for quite some time now and just for the record, I buy it myself to stay away from any of those trappings of free product. AG1 has just released the new formulation, which is AG1 Next Gen. It's still one scoop once a day, but now comes with many upgraded probiotics, plus additional vitamins and minerals. I also explored their four human clinical trials to prove out their efficacy, with the data showing a marked boost in healthy gut bacteria. And that's the thing. I appreciate how AG1 keeps adapting to new scientific findings. They have made many formula changes over the years, and each new iteration keeps it at the cutting edge of this space.

13:10As I've mentioned, I began my AG1 journey over four years ago. Any company that holds their scientific rigor to the flames of clinical trials means a lot to me. So subscribe today to try the next gen of AG1. If you use the following link, you'll also get a free bottle of AGD 3K2, as well as an AG1 welcome kit and five of the upgraded AG1 travel packs with your first order. So make sure to check out drinkag1.com slash mattwalker. That's drinkag1.com slash mattwalker.

13:53The story I told you earlier about chemicals building up in your brain isn't as straightforward as I made it sound. Glutamate doesn't sit around. It's mopped up from the gaps between cells almost as soon as it's released and recycled on the spot. So a slow buildup over hours was never going to be an easy thing to see. And the researchers' own numbers bear that out. They measured glutamate three times across the day, not just at the end, and what they saw in the hard task group wasn't a steady climb so much as a level that held or crept up slightly while the easy task groups drifted down. The two groups were different by the end of the day, but a good part of that was what happened in the easy group.

14:39Interestingly, as people got mentally fatigued, they made lower and lower cost decisions, and that shift lined up with how freely glutamate was moving in the prefrontal region, but not statistically with the amount of glutamate itself. Two more things worth knowing. Both of those day-long studies come from the same lab, and nobody else has yet repeated the glutamate finding. And in the 2022 study, people in both groups said they felt about equally tired by the end of the day, the fatigue showed up in their choices and their pupils, not in what they reported. So the measurements are solid, but the interpretation that glutamate piling up is what causes mental fatigue is tentative, and the researchers say as much.

15:27Now the explanation most people have actually heard of, which is that self-control draws on a limited amount of mental energy that a first hard task uses up. This is also known as ego depletion. 23 laboratories ran a standardized version of the classic two-task experiment with 2 ,141 participants between them. When they pooled the results, they found a small effect that wasn't statistically significant, and they weren't the only ones. Another study involving 36 research groups recruited 3 ,531 people and used two different procedures. Again, the pre-specified confirmatory analyses weren't statistically significant, but when all of the data from this second study were analyzed rather than just the pre-specified analyses, There was a statistically significant depletion effect.

16:27Overall, the upshot is that the ego depletion effect hasn't been replicated well, not that ego depletion doesn't exist. The glucose hypothesis has fared even worse, despite a promising start and a run of best-seller status in airport bookshops. But what about studies showing that people perform worse on tasks requiring self-control after consuming a non-caloric sweetener instead of one containing glucose. These studies have problems too. For starters, although some of the studies investigating glucose and self-control found significant effects, other studies failed to replicate these effects. What's more, even when studies find significant effects, they are often small and have limited evidential value.

17:18So much so, in fact, that the researchers who went back and audited this literature recommend against drawing any conclusions about the link between glucose and self-control until better evidence arrives. Then the claim people repeat most that mental fatigue makes you physically weaker. The original finding is a clean one. A study done on cyclists' perseverance had 16 participants cycle on an exercise bike until exhaustion at 80 % of their peak power output, after either watching 90 minutes of documentaries or engaging in 90 minutes of cognitively challenging activities. When mentally fatigued, participants cycled for an average of 640 seconds compared to 754 when not mentally fatigued, almost two minutes less on a control duration of about 12 and a half minutes.

18:16Importantly, the cardiorespiratory and muscle energy measures were largely unaffected by which condition participants were in. In other words, there was nothing wrong with participants' legs. The one thing that did change during the ride was that cycling felt more effortful when participants were mentally fatigued. Two meta-analyses on the effect of mental fatigue on subsequent physical performance published in the same year reached different conclusions, though they also pooled rather different sets of studies. One, restricted to endurance tasks after at least half an hour of mental work, 21 studies, a little over 300 participants, concluded that although a small to medium negative effect of mental fatigue on physical performance had been reported, this effect likely reduced to non-significance once publication bias was taken into account.

19:13The other cast a wider net over randomized controlled trials, taking in short self-control tasks and strength exercise as well. 73 studies, 91 comparisons, over 2 ,500 participants, and did find a significant, if small to medium, negative effect of mental fatigue on physical performance, concluding that it was unlikely to be due to chance. Earlier reviews had suggested that although mental fatigue seems to negatively impact on endurance performances, accompanied by an increased perception of effort, it doesn't seem to impact on anaerobic and strength performances, though that larger meta-analysis found strength exercise affected too, with only all-out anaerobic efforts spared.

20:01So it turns out that neither of these explanations fares very well when scrutinized. But there is another explanation out there. Picture a small workshop with exactly one workbench. There is only ever one bench, so every job you put on it is a job that nothing else can have. The machinery of executive function can be deployed on only a limited number of things at once. Using it here carries a genuine opportunity cost, and the feeling of effort is the felt output of that calculation. It is not the bench wearing out, but the invoice for everything queuing behind it. And it gets louder as the queue gets longer.

20:45And across every one of these competing camps, one thing is agreed. Doing effortful cognitive work reliably makes people less willing to do more of it. What is fought over is why. So what actually helps? Well, sleep. 24 healthy young adults performed an effort-based decision-making task after three consecutive nights of sleep opportunity limited to three hours, and when well-rested, nine hours of sleep opportunity. Sleep restriction led participants to be less willing to invest cognitive effort in exchange for rewards, with no change in their willingness to invest physical effort. So sleep loss didn't sap their motivation or energy generally.

