A Sleep Aid Without the Side Effects

Insomniacs desperate for some zzzs may one day have a safer way to get them. Scientists have developed a new sleep medication that has induced sleep in rodents and monkeys without apparently impairing cognition, a potentially dangerous side effect of common sleep aids. The discovery, which originated in work explaining narcolepsy, could lead to a new class of drugs that help people who don’t respond to other treatments.

Between 10% and 15% of Americans chronically struggle with getting to or staying asleep. Many of them turn to sleeping pills for relief, and most are prescribed drugs, such as zolpidem (Ambien) and eszopiclone (Lunesta), that slow down the brain by binding to receptors for GABA, a neurotransmitter that’s involved in mood, cognition, and muscle tone. But because the drugs target GABA indiscriminately, they can also impair cognition, causing amnesia, confusion, and other problems with learning and memory, along with a number of strange sleepwalking behaviors, including wandering, eating, and driving while asleep. This has led many researchers to seek out alternative mechanisms for inducing sleep.

Neuroscientist Jason Uslaner of Merck Research Laboratories in West Point, Pennsylvania, and colleagues decided to tap into the brain’s orexin system. Orexin (also known as hypocretin) is a protein that controls wakefulness and is missing in people with narcolepsy. Past studies successfully induced sleep by inhibiting orexin, but had not looked into its effects on cognition. The researchers developed a new orexin-inhibiting compound called DORA-22 and confirmed that it could induce sleep in rats and rhesus monkeys as effectively as the GABA-modulating drugs.

Then the researchers went about testing the drugs’ effects on the animals’ cognition. They measured the rats’ cognition and memory by assessing the rodents’ ability to recognize objects. They presented the rats with a new object—say, a cone or a sphere—that the rats then sniffed and explored. Then they took the object away for an hour. After that hour, the rats were exposed to a new object and the one they’d already gotten to know; if the rats remembered, they spent less time checking out the familiar object. With the primates, Uslaner’s team tested their ability to match colors on a touchscreen and to pay attention to and identify the origin of a flashing light. In all the cases, the researchers found the GABA-modulating sleeping pills caused both the rats and the primates to respond more slowly and less accurately. Monkeys taking the memory and attention tests, for example, were 20% less accurate on the highest dose of each of the GABA-modulating drugs. But DORA-22 had no such effect on cognition, the team reports today in Science Translational Medicine.

"We were very excited," Uslaner says. "Folks who take sleep medications need to be able to perform cognitive tasks when they awake, and this [compound] could help them do so without impairment."

Although DORA-22 has not yet been tested in humans, it holds tremendous promise for helping people suffering from sleep disorders, says Emmanuel Mignot, a sleep researcher with the Stanford University School of Medicine in Palo Alto, California. “This study is encouraging and exciting, because there’s good reason to believe it would work differently from what we’ve used in the past,” says Mignot, who helped discover the link between orexin (or its absence) and narcolepsy. “Not every drug works for everyone, so it’s really, really good news to have a potential new drug on the horizon.”

Scientists Decode Dreams With Brain Scans

It used to be that what happened in your dreams was your own little secret. But today scientists report for the first time that they’ve successfully decoded details of people’s dreams using brain scans.

Before you reach for your tin hat, you should know that the scientists managed this feat only with the full cooperation of their research subjects, and they only decoded dreams after the fact, not in real time. The thought police won’t be busting you for renting bowling shoes from Saddam Hussein or whatever else you’ve been up to in your dreams.

All the same, the work is yet another impressive step for researchers interested in decoding mental states from brain activity, and it opens the door to a new way of studying dreaming, one of the most mysterious and fascinating aspects of the human experience.

In the first part of the new study, neuroscientist Yukiyasu Kamitani and colleagues at the Advanced Telecommunications Research Institute International in Kyoto, Japan monitored three young men as they tried to get some sleep inside an fMRI scanner while the machine monitored their brain activity. The researchers also monitored each volunteer’s brain activity with EEG electrodes, and when they saw an EEG signature indicative of dreaming, they woke him up to ask what he’d been dreaming about.

