Falling Walls: Untangling the Mystery of Sleep

This article was published in Scientific American’s former blog network and reflects the views of the author, not necessarily those of Scientific American

Editor’s Note: The Falling Walls Conferenceis an annual, global gathering of forward thinking individuals from 80 countries organized by the Falling Walls Foundation. Each year, on November 9—the anniversary of the fall of the Berlin Wall—20 of the world’s leading scientists are invited to Berlin to present their current breakthrough research. The aim of the conference is to address two questions: Which will be the next walls to fall? And how will that change our lives? The author of this essay is speaking at this year’s Falling Walls gathering.

From our personal experience, we know that that good sleep is critical for well-being. Yet as we pay increasing attention to physical exercise and nutrition in our busy modern lives, we still often dismiss sleep as a waste of time. As Margaret Thatcher put it: "Sleep is for wimps!"

Is that really so? Sleep is common to all animals. As humans, we spend a third of our lives in slumber, vulnerable and oblivious to most external events. Our sleep is closely regulated so that if it is restricted, we ultimately compensate with longer, deeper sleep. Sleep is crucial for brain recuperation and the reorganization of synaptic connections. It is key for supporting memory and sustained attention. Poor sleep immediately affects our mood and health; impairs immunity and metabolism; and increases the risk for hypertension, diabetes and stroke. Sleep fragmentation, a common result of breathing disorders during slumber, can accelerate cancer progression. Clearly, sleep is critical for brain and body, or else, evolution would have found alternatives for us wimps.

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Although sleep has always fascinated humanity, until the 20th century it was regarded as “short death”—a notion dating back to the twin brothers Hypnos and Thanatos, Greek gods of sleep and death. Even today, we still often consider sleep as little more than idle hibernation (we switch our electronic gadgets to “sleep mode”). The systematic scientific study of sleep only began in the 1920s[KS1]  with the invention of the EEG, and deepened with the consequent identification of distinct sleep stages. Sleep stages, such as rapid eye movement (REM) sleep and non-REM (NREM) sleep, each have unique fingerprints of electrical brain activity, brain biochemistry and physiological profiles, and occur in stereotypical sequences collectively known as “sleep architecture.”

For a time, sleep research concentrated on sleep stages, as this promoted global standardization for medical treatment. But with time it became evident that such a perspective—treating brain activity as uniform—was limited and naïve, failing to capture the complexity of brain activity in supporting sleep’s vital functions. Therefore, sleep research has shifted to focus on distinct waves (oscillations) of electrical activity in specific brain regions, such as slow waves (below one hertz) and sleep spindles (10–15 hertz) occurring during NREM sleep, and how they may mediate the functional benefits of sleep.

COMPLEX LOCAL WAVES OF SLEEP AND SLEEPINESS

In the 1990s, neuroscientists moved beyond EEG markers of sleep stages to reveal activities of individual neurons that underlie slow waves. It was discovered that neurons in the cerebral cortex repeatedly switch “on” and “off” between active firing and silent periods, roughly every second. Similar slow waves were found to occur synchronously during anesthesia, so it was assumed that in sleep virtually all the billions of neurons in the cortex switch “on” and “off” together, like a giant choir singing in unison. However, some pieces didn’t fit this puzzle. For example, if a specific brain region is particularly active and involved in learning during the day, its waves during subsequent sleep are stronger and different from other brain regions. In dolphins and other marine mammals, one brain hemisphere shows slow waves while the other is continuously active as in wakefulness. Sleep disorders such as sleepwalking are associated with a complex mix of sleep and wake activity patterns occurring simultaneously, once again demonstrating that neurons do not always switch on and off together during NREM sleep.

With these observations in mind, we decided to employ a novel approach to investigate how uniform brain activity actually is during the slow waves of NREM sleep. Occasionally, it is necessary to implant electrodes in multiple brain regions to aid diagnosis and pinpoint the seizure onset zone in epilepsy patients not responding to medical treatment. Together with sleep investigators Chiara Cirelli and Giulio Tononi and neurosurgeon Itzhak Fried, we studied the activity of individual neurons across many brain regions in these patients during sleep. We found, in contrast to the wide-held dogma of the time, that the slow waves of NREM sleep typically occur locally (out of phase), where different brain regions are simultaneously active and silent. We verified that this was a general principle of normal sleep, present in other mammals and unrelated to epilepsy. Put simply, local sleep waves are the rule rather than the exception.

Based on these findings, we further hypothesized that local slow waves, which typically go unnoticed with scalp EEG, may nevertheless be present in brain activity during the entire spectrum leading from awake sleepiness to full-fledged sleep. While fatigue can lead to momentary global sleep attacks (known as “micro-sleep” episodes) we suspected that local sleep waves may also occur when our eyes are open and we are engaged with the world.

