Guest Post by Sadie (Sarah) Witkowski, Northwestern University

As one of five children, my mom has plenty of stories about her and her siblings’ misadventures. One of my favorites revolves around my “weird” Uncle Dorsey and his early scientific endeavors. When my mom was about 8 years old, her older brother slipped a tape player under her bed every night to quietly play a reading of “The Raven” by Edgar Allen Poe. Night after night he would play the tape, trying to test whether my mom would spontaneously recite the poem from all her exposure. The way she tells it, my mom woke up every time the recording started to play. Sure, she can still recite the first few lines, but only because she was awakened by the poem night after night.

My uncle never managed to get my mom to “sleep learn” (aka hypnopedia) but it turns out some of his ideas might not have been so misguided. While sleep learning has been debunked, cognitive neuroscientists in the Paller Lab at Northwestern University where I work, and others are now discovering ways to use stimuli like sound or odor cues during sleep to strengthen memories.

Early researchers made the same mistake as Uncle Dorsey and thought we could learn new material during sleep, ala Brave New World. As in Aldous Huxley’s dystopian novel, experiments attempting this sleep learning were often based on the false premise that sleep is just like a hypnotic state. In the 1920s, some researchers believed they could teach people totally new information by playing audio recordings to a sleeping participant. Inventors got in on the racket, selling devices that promised to teach you as you slept. It wasn’t much different from the episode of Dexter’s Lab when he tries to use a massive gadget to teach himself French as he sleeps. But unlike in the cheesy cartoon, these devices didn’t work during sleep.

Not until the 1950s did researchers discover the touted effects of hypnopedia were actually not due to sleep at all. Instead these contraptions were actually awakening people. The debunkers could tell by using a relatively established technique called electroencephalography (EEG), recording the brain’s electrical signals through electrodes placed on the scalp. Using EEG on sleep learning participants, researchers could tell that participants were actually awake (something we still do in research today). This revelation all but ended research regarding using sleep as a cognitive tool. Fifty years later, we neuroscientists now know it is possible to alter memory during sleep, just in a different way than previously expected.

In a 2007 paper, neuroscientists at Lübeck University reported that smells, which were associated with previously learned material, could be used to cue the sleeping brain. The study authors had taught participants the locations of objects on a grid, just like the game concentration, and exposed them to the odor of roses as they did so. Next, participants slept in the lab and the experimenters waited until the deepest stage of sleep, slow-wave sleep, to once again expose them to the odor. When they awoke, the participants were significantly better at remembering where the objects were located. This only worked if they had been exposed to the rose smell at learning and then smelled the odor during slow-wave sleep. If they were only given the odor during sleep or during REM sleep, the cue did not work.

It almost seemed too good to be true. Could scientists really “tag” memories during learning with a smell and then persuade the participant’s brain to rehearse it during sleep? Multiple studies since the initial paper verified the finding, and there were even new variations such as using sound cues instead of odors.

The Paller Lab has since published multiple papers demonstrating that neuroscientists can link a single sound to a single object and reactivate it individually. For example, as a study participant, you could play concentration and learn the cat is in the lower left corner and the teakettle is in the upper right. When you learned the cat, you heard a meow, and when you learned the kettle, you heard a whistle. Now if we were to play only one of those sounds during slow-wave sleep such as the meow, you would actually remember the cat’s location even better than the kettle. Keep in mind, both of these items were initially learned equally well, showing the sleep-cueing preferentially helped the cat. This ability to select specific memories to reactivate is called targeted memory reactivation (TMR).

We call it TMR because we believe playing a sound cue like this reactivates the memory of learning the object’s location from the previous task. Those at my lab believe this replay of the memory allows the brain to strengthen its memory representation, thus leading to better recall. Working with rats, Daniel Bendor and Matthew Wilson of MIT found exactly this expected replay when they administered sound cues related to previous learning.

Neuroscientists are now starting to put this TMR to work. One recent study from my group operated a lot like Guitar Hero. James Antony, now a postdoc at Princeton University, but a graduate student at the time, had participants learn two musical sequences on a keyboard. The “songs” were composed of four “notes,” which appeared as falling circles on the screen, much like the actual video game. After learning both songs equally well, participants took a nap during which Antony cued them with one of the songs. When they were retested after sleep, participants were better at the sleep-cued song than the uncued one. Think of how quickly you could learn a new musical instrument or song, just by reminding your sleeping brain of previous learning!

We’re still on the frontier of understanding the sleeping brain. For an activity that we do for about one-third of our life, there are more questions than answers.

Although some translational research has started to surface, we still don’t know the boundaries of TMR or sleep cueing in general. In a 2017 paper, postdoctoral researcher Laura Batterink, also in the Paller Lab, found that TMR cueing in combination with REM sleep led to better recall of vocabulary words that were cued during an afternoon nap. This research seems to point to REM sleep as a beneficial state when cued memories are integrated into preexisting memory networks.

Outstanding questions that we have yet to address include: Does this work for foreign language (i.e., grammar learning) learning, or just learning foreign vocabulary words? Could it be used to help maintain memory performance in an aging population? Does reactivating some memories mean that others are wiped away even more quickly?

I’m personally interested in how these reactivated memories might be changing due to these cues. My current projects are aimed at investigating whether cueing causes the whole memory to maintain detail or whether these cues might be consolidating the ‘gist’ of the memory, thereby losing extraneous detail. Alternatively, TMR may help boost all aspects of memory consolidation and show cognitive costs only for uncued items.

We have some hunches, and new projects to address these questions are cropping up all the time. But we’re still on the frontier of understanding the sleeping brain. For an activity that we do for about one-third of our life, there are more questions than answers. Maybe weird Uncle Dorsey and his Poe tapes actually were prescient of the future for sleep research.

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Sadie Witkowski grew up in the small town of Dripping Springs, Texas, before attending University of Texas at Austin for her dual degrees in Psychology and Plan II Honors. From there, she moved to Chicago and is currently working on her Ph.D. in psychology at Northwestern University, focusing on sleep and memory. In her spare time, Witkowski interviews graduate students about their research for her podcast, PhDrinking.

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