A study in mice by a Harvard Medical School (HMS)-led research team has reported new insights into what is happening in the brain while we daydream. The study, through which the researchers tracked the activity of neurons in the mouse visual cortex, provides tantalizing, although preliminary, evidence that daydreams can shape the brain’s future response to what it sees. And while a causal relationship needs to be confirmed in further research, the team says its results offer an intriguing clue that daydreams during quiet waking may play a role in brain plasticity—the brain’s ability to remodel itself in response to new experiences.

The scientists also suggested that their observations and results align with a growing body of evidence in rodents and humans that entering a state of quiet wakefulness after an experience can improve learning and memory.

The team, headed by Mark Andermann, PhD, professor of medicine at Beth Israel Deaconess Medical Center, and professor of neurobiology at HMS, reported on their results in Nature, in a paper titled, “Cortical reactivations predict future sensory responses.”

You are sitting quietly, and suddenly your brain tunes out the world and wanders to something else entirely—perhaps a recent experience, or an old memory. You just had a daydream. Yet despite the ubiquity of this experience, what is happening in the brain while daydreaming is a question that has largely eluded neuroscientists.

Scientists have spent considerable time studying how neurons replay past events to form memories. “Many theories of offline memory consolidation posit that the pattern of neurons activated during a salient sensory experience will be faithfully reactivated, thereby stabilizing the pattern,” the team noted. “Reactivations, by definition, are patterns of activity that are similar to those that occurred during recent experiences.” Most study has focused on the activity of neurons in the hippocampus, a seahorse-shaped brain region that plays a key role in memory and spatial navigation. By contrast, there has been little research on the replay of neurons in other brain regions, including the visual cortex. Such efforts would provide valuable insights into how visual memories are formed. As the authors further noted, “First observed and most commonly studied in the hippocampus, reactivations have also been observed in the amygdala, prefrontal cortex, visual cortex, and elsewhere.”

“My lab became interested in whether we could record from enough neurons in the visual cortex to understand what exactly the mouse is remembering—and then connect that information to brain plasticity,” said Andermann. For their reported study, the team tracked the activity of neurons in the visual cortex of the brains of mice while the animals remained in a quiet waking state. The team repeatedly showed mice one of two images, each consisting of a different checkerboard pattern of gray and dappled black and white squares. Between images, the mice spent a minute looking at a gray screen. The team simultaneously recorded activity from around 7,000 neurons in the visual cortex.

“… we recorded and tracked the activity of approximately 6,900 neurons simultaneously in the lateral visual cortex across days while mice passively viewed well-controlled presentations of identical stimuli, separated by minute-long interstimulus intervals during which reactivations should occur,” they explained.

The researchers found that when a mouse looked at an image, the neurons fired in a specific pattern, and the patterns were different enough to discern image one from image two. More importantly, when a mouse looked at the gray screen between images, the neurons sometimes fired in a pattern that was similar, but not identical, to that when the mouse looked at the image. This was a sign that the animal was daydreaming about the image. These daydreams occurred only when mice were relaxed, characterized by calm behavior and small pupils.

Moreover, the patterns of activity during a mouse’s first few daydreams of the day predicted how the brain’s response to the image would change over time. “We wanted to know how this daydreaming process occurred on a neurobiological level, and whether these moments of quiet reflection could be important for learning and memory,” said first author Nghia Nguyen, a PhD student at the Blavatnik Institute at HMS.

Unsurprisingly, mice daydreamed more about the most recent image, and the findings suggested that they had more daydreams at the beginning of the day than at the end, when they had already seen each image dozens of times. But the researchers also made a completely unexpected discovery. Throughout the day, and across days, the activity patterns seen when the mice looked at the images changed—what neuroscientists call “representational drift.” Yet this drift wasn’t random.

Over time, the patterns associated with the images became even more different from each other, until each involved an almost entirely separate set of neurons. Notably, the pattern seen during a mouse’s first few daydreams about an image predicted what the pattern would become when the mouse looked at the image later. “There’s drift in how the brain responds to the same image over time, and these early daydreams can predict where the drift is going,” Andermann said. The team further noted, “ … we could accurately predict future changes in stimulus responses and the separation of responses to distinct stimuli using only the rate and content of reactivations. Thus, reactivations may contribute to a gradual drift and separation in sensory cortical response patterns, thereby enhancing sensory discrimination.”

Finally, the researchers found that the visual cortex daydreams occurred at the same time as replay activity occurred in the hippocampus, suggesting that the two brain regions were communicating during these daydreams. “During the minute after a visual stimulus, we observed transient, stimulus-specific reactivations, often coupled with hippocampal sharp-wave ripples,” they wrote. Based on the results of the study, the researchers suspect that these daydreams may be actively involved in brain plasticity.

“When you see two different images many times, it becomes important to discriminate between them. Our findings suggest that daydreaming may guide this process by steering the neural patterns associated with the two images away from each other,” Nguyen said. “Thus, reactivations may contribute to a gradual drift and separation in sensory cortical response patterns, thereby enhancing sensory discrimination,” the authors added. While acknowledging that this relationship needs to be confirmed through future work, Nguyen added that learning to differentiate between the images should help the mouse respond to each image with more specificity in the future.

Next, the researchers plan to use their imaging tools to visualize the connections between individual neurons in the visual cortex and to examine how these connections change when the brain “sees” an image. “We were chasing this 99% of unexplored brain activity and discovered that there’s so much richness in the visual cortex that nobody knew anything about,” Andermann commented.

Whether daydreams in people involve similar activity patterns in the visual cortex is an open question, and the answer will require additional experiments. However, there is preliminary evidence that an analogous process occurs in humans when they recall visual imagery. Prior research has shown that brain activity in the visual cortex increases when people are asked to recall an image in detail, while other studies have recorded flurries of electrical activity in the visual cortex and the hippocampus during such recall.

For Andermann and colleagues, the results of their newly reported study and of other research hint that it may be important to make space for moments of quiet waking that lead to daydreams. For a mouse, this may mean taking a pause from looking at a series of images and, for a human, this could mean taking a break from scrolling on a smartphone.

“We feel pretty confident that if you never give yourself any awake downtime, you’re not going to have as many of these daydream events, which may be important for brain plasticity,” Andermann concluded.

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