May 9th, 2023
Written by: Sophie Liebergall
This past year, astrophysicists used NASA’s James Webb Space telescope to observe a star that is over 33 billion light years away from earth. Back on earth, particle physicists used the Large Hadron Collider in Switzerland to confirm the existence of incomprehensibly tiny subatomic particles. But despite these astounding scientific and technologic advances, we still have a lot to learn about what is going on in the organ inside our own skulls! In part one of what will be a two-part series, we discuss a few of the fundamental questions about the brain that have remained mysterious to neuroscientists.
1. Where do our memories go when we put them in long-term storage?
For a brain to perform complex tasks, such as telling the body to execute a series of movements or being able to recognize and evade a predator, it must be able to recall information that was gathered during previous experiences. Neuroscience researchers divide memory storage into two stages: short-term memory and long-term memory.1 When the brain senses something in its environment, it can hold that information for a few seconds to minutes as a short-term memory.2 Over time, scientists have gathered clues that short-term memories (at least those of conscious facts and events) are stored in the hippocampus, an almond-size region nestled on either side below the brain’s surface on either side.3 But sometimes the brain needs to hold onto information for longer periods of time (up to a lifetime) so that is can be recalled later. We’re fairly certain that long-term memories aren’t stored in the hippocampus; but where exactly these long-term memories go remains a mystery. Several recent studies seem to suggest that, unlike short-term memories, long-term memories may be widely distributed in the cerebral cortex (the large surface of the brain that is used for complex thought), with different features of the memory spread across different regions.4,5 You can read more about the process of memory formation and how it can go wrong in some diseases here!
2. Why do we need to sleep?
Evolution has shaped the human body into an elegant and efficient machine, with a versatile digestive system, a continuously beating heart, and a thinking brain. However, one of our basic biologic functions, sleep, seems like something that should have been stamped out by evolution many generations ago. When we sleep, we are essentially unconscious for up to one-third of the day. For our ancestors, this is a time when they were particularly vulnerable to predators and unable to gather food. So why, then, has sleep survived the test of natural selection?
Sleep is absolutely necessary for all animals (from armadillos, who sleep up to twenty hours each day, to giraffes who need just two hours of sleep a day).6 After just a couple days of total sleep deprivation, many people will start to show symptoms of psychosis.7 And if the sleep deprivation continues, it can even be deadly. In a study from the 1980s, which would likely be forbidden under contemporary ethical standards, researchers subjected a group of rats to total sleep deprivation. All of the rats died by the 32nd day of the study.8 The ultrarare genetic disease Fatal familial insomnia gives further insight into the danger of insomnia in humans. Patients with Fatal familial insomnia slowly lose their ability to fall and stay asleep.9 Tragically, these patients always die soon after they completely lose their ability to sleep.
Sleep is important for a variety of our body and brain’s normal functions: solidifying events that occurred during the day as long term memories,10 recalibrating the strength of the connections between brain cells,11,12 balancing the hormones that control our appetites and metabolism,13 and clearing the toxic byproducts of brain cell activity.14 But scientists still do not know what function (or functions) of sleep are the primary reason why it is essential for survival. Read more about the possible hypothesis for why we sleep in this PNK article!
3. Why do we dream?
Even more mysterious than the question of why we sleep is the question of why we dream. Though sleep has been a target of neuroscience research for decades, there are inherent challenges to studying dreaming that prevent us from using some of the traditional tools of neuroscience research. The study of dreams still largely relies on dream reports, when a person wakes up and verbally reports or writes down whether they were dreaming and what their dream was about. Dream reports are often unreliable because of the bias and imperfect memory of the dreamer. This can prevent researchers from making objective scientific conclusions from dream reports. Furthermore, all animals clearly display some form of sleep, but there is no conclusive evidence that other animals have dreams. This makes it challenging or even impossible to study dreaming using laboratory animals, which generally allow us to perform important experiments that would take too long or be too dangerous in humans.
Though we have recently developed more sophisticated tools that allow us to correlate the dream reports of humans with measures of brain activity, many of these studies have only raised more questions. It was once thought that dreaming only occurred during rapid eye movement (REM) sleep, the phase of sleep during which brain waves look most similar to the waking state. But more recent evidence suggests that dreams occur during both REM and non-REM sleep (though dreams that occur during REM sleep do seem to be more vivid than the dreams that occur during non-REM sleep).15,16
Another strange aspect of dreaming is called the dream-lag effect, which describes a phenomenon in which you’re most likely to dream about real life events that happened 5-7 days ago.17 And we still don’t have a clue as to why some people are prone to sleepwalking: a state in which individuals are clearly deep in a dream, but somehow are aware of their surroundings enough to navigate a space, consume food, or even drive a motor vehicle.18 You can learn more about the neuroscience of dreaming here!
4. How do the general anesthesia drugs used during surgery make you unconscious?
General anesthetics, the class of drugs which cause temporary unconsciousness, have made it possible for doctors to perform lifesaving and life-altering surgeries that would otherwise be impossibly painful for patients. General anesthetics are some of the most safe and reliable medications that are administered by doctors. But we still don’t have an understanding of where general anesthetics act in the brain, or of what their ultimate effects are on brain processes. Even though anesthetic drugs all have the same end effect of making a patient unconscious, anesthetics can come in all different shapes and sizes. Some, like xenon gas, have a structure as simple a single atom, whereas others, like alfaxalone, have a complex structure with many branches and rings.19,20 Some are inhaled as a gas, whereas others are injected into the bloodstream. And, strangely, general anesthetics don’t just sedate animals with complex brains like humans. They also impair the movement and environmental responsiveness of plants and even single-celled organisms!21 You can learn more about the possible mechanisms of general anesthetics and their relationship with sleep in this PNK article.
5. How does each area of the brain know what function it is supposed to perform?
In the mid-19th century, in the early days of modern neuroscience, the French physician Paul Broca learned of a patient with a unique neurologic condition. This patient had lost the ability to generate speech, but had somehow maintained the ability to comprehend speech.22 When this patient died, Broca performed an autopsy, where he discovered that the patient had sustained an injury to a very specific area of their frontal lobe. Broca’s work inspired other physicians of his age to look for injuries to specific areas of their brains in their patients with specific neurologic symptoms. If multiple patients with the same symptoms had an injury in the same region, then it could be assumed that an injury to that region was the cause of the symptom. These studies of localized brain injuries led neurologists to believe that different regions of the brain are responsible for the different functions of the brain. For example, one region of the brain is required for the ability to move a hand, whereas another region of the brain is required to read language.
Modern-day neuroscientists and neurologists take the idea that certain regions of the brain are responsible for certain functions for granted. But there is a great deal of complexity to this picture that we have yet to understand. The exact mapping of the functions of the brain can vary between individuals – sometimes in dramatic ways. For example, most people have the speech control area of their brain somewhere on the left side of their brain. But occasionally, in people who are left-handed, the speech control area is instead found on the right side.23 This variability between individuals suggests that the process of assigning a function to a specific brain region doesn’t follow a simple blueprint. But we still don’t know how the brain knows which functions it needs to perform. And we also don’t know each function is assigned to a particular region of the brain.
Stay tuned for part two with five more big unanswered questions in neuroscience coming this summer!
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Cover photo made with biorender.com.
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