Book Offers Insight On Importance Of Sleep For Memory

If you want to optimize your memory and intelligence, grab some Z's. That's the message behind the new book "REM Illumination Memory Consolidation".
Written by Dr. Timothy J. Walter, a sleep medicine physician and neurologist, "REM Illumination Memory Consolidation" integrates different research findings on sleep and memory into the first-ever cohesive theory about the overall process. Dr. Walter has translated the complex neurobiology concepts into plain English so that any reader can understand and benefit from this information.
"REM Illumination" sheds light on at least one of the reasons why we dream: for the storage of new memories and their incorporation into the matrix of all our existing memories.
In the book, Dr. Walter describes how a sleeper's brain progressively cycles through sleep as it "uploads" and consolidates recent memories. While in REM sleep, dreaming is most vivid and the times of high dream action and emotion may be the conscious representation of this memory linking process.
The REM sleep in the first 90-minute sleep cycle is quite short. However, as we cycle through different stages of sleep, each REM sleep period gradually increases in length until the last cycle, where REM sleep may be more than an hour in duration.
"This means that seven to eight hours of high-quality sleep are probably required for optimal mental functioning," explained Walter. "Most of your REM sleep occurs during the last 90-minute cycle, so if you sleep for only five to six hours, you're cheating yourself out of the longest period of REM sleep. Sleep is like paying your mortgage. You pay only interest up front and don't get to the principle until the end. REM sleep is the principle."

Deep Sleep Plays Role In Visual Learning

A relationship has been observed between deep sleep and the ability of the brain to learn specific tasks. Researchers at Brigham and Women’s Hospital (BWH) have now shown that the processes that regulate deep sleep may affect visual learning.
“These findings show that deep sleep is important for visual learning and possibly the ability of the brain to learn new tasks,” said Daniel Aeschbach, researcher in the Division of Sleep Medicine at BWH and lead author of the study.
Deep sleep, also called slow wave sleep, is a period of non-rapid-eye-movement sleep when very large brain waves, called slow waves, can be observed in the EEG, which is a recording of the brain waves. Slow waves are thought to reflect the need for sleep, but their exact function is unknown. Researchers sought to determine the function of these waves in visual learning.
Aeschbach and colleagues trained healthy subjects on a visual learning task in which they were required to determine on a computer screen the orientation of a few dashes that were embedded in a field of horizontal dashes. Subjects were tested on their accuracy of performing this task before and after they had slept for a period of four hours. One group of subjects slept normally, with no interruptions, and their visual skill in performing the task improved after sleep. In another group, researchers suppressed the occurrence of slow waves by playing targeted acoustic tones while subjects were asleep. The tones did not wake the subjects, but prevented them from slipping into deep sleep as monitored on the EEG. This group was also tested in the visual task after sleep and their skill did not improve.
Researchers suggest that these findings could have clinical implications for conditions like depression and insomnia, as well as aging, which are associated with learning deficits and also a reduction of deep sleep.
This research was funded by awards from the National Alliance for Research on Schizophrenia and Depression, the Milton Fund of Harvard University, and the National Institutes of Health.

Molecular biology of sleep apnea could lead to new treatments

Researchers at the University of Pennsylvania School of Medicine have provided, for the first time, a detailed look at the molecular pathways underlying sleep apnea, which affects more than twelve million Americans and could provide possible treatment for sleep apnea, according to the National Institutes of Health. Sleep apnea is a condition characterized by temporary breathing interruptions during sleep, in which disruptions can occur dozens or even hundreds of times a night.
The team found that in an animal model of sleep apnea poorly folded proteins accumulate in one compartment of a muscle nerve cell, which, under certain conditions, tells a cell to heal itself or destroy itself. The findings appear in a recent issue of the Journal of Neuroscience.
"Muscles relax as a normal part of sleep, causing the airway to close," explains senior author Sigrid C. Veasey, MD, Associate Professor of Medicine, at the Penn Center for Sleep. "But in patients with sleep apnea, oxygen levels in cells drop too low, sending an arousal signal to wake by gasping for air. This happens all night long, so patients experience bad quality sleep. In addition to problems with sleepiness, subtle peripheral neural injury occurs."
In a mouse model of sleep apnea, the researchers found that motor neurons of the jaw and face had swollen endoplasmic reticula, the part of the cell where proteins get folded properly. They surmised that misfolded proteins accumulated as the endoplasmic reticula of mice were exposed to decreased oxygen and oxygen fluctuations during sleep over eight weeks. The involvement of the endoplasmic reticula has never been shown before in explaining the physiology of sleep apnea on a cellular level, says Veasey.
But how does this work? Sensor proteins sitting on the surface of the endoplasmic reticula get activated by poorly folded proteins within. The Penn group worked with one of those proteins, called PERK. When PERK gets activated, two things can happen: The cell can take a pathway to fix itself or one that leads to self destruction. The cell makes that decision based on its initial health.
"If a patient has sleep apnea with healthy cells, the cells will take the fix-it path. Then good things happen; the cell activates another molecule called eIF-2alpha, which turns on helpful molecules like anti-oxidants that degrade the misfolded proteins," explains Veasey.
However if cells are unhealthy to begin with, the PERK pathway can also turn on molecules that cause the cell to turn on itself and activate apoptosis or cell death. "In this event, we predict that patients with sleep apnea may lose motor neurons," notes Veasey. "Eventually sleep apnea could continue to worsen since the few remaining neurons are already stressed when gasping for air during sleep."
A drug called salubrinal does keep the eIF-2alpha path active, thereby preventing vulnerable cells from going down the cell-death path. But salubrinal is a double-edged sword: Just the right amount keeps the cell happy, but too much can shut down all protein synthesis, a highly toxic outcome.
The research team is now working on how to ramp up the eIF-2alpha path with changes in the mouse diet. "This paper shows which pathways are important for treating sleep apnea, but we'll need to come up with therapies other than salubrinal," says Veasey. "Ultimately if we can do healthy things that protect the endoplasmic reticula of cells, then sleep apnea won't be such an insult, not only to motor neurons, but neurons involved in cognition and alertness.