We demonstrated that in awake sleep-deprived rats and humans, local sleep waves occur in parallel to cognitive lapses, and specifically in brain circuits engaged in the task at hand. Finally, not only are there “islands of sleep” during wakefulness, but sleep may also contain “islands” of wake-like activity. We also found that the activity of individual neurons during human REM-sleep dreaming is linked to eye movements and the switching of mental images.

With this emerging yin and yang picture that includes “islands of sleep” and “islands of wakefulness,” sleep remains a continent that is still largely terra incognita. Today, the conceptual walls dividing sleep and wakefulness are tumbling, giving way to a new framework whereby sleepiness represents a complex mixture of sleep and wakefulness occurring simultaneously across different brain circuits.

At a practical level, sleepiness is a major cause of accidents with effects comparable to alcohol consumption. Unfortunately, we do not yet have reliable and efficient methods to measure how tired an individual is at any given time. It would therefore be valuable to develop methods to detect and count “islands of sleep” and identify when their occurrence has reached a dangerous threshold to alert and prevent individuals from engaging in professional activities where vigilance is key such as driving, aviation and surgery.

A BRIGHT FUTURE FOR SLEEP RESEARCH

Beyond progress in basic sleep research, several ongoing investigations have important applicable potentials:

—Understanding and measuring sleep depth. To what extent are we “disconnected” from the external environment at any given time, and what mediates such disconnection? While some people can sleep through just about anything (as toddlers often do), others are easily aroused (e.g. during stress, or in the elderly). Once we better understand the brain activities that determine awakenings, we could develop neurobiologically inspired monitors of sleep depth. With time, such devices, possibly integrated into “smart” bedrooms, could measure sleep quality, as thermometers measure body temperature. Similar monitors may be used during surgeries to eliminate intraoperative awareness and minimize the risks of overly deep anesthesia. More broadly, “sleep depth” monitors could aid medical and ethical decisions in vegetative patients and severe dementias, where we remain uncertain about the degree to which a person is experiencing the outside world.

—Sleep as a unique window to aid medical diagnosis. Specific alterations in sleep activities are present in every neuropsychiatric brain disorder, and sleep monitoring offers rich data with minimal inconvenience. By moving beyond the simple concept of sleep stages to define more precisely how normal distinct sleep waves are in any individual, we should be able to improve early detection of a wide range of brain disorders including Alzheimer’s, Parkinson’s and autism, or assess the prospects of recovery from stroke.

—Improving sleep: beyond pills. Medications to induce sleep are associated with multiple drawbacks such as tolerance and grogginess upon awakening. Ongoing studies are investigating the extent to which non-invasive interventions (such as precisely-timed auditory and electrical stimulation) can be used to boost sleep waves and aid cognition and memory. Sleep gadgets may become part of our lives, bringing relief to insomniacs and helping fight memory decline.

In conclusion, better understanding of sleep physiology should ultimately have profound effects on our future lives, promising a bright future for sleep research.

The Falling Walls Conference is supported by the German Federal Ministry of Education and Research, the Helmholtz Association, the Robert Bosch Stiftung and the Berlin Senate. It receives support and advice from a wide variety of international top-class universities and research institutions as well as foundations, corporations, noted individuals and non-governmental organizations.

Bio

Yuval Nir is an assistant professor at Tel Aviv University, Israel.

MORE TO EXPLORE

Selective Neuronal Lapses Precede Human Cognitive Lapses Following Sleep Deprivation. Yuval Nir, Thomas Andrillon, Amit Marmelshtein, Nanthia Suthana, Chiara Cirelli, Giulio Tononi, and Itzhak Fried in Nature Medicine, in press.

Single-neuron Activity and Eye Movements During Human REM Sleep and Awake Vision. Thomas Andrillon, Yuval Nir, Chiara Cirelli, Giulio Tononi, and Itzhak Fried in Nature Communications, Vol. 6, page 7,884 ; August 11, 2015.

Regional Slow Waves and Spindles in Human Sleep. Yuval Nir, Richard J Staba, Thomas Andrillon, Vladyslav V. Vyazovskiy, Chiara Cirelli and Giulio Tononi in Neuron, Vol. 70, pages 153–169; April 13, 2011.

Local Sleep in Awake Rats. Vladyslav V. Vyazovskiy, Umberto Olcese, Erin C. Hanlon, Yuval Nir, Chiara Cirelli and Giulio Tononi in Nature, Vol. 472, pages 443–447; April 28, 2011.