Technically speaking, this is what researchers call ”hypnagogic imagery,” the dream-like state that occurs as people fall asleep. In the interest of saving time, Kamitani and colleagues chose to study this type of imagery rather than the dreams that tend to occur during REM sleep later in the night. They woke up each subject at least 200 times over the course of several days to build up a database of dream reports.

In the second part of the experiment, Kamitani and colleagues developed a visual imagery decoder based on machine learning algorithms. They trained the decoder to classify patterns of brain activity recorded from the same three men while they were awake and watching a video montage of hundreds of images selected from several online databases. After the decoder for each person had been trained, the researchers could input a pattern of brain activity and have the decoder predict which image was most likely to have produced that pattern of brain activity.

But that much has been done before. Where Kamitani’s team went beyond previous work was in feeding the decoder patterns of brain activity collected while the subjects were dreaming. This enabled them to correctly identify objects the men had seen in their dreams, they report Apr. 4 in Science. Or rather, they could identify the type of object a subject had seen: it could predict that a man had dreamt about a car, not that he’d been cruising around in a Maserati. And the decoder only worked when the researchers gave it a pair of possible objects to chose from (whether it was a man or a chair, for example).

“Our dream decoding is still very primitive,” Kamitani said.

Decoding color, action, or emotion is also still beyond the scope of the technology, Kamitani says. Also, it only seems to work for imagery that occurred — at most — about 15 seconds before waking up.

Finally, the decoder is unique to each person. To decode the dreams of another person, the team would have to train up a new decoder by having that person view hundreds of images.

Even so, it’s remarkable that it works as well as it does, says neuroscientist Jack Gallant of the University of California, Berkeley and a pioneer of decoding mental states from brain scans. ”It took just a huge amount of non-glamorous work to do this, and they deserve big props for that,” Gallant said.

With refinements, Gallant says the method could be useful for studying the nature and function of dreams.

“There’s the classic question of when you dream are you actively generating these movies in your head, or is it that when you wake up you’re essentially confabulating it,” Gallant said. “What this shows you is there’s at least some correspondence between what the brain is doing during dreaming and what it’s doing when you’re awake.”

Kamitani is thinking about the possibilities too. ”One theory states that dreaming is for strengthening memory, but another theory states dreaming is for forgetting,” he said. “We could record the frequency of decoded dream contents for each memory item and see the correlation between the frequency and the memory performance.”

Our internal clocks can become ticking time bombs for diabetes and obesity

New research in The FASEB Journal using mice suggests that disrupting our internal clocks can lead to a complete absence of 24-hour bodily rhythms and an immediate gain in body weight

If you’re pulling and all-nighter to finish a term paper, a new parent up all night with a fussy baby, or simply can’t sleep like you once could, then you may be snoozing on good health. That’s because new research published in The FASEB Journal used mice to show that proper sleep patterns are critical for healthy metabolic function, and even mild impairment in our circadian rhythms can lead to serious health consequences, including diabetes and obesity.

"We should acknowledge the unforeseen importance of our 24-hour rhythms for health," said Claudia Coomans, Ph.D., a researcher involved in the work from the Department of Molecular Cell Biology in the Laboratory of Neurophysiology at Leiden University Medical Center in Leiden, Netherlands. "To quote Seneca ‘We should live according to nature (secundum naturam vivere).’"

To make this discovery, Coomans and colleagues exposed mice to constant light, which disturbed their normal internal clock function, and observed a gradual degradation of their bodies’ internal clocks until it reached a level that normally occurs when aging. Eventually the mice lost their 24-hour rhythm in energy metabolism and insulin sensitivity, indicating that relatively mild impairment of clock function had severe metabolic consequences.

"The good news is that some of us can ‘sleep it off’ to avoid obesity and diabetes," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "The bad news is that we can all get the metabolic doldrums when our normal day/night cycle is disrupted."

Sleep consolidates memories for competing tasks

Sleep plays an important role in the brain’s ability to consolidate learning when two new potentially competing tasks are learned in the same day, research at the University of Chicago demonstrates.