Insomnia Drug Tasimelteon Resets Sleep, Helps Jet Lag

Results of phase II and III trials of an insomnia drug pill from Vanda Pharmaceuticals suggest that the melatonin analogue tasimelteon could be a therapeutic approach to manage transient insomnia caused by jet lag and shift work.
The way tasimelteon works is that this sleeping pill helps the body produce more of the sleep hormone melatonin may improve sleep for jet-lagged travelers and shift workers. It resets the body's natural sleep rhythm and could be in the market available for sleepless consumers within three years.
Vanda Pharmaceuticals report is published in The Lancet. The publication is entitled "Melatonin agonist tasimelteon (VEC-162) for transient insomnia after sleep-time shift: two randomised controlled multicentre trials."
In the phase II study, tasimelteon reduced sleep latency and increased sleep efficiency compared with placebo. The shift in plasma melatonin rhythm to an earlier hour was dose dependent. In the phase III study, tasimelteon improved sleep latency, sleep efficiency, and wake after sleep onset (ie, sleep maintenance). The frequency of adverse events was similar between tasimelteon and placebo.
After an abrupt advance in sleep time, tasimelteon improved sleep initiation and maintenance concurrently with a shift in endogenous circadian rhythms. Tasimelteon may have therapeutic potential for transient insomnia in circadian rhythm sleep disorders. Read: Insomnia Treatment Shows Positive Results >>
Circadian rhythm sleep disorders are common causes of insomnia for millions of individuals. We did a phase II study to establish efficacy and physiological mechanism, and a phase III study to confirm efficacy of the melatonin agonist tasimelteon (VEC-162) for treatment of transient insomnia associated with shifted sleep and wake time.
The body's circadian clock plays significant roles in regulating sleep, mood as well as cardiovascular and metabolic processes. Circadian rhythm sleep disorders include insomnia associated with shift work (overnight, rotating and early riser), travel across time zones, delayed sleep phase syndrome, advanced phase syndrome and the non-24-hour sleep-wake syndrome in the blind. These disorders represent a large public health problem and, as presented in the 2006 Institute of Medicine (IOM) report on sleep disorders, the annual economic impact of sleep problems due to night shift work alone is estimated to exceed $65 billion.
The novel circadian regulator tasimelteon holds promise for the treatment of patients with misalignments of the body clock. The work presented in The Lancet examines the potential application in sleep disorders. Additional clinical trials will have to be conducted to examine the role of circadian regulators in the treatment of other disorders such as depression, nondipper hypertension, and others.
Elizabeth Klerman, an associate professor at Harvard Medical School in Boston, in a telephone interview today told Bloomberg that "Sleeping pills take care of one of the symptoms, the difficulty you have in falling asleep. This takes care of the underlying effect by shifting your body to the right time zone."
We just returned from a trip to Europe and suffered jet lag as a result of our ten-hour Trans-Atlantic flight. I thought we could overcome it fairly soon, in a 3-4 day period, however, it took me and my family at least 7 days to fully recover from jet lag and insomnia. About 30 million Americans, the two-third of those who traveled internationally in 2007 and 20 million shift workers that work between 2AM and 7AM can benefit from Vanda's tasimelteon by helping jet lag and insomnia.
Read more about Sleep Disorders.
The article in the Lancet presents results from two clinical studies with more than 400 volunteers, who were asked to initiate sleep five hours before their usual bedtimes. Tasimelteon was shown to reset the molecular machinery of the circadian clock and restore the sleep-wake cycle by improving both the ability to initiate and to maintain sleep as compared to placebo-treated patients.
Tasimelteon works by mimicking the effects of sleep hormone Melatonin in the body. Melatonin releases a natural hormone in the brain, which plays a key role in regulating sleep. "The scientists believe that as well as offering a potential cure for jet lag and other sleep problems the drug, made by Vanda Pharmaceuticals, could also help to explain how melatonin regulates sleep patterns, " comments the Telegraph.