Caffeine’s little memory jolt garners a lot of excitement

There are some scientific topics that are bound to generate excitement. A launch to the moon, a potential cure for cancer or any study involving chocolate will always make the news. And then of course there’s caffeine. More than half of Americans have a daily coffee habit, not to mention the boost offered by tea, soda, chocolate and energy drinks. We’d all love to believe that it has more benefit than just papering over a poor night’s sleep.

This week, scientists reported that caffeine could give a jolt to memory consolidation, the step right after your brain acquires a memory. During memory consolidation, activity patterns laid down in your brain become more permanent. The study suggested that caffeine might perk up this stage of memory formation. But while it’s an interesting finding, the scientific brew may not be strong enough to justify your coffee habit.

Caffeine is a great way to wake you up. It blocks the action of adenosine, a chemical messenger that promotes sleep. Caffeine also has indirect effects on other chemical messengers such as norepinephrine, the neurotransmitter that gives us our famous “fight or flight” response. The net result is increased attention, wakefulness and faster responses.

But attention, focus and response time are not memory. And previous studies of memory, says neuroscientist Michael Yassa, the lead author on the new study, were “all over the place.” So Yassa, then at Johns Hopkins University (he’s now at the University of California, Irvine), and undergraduate student Daniel Borota decided to study the effects of caffeine on memory “in a rigorous way.”

There are several ways to study how caffeine could affect memory. For example, scientists can give study participants a dose of caffeine and give them a list of objects to memorize. A day later, the participants get a new list and are asked to remember which words on it they have seen before. This is a basic test for recall that’s commonly used to study learning and memory. And in those sorts of tests, caffeine doesn’t seem to do much.

Borota, Yassa and their group wanted to dig in deeper. They were interested in memory consolidation. After someone acquires a memory, molecular processes take place in your brain to make the neural patterns of that memory more permanent.

And the scientists wanted to get a more detailed look at memory by looking at pattern separation, the ability to differentiate one remembered item from other similar items that you haven’t seen before. This ability isn’t likely to come out on most basic recall tests, which are too simple to make the brain rely on pattern separation. Remembering if you’ve seen an apple or a chair is one thing. Remembering if you’ve seen a green apple or a red apple requires more discrimination. It requires pattern separation.

The scientists adapted a well-known test for memory consolidation in animals. “We picked something that has been done for many years in rodent studies, to administer the drug after the study episode has taken place,” Yassa says. Then, if the animals show an increase in memory performance after getting caffeine, “the only explanation is that it has strengthened the memories once they’d been laid down.”

In the new study, the lab rats were college students who did not normally consume caffeine. The researchers showed the participants a series of images. An empty jar, a flower, a saxophone. Immediately after the images, the subjects got either a placebo pill or a pill with 200 milligrams of caffeine, the equivalent of a tall Starbucks Pike Place. After saliva swabs to examine how quickly the students metabolized the caffeine, the participants went home with orders to get a good night’s sleep. The next day, the students came back to the lab and were presented with another image series. A jar with jam in it, a flower, a rubber duck.  They were asked to rate items as “old” (saw it yesterday), “new” (entirely new), or “similar” (it’s a jar, but it’s a jar with jam in it).

In a paper published January 12 in Nature Neuroscience, the group reported that caffeine made a difference — not between old and new, but between old, and “similar.” It’s still a flower, but now it’s pink instead of purple. Because they received the caffeine after they had been exposed to the first series of pictures, the scientists can conclude that the increase in performance must have been due to increases in memory consolidation, not in memory formation. Further experiments showed that there was a dose-response effect: 100 milligrams of caffeine had no effect, while 200 milligrams worked. But at 300 milligrams, you begin to have too much of a good thing, and students began to complain of side effects.

“I do think it’s a very clever design, using an ingenious task,” says Jon Simons, a cognitive neuroscientist at the University of Cambridge in England. “It provides the first real insights into the effects of caffeine on consolidation.” It also points to a role for the hippocampus, an area in the brain that plays an important role in learning and memory. The CA2 region of the hippocampus, Yassa notes, has a large concentration of adenosine receptors, much higher than the surrounding areas. Because caffeine blocks adenosine receptors, this might be how the drug is having its effect on pattern separation and memory consolidation. Some studies in rodents have hinted at this mechanism, but further experiments are needed to show that caffeine, acting in the CA2 region specifically, increases pattern separation. 

Although the study shows a new role for caffeine in memory consolidation, it may not be the whole bean on caffeine. The effect on consolidation memory is extremely small, says Yassa, “only about a 10 percent gain in some places.” And because of the small number of participants in the study, the data just passed, but didn’t soar beyond, statistical muster. “I wish they had tested a few more participants and reported a few more statistical tests,” says Simons, “so that the fascinating findings the authors think they have observed would be demonstrated more convincingly.”

George Kemenes, a neuroscientist University of Sussex in England, also has some concerns about the statistics. “I found the whole experimental design very elegant and satisfying the highest professional standards,” he says. “The problem with the weakness of the statistics may indeed have arisen because of the relatively low number of experimental subjects.”

In particular, Kemenes is concerned that one of the figures uses a statistical test, the one-tailed Student’s t-test, requires you to assume that the result will only turn out one way: “that caffeine can only cause the choice of ‘similar’ category to increase and the choice of ‘old’ category to decrease,” Kemenes says. It might be better to do a two-tailed Student’s t-test, which does not assume that a result will turn out one way or the other. But with an effect this small, Kemenes points out, “a two-tailed test might not have detected significance.” Simons agrees, and while he appreciates the findings, he’d like to “see a replication of these effects with larger sample sizes, because some of the results are a little weak, only just hovering around conventional thresholds for statistical significance.”

But Yassa is confident that the one-tailed t-test is the correct analysis. “We had a directional hypothesis to test,” he says. “For the critical analyses on which we based our conclusions [an analysis that compares how participants discriminate the ‘similar’ objects from ‘old’ objects] we moved to two-tailed tests so that we can remove any potential bias.”

The study also used participants who generally don’t drink caffeine. Yassa says that the average caffeine intake among the participants was cut off at 500 milligrams per week, about two grande Americanos, and most participants drank much less. The participants weren’t told whether they were getting caffeine or placebo in their pills, and when asked, most could not tell what they had been given. High-dose coffee drinkers like Yassa (and yours truly) may not see any memory benefit. But then again, we might. “It shouldn’t be taken as a rule of thumb that more is better,” Yassa says. “For everyone it’s going to be different.” And while memory consolidation and pattern separation are important aspects of memory, they are not all there is to remembering.

So while you might think that drinking a coffee after class will perk up your chances on the next day’s exam, the effect in this paper probably isn’t large enough to depend on. By all means have your latte, but throw in a little studying on top. 

Editor’s note: This story was updated at 1:00 p.m. January 17, 2014, to correct a reference to degrees of similarity when distinguishing between similar and old objects. While there was an overall effect of caffeine, there was no significant interaction.