Other studies have shown that sleep consolidates learning for a new task. The new study, which measured starlings’ ability to recognize new songs, shows that learning a second task can undermine the performance of a previously learned task. But this study is the first to show that a good night’s sleep helps the brain retain both new memories.

Starlings provide an excellent model for studying memory because of fundamental biological similarities between avian and mammalian brains, scholars wrote in the paper, “Sleep Consolidation of Interfering Auditory Memories in Starlings,” published in the current online edition of Psychological Science.

“These observations demonstrate that sleep consolidation enhances retention of interfering experiences, facilitating daytime learning and the subsequent formation of stable memories,” the authors wrote.

The paper was written by Timothy Brawn, a graduate researcher in psychology at UChicago; Howard Nusbaum, professor of psychology; and Daniel Margoliash, professor of psychology, organismal biology and anatomy. Nusbaum is a leading expert on learning, and Margoliash is a pioneer in the research of brain function and its development in birds.

Sleep loss precedes Alzheimer’s symptoms

Sleep is disrupted in people who likely have early Alzheimer’s disease but do not yet have the memory loss or other cognitive problems characteristic of full-blown disease, researchers at Washington University School of Medicine in St. Louis report March 11 in JAMA Neurology.

The finding confirms earlier observations by some of the same researchers. Those studies showed a link in mice between sleep loss and brain plaques, a hallmark of Alzheimer’s disease. Early evidence tentatively suggests the connection may work in both directions: Alzheimer’s plaques disrupt sleep, and lack of sleep promotes Alzheimer’s plaques.

“This link may provide us with an easily detectable sign of Alzheimer’s pathology,” says senior author David M. Holtzman, MD, the Andrew B. and Gretchen P. Jones Professor and head of Washington University’s Department of Neurology. “As we start to treat people who have markers of early Alzheimer’s, changes in sleep in response to treatments may serve as an indicator of whether the new treatments are succeeding.”

Sleep problems are common in people who have symptomatic Alzheimer’s disease, but scientists recently have begun to suspect that they also may be an indicator of early disease. The new paper is among the first to connect early Alzheimer’s disease and sleep disruption in humans.

(Image: iStockphoto)

Sleep Discovery Could Lead to Therapies That Improve Memory

A team of sleep researchers led by UC Riverside psychologist Sara C. Mednick has confirmed the mechanism that enables the brain to consolidate memory and found that a commonly prescribed sleep aid enhances the process. Those discoveries could lead to new sleep therapies that will improve memory for aging adults and those with dementia, Alzheimer’s and schizophrenia.

The groundbreaking research appears in a paper, “The Critical Role of Sleep Spindles in Hippocampal-Dependent Memory: A Pharmacology Study,” published in the Journal of Neuroscience.

Earlier research found a correlation between sleep spindles — bursts of brain activity that last for a second or less during a specific stage of sleep — and consolidation of memories that depend on the hippocampus. The hippocampus, part of the cerebral cortex, is important in the consolidation of information from short-term to long-term memory, and spatial navigation. The hippocampus is one of the first regions of the brain damaged by Alzheimer’s disease.

Mednick and her research team demonstrated, for the first time, the critical role that sleep spindles play in consolidating memory in the hippocampus, and they showed that pharmaceuticals could significantly improve that process, far more than sleep alone.

In addition to Mednick the research team includes: Elizabeth A. McDevitt, UC San Diego; James K. Walsh, VA San Diego Healthcare System, La Jolla, Calif; Erin Wamsley, St. Luke’s Hospital, St. Louis, Mo.; Martin Paulus, Stanford University; Jennifer C. Kanady, Harvard Medical School; and Sean P.A. Drummond, UC Berkeley.

“We found that a very common sleep drug can be used to increase verbal memory,” said Mednick, the lead author of the paper that outlines results of two studies conducted over five years with a $651,999 research grant from the National Institutes of Health. “This is the first study to show you can manipulate sleep to improve memory. It suggests sleep drugs could be a powerful tool to tailor sleep to particular memory disorders.”

