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Secrets Of Sleep

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Harvard Medical School investigators at Massachusetts General Hospital have developed a system to accurately track the dynamic process of falling asleep, something not possible with existing techniques.

Combining key physiologic measurements with a behavioral task that does not interfere with sleep onset gives a better picture of the gradual process of falling asleep, the researchers reported in PLOS Computational Biology. In addition to being a powerful tool for future research, the system could provide valuable insights into diagnosing and understanding sleep disorders. 

“While our personal experience tells us that falling asleep is a gradual process, current clinical methods define only a single point in time at which one has fallen asleep,” said Michael Prerau, HMS instructor in anaesthesia at Mass General and lead author of the paper. “Our new research shows that it’s not simply when you fall asleep that’s important, it’s how you fall asleep that really matters. We now have the power to chart the entire trajectory of your neurological, physiological and behavioral activity as you transition from awake to asleep, rather than simply reporting the time it takes.”

In their paper, the investigators describe developing a method that continuously estimates the degree to which an individual is awake at each point during the sleep onset process. “This is a real paradigm shift in the way we study sleep onset,” said Patrick Purdon, HMS assistant professor of anaesthesia at Mass General and senior author of the study. “By quantifying the dynamic changes in brain activity and behavior during the transition from wakefulness to sleep, we now have a rigorous framework with which to study disorders of sleep onset, such as insomnia or narcolepsy.”

To link changes in brain activity to loss of consciousness during sleep onset, the investigators developed a new, minimally disruptive means of tracking behavior as someone falls asleep. One earlier method asks participants to respond to auditory cues, something that could disrupt falling asleep. Actigraphy, another method used in most clinical sleep devices and consumer wearables, measures movement, which cannot distinguish between sleep and motionless wakefulness.

To get around these problems, the investigators developed a new behavioral task that is accurate without disturbing sleep.

Credit Michael Prerau, MGH
Sleep study participants are asked to squeeze a small ball with their hand in time with their breathing as they fall asleep, allowing investigators to track the dynamic changes in brain and body during sleep onset.

Instead of responding to a sound, a participant holds a small rubber “stress ball” in one hand and is asked to squeeze the ball with every intake of breath and release it when exhaling. A special glove on that hand and electrodes on the forearm measure both the timing and the force of each squeeze.

In this way, the participant’s own breathing acts as the stimulus, and the squeezes act as the behavioral response. Gradually, more and more squeezes are mistimed with the person’s breathing, or totally missing. Measuring the force exerted by the forearm muscle also reflects how the strength of the squeeze drops with sleep onset.

At the same time as the ball-squeeze measurements are taken, EEG readings track three brain wave patterns previously associated with falling asleep: decreasing power in the alpha frequency range and increasing power in delta and theta frequencies. The combination of all of these measures—the timing and strength of ball squeezes and the change in brain wave levels—is used to calculate what the investigators call wake probability, an estimate of how awake a participant is during sleep onset.

Testing their model in healthy volunteers over several nights provided more-accurate results than traditional methods of sleep determination did. It also revealed differences in how sleep onset occurs in different individuals.

Current clinical criteria define sleep as beginning when the power of an individual’s alpha-range brainwaves disappears. While seven of the nine study participants followed this pattern, two participants continued to correctly time their ball squeezes for several minutes after alpha levels had dropped. Only when the power in their brainwaves at the theta and delta frequencies had risen did both the behavioral and physiological measures indicate that they were asleep.

“These participants continued to respond to the task, even though current clinical measures would say they were still asleep, which was clearly not the case,” said Prerau. “These results suggest that it is the presence of delta and theta power, rather than the lack of alpha power, that is necessary for the cessation of behavior. We may need to carefully re-examine the way sleep onset is defined, since behavior is an essential component of the story that is not measured clinically.”

By characterizing the trajectory of the sleep onset process in healthy individuals, Prerau and Purdon believe this study will ultimately shed light on what happens in patients who have trouble falling asleep, leading to an improved ability to understand and diagnose sleep disorders as well as to more precisely measure the effect of sleep medications. This method could also be used to track drowsiness in situations in which alertness is vital.

The study was supported by National Institutes of Health New Innovator Award DP2-OD006454.

Adapted from a Mass General news release.

This story was originally published by Harvard Medical School on Nov. 21, 2014.