21:31It specifically affected their willingness to invest the effort that's of interest here. In another study, 50 undergraduates performed a maths task with varying levels of difficulty after a normal night's sleep and after sleep loss. The results showed that after sleep loss, participants selected easier problems and got more of them right. Another randomly assigned group of 58 undergraduates showed no change in percent correct answers after sleep loss because they were choosing easier problems to maintain their level of performance. Importantly, the sleep deprived students in that second study reported putting in just as much effort as the rested ones.

22:12They had lowered their ambition without feeling that they were trying any less. Sleep loss, then, doesn't seem to remove the capacity for effortful thought so much as the willingness to spend it. Breaks come next, across 19 studies involving a total of 2 ,335 participants. Taking breaks reliably decreased fatigue and increased vigor. Taking breaks did not reliably improve overall task performance, although it did improve performance on tasks that didn't require much cognitive effort. Longer breaks did more for performance than shorter ones. After especially effortful or depleting activities, 10 minutes may not be enough.

22:59When it comes to food, popular opinion outpaces the research here. Having breakfast, for example, has been found to be associated with better performance than not having breakfast in 45 studies of children and adolescents spanning almost 60 years. However, this finding was strongest among malnourished children. There were also not enough studies to draw conclusions about different types of breakfast. A separate review trying to identify the ideal breakfast was unable to reach any firm conclusions due to mixed results. Another review of children and adolescents nicely summarized the effect as being domain and time specific, with effects strongest for undernourished children and in areas including attention, executive function and memory.

23:51In adults, the picture is thinner still. A review of 38 studies found a small but robust advantage for memory from eating breakfast, and largely equivocal results for attention and executive function. When it comes to hydration, there's a debate here. On the one hand, a meta-analysis of 33 studies found that dehydration was associated with worse cognitive performance, particularly in the areas of attention, executive function, and motor coordination, and to an even greater extent when dehydration meant losing more than 2 % of body mass. On the other hand, a systematic review of 33 studies in over 3 ,500 adults specifically looking at the effect of hydration on executive function found mixed results.

24:42About half of the studies found no or unclear effects, while the other half did find effects. Which brings us back, finally, to the question I left open at the start. Pool 31, randomized, double-blind, placebo-controlled studies in rested, healthy adults and caffeine, comes out improving both reaction time and accuracy. Effects increase with dose with 200 milligrams and updoing more than smaller doses. However, while the gain in reaction time keeps growing in a straight line as the dose goes up, The gain in accuracy plateaus and then falls away at higher doses. So more caffeine does not necessarily mean better performance, just quicker.

25:27But how much of that is a gain? And how much is repair? In one double-blind study, people, some regular caffeine users, some light or non-users, came in after abstaining from caffeine overnight and did cognitive tasks before and after ingesting caffeine or a placebo. In the afternoon, those experiencing caffeine withdrawal were sleepier, felt less alert, and did worse on tests of reaction time and recognition memory. Caffeine remedied this for habitual users. For infrequent or non-users, it wasn't so clear-cut. It helped them feel less sleepy and quickened their reactions, but it didn't make them feel more alert or sharpen their memory.

26:13That benefit was cancelled out by an increase in jitteriness. Another similar study found mood, psychomotor and reinforcing effects of caffeine in caffeine users experiencing overnight withdrawal, but not in people who don't use caffeine. On the other hand, in that meta-analysis of 31 studies, the degree to which caffeine affected attention had nothing to do with how much caffeine people habitually used. So it's true that for at least some caffeine users some of the time, caffeine's effects can be explained by the relief of withdrawal symptoms. But apparently not all of the time, at least as far as attention is concerned.

26:56One thing caffeine does do though, that's beyond dispute, is block adenosine. And adenosine has to do with sleepiness. Whether it has anything to do with the rest of what I've described, the brain chemistry in frontal areas, the brain's cost keeping, the effects on decision making is an open question. So here is the idea to carry out of this. The feeling of being wiped out by a day of thinking is not weakness and it is not imagination. It shows up in the choices people make, in the size of their pupils and in the chemistry of the control regions of the brain. But it isn't the product of an empty tank.

27:38There wasn't much to empty. And remarkably, no one knows what it is. Not approximately, not modulo, a few more studies. We have a universal human experience measured in multiple ways, but no consensus as to the mechanism behind any of them. And it isn't for the lack of trying. So that's the science of mental fatigue, as we currently understand it, proceeding at the speed of science. Here's what I take away from it. Sleep deprivation doesn't sap your energy so much as your motivation to engage in cognitively demanding activities and does so in a fairly insidious way. Protect your sleep the night before anything cognitively demanding, not just your morning routine on the day.

28:25Attention wanes with time on task, whether the work is dull or demanding. So take breaks because they do help. Full breaks are better than partial breaks, and make sure they're long enough. Because if you've been doing something really demanding, 10 minutes may not be enough. Stay hydrated, but don't expect miracles. Same with don't skimp on breakfast. The effects of food on cognition are small and domain-specific and most evident in undernourished children. and the idea that willpower is basically blood glucose has flopped more comprehensively than anything else in this literature, as far as I can tell.

29:06Caffeine can help, but be honest with yourself about what it's doing. If you drink it every day, much of the lift you feel is probably relief from overnight withdrawal. If you don't, you may get less out of it than you'd expect because the jitters tend to cancel out the extra alertness. overall nothing here is going to help you get through that last soul-crushing email of the day but at least now you know that soul-crushing email isn't really all that expensive and at least the chair knows thanks again for listening to today's episode please take care out there make the most of your waking hours and get a really good night's sleep tonight see you next time and bye for now

29:54Thank you.