(Image credit)

New study shows how seals sleep with only half their brain at a time

A new study led by an international team of biologists has identified some of the brain chemicals that allow seals to sleep with half of their brain at a time.

The study was published this month in the Journal of Neuroscience and was headed by scientists at UCLA and the University of Toronto. It identified the chemical cues that allow the seal brain to remain half awake and asleep. Findings from this study may explain the biological mechanisms that enable the brain to remain alert during waking hours and go off-line during sleep.

“Seals do something biologically amazing — they sleep with half their brain at a time. The left side of their brain can sleep while the right side stays awake. Seals sleep this way while they’re in water, but they sleep like humans while on land. Our research may explain how this unique biological phenomenon happens” said Professor John Peever of the University of Toronto.

The study’s first author, University of Toronto PhD student Jennifer Lapierre, made this discovery by measuring how different chemicals change in the sleeping and waking sides of the brain. She found that acetylcholine – an important brain chemical – was at low levels on the sleeping side of the brain but at high levels on the waking side. This finding suggests that acetylcholine may drive brain alertness on the side that is awake.

But, the study also showed that another important brain chemical – serotonin – was present at the equal levels on both sides of the brain whether the seals were awake or asleep. This was a surprising finding because scientist long thought that serotonin was a chemical that causes brain arousal.

These findings have possible human health implications because “about 40% of North Americans suffer from sleep problems and understanding which brain chemicals function to keep us awake or asleep is a major scientific advance. It could help solve the mystery of how and why we sleep” says the study’s senior author Jerome Siegel of UCLA’s Brain Research Institute.

(Image: AFP)

Paving the way for better sleep in Alzheimer’s

A new sleep pattern monitoring system has been developed by UK researchers to help spot sleep disturbance in people diagnosed with early dementia. The system, known as PAViS, could be used remotely by healthcare workers to view sleep profiles and analyse sleep patterns based on sensory data gathered at the patient’s home.

Writing in the International Journal of Computers in Healthcare, Huiru Zheng and colleagues at the University of Ulster at Jordanstown, County Antrim, Northern Ireland explain how sleep disturbance is one of the most distressing of symptoms in Alzheimer’s disease and might also be an early indicator of the onset of the disease in some cases. They point out that so-called “telecare” systems allow healthcare workers to monitor patient activity whether in normal or supported housing.

There are almost half a million people in the UK with Alzheimer’s disease and for many of those sleep disorders and disruptive nocturnal behaviour present a significant clinical problem for healthcare workers and are a cause of distress for caregivers. Sleep-related problems generally worsen as the disease progresses and are an indicator of cognitive impairment and lead to the patient being less alert than would be expected during waking hours as well as reducing their overall wellbeing.

Various systems have been developed in recent years to monitor sleeping patients. However, these would often tend to involve other people in the patient’s home as well as simply monitoring sleep patterns rather than long-term monitoring and analysis of sleep profiles for assessing sleep quality. PAViS, pattern analysis and visualisation system, circumvents the problems and allows healthcare workers to quickly see shifts in sleep pattern and detect unusual patterns in order to assess the changes in health condition of people with early dementia over the course of weeks and months. Data are collected from infrared movement detectors and sensors on bedroom and other doors in the patient’s home. This provides a non-invasive, pervasive and objective monitoring and assessment solution, the team says.

Eat to Dream: Penn Study Shows Dietary Nutrients Associated with Certain Sleep Patterns

“You are what you eat,” the saying goes, but is what you eat playing a role in how much you sleep? Sleep, like nutrition and physical activity, is a critical determinant of health and well-being. With the increasing prevalence of obesity and its consequences, sleep researchers have begun to explore the factors that predispose individuals to weight gain and ultimately obesity. Now, a new study from the Perelman School of Medicine at the University of Pennsylvania shows for the first time that certain nutrients may play an underlying role in short and long sleep duration and that people who report eating a large variety of foods – an indicator of an overall healthy diet – had the healthiest sleep patterns. The new research is published online, ahead-of-print in the journal Appetite.