Posts Tagged ‘insomnia’

The Food and Drug Administration (FDA) has approved a new cranial electrotherapy stimulator (CES) device for the treatment of anxiety, depression, and insomnia.

The Cervella Cranial Electrotherapy Stimulator by Innovative Neurological Devices is operated using noise-cancelling, Bluetooth-enabled headphones and an app. The device delivers a low-level, constant current to the patient’s cranium via a pair of conductive electrodes incorporated into ear pads of the headphones.

Patients will need a prescription from a licensed healthcare provider in order to purchase the device, which will cost $695, and is due to launch at the end of March (2019).

“We hope that by incorporating treatment electrodes into a noise-cancelling headset, patient compliance will significantly increase and, consequently, treatment outcomes will improve,” said Bart Waclawik, President and CEO of Innovative Neurological Devices. “Also, by making the Cervella device appear indistinguishable from ordinary over-ear headphones, patients will have the freedom to use the device in anxiety-inducing situations without curious looks from onlookers.”

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Waclawik added that patients will be able to share treatment data with providers through the app, which provides automated data recordings and treatment reminders.

For more information visit Cervella.us.

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Illustration by Paweł Jońca

by Helen Thomson

In March 2015, Li-Huei Tsai set up a tiny disco for some of the mice in her laboratory. For an hour each day, she placed them in a box lit only by a flickering strobe. The mice — which had been engineered to produce plaques of the peptide amyloid-β in the brain, a hallmark of Alzheimer’s disease — crawled about curiously. When Tsai later dissected them, those that had been to the mini dance parties had significantly lower levels of plaque than mice that had spent the same time in the dark.

Tsai, a neuroscientist at Massachusetts Institute of Technology (MIT) in Cambridge, says she checked the result; then checked it again. “For the longest time, I didn’t believe it,” she says. Her team had managed to clear amyloid from part of the brain with a flickering light. The strobe was tuned to 40 hertz and was designed to manipulate the rodents’ brainwaves, triggering a host of biological effects that eliminated the plaque-forming proteins. Although promising findings in mouse models of Alzheimer’s disease have been notoriously difficult to replicate in humans, the experiment offered some tantalizing possibilities. “The result was so mind-boggling and so robust, it took a while for the idea to sink in, but we knew we needed to work out a way of trying out the same thing in humans,” Tsai says.

Scientists identified the waves of electrical activity that constantly ripple through the brain almost 100 years ago, but they have struggled to assign these oscillations a definitive role in behaviour or brain function. Studies have strongly linked brainwaves to memory consolidation during sleep, and implicated them in processing sensory inputs and even coordinating consciousness. Yet not everyone is convinced that brainwaves are all that meaningful. “Right now we really don’t know what they do,” says Michael Shadlen, a neuroscientist at Columbia University in New York City.

Now, a growing body of evidence, including Tsai’s findings, hint at a meaningful connection to neurological disorders such as Alzheimer’s and Parkinson’s diseases. The work offers the possibility of forestalling or even reversing the damage caused by such conditions without using a drug. More than two dozen clinical trials are aiming to modulate brainwaves in some way — some with flickering lights or rhythmic sounds, but most through the direct application of electrical currents to the brain or scalp. They aim to treat everything from insomnia to schizophrenia and premenstrual dysphoric disorder.

Tsai’s study was the first glimpse of a cellular response to brainwave manipulation. “Her results were a really big surprise,” says Walter Koroshetz, director of the US National Institute of Neurological Disorders and Stroke in Bethesda, Maryland. “It’s a novel observation that would be really interesting to pursue.”


A powerful wave

Brainwaves were first noticed by German psychiatrist Hans Berger. In 1929, he published a paper describing the repeating waves of current he observed when he placed electrodes on people’s scalps. It was the world’s first electroencephalogram (EEG) recording — but nobody took much notice. Berger was a controversial figure who had spent much of his career trying to identify the physiological basis of psychic phenomena. It was only after his colleagues began to confirm the results several years later that Berger’s invention was recognized as a window into brain activity.

Neurons communicate using electrical impulses created by the flow of ions into and out of each cell. Although a single firing neuron cannot be picked up through the electrodes of an EEG, when a group of neurons fires again and again in synchrony, it shows up as oscillating electrical ripples that sweep through the brain.

Those of the highest frequency are gamma waves, which range from 25 to 140 hertz. People often show a lot of this kind of activity when they are at peak concentration. At the other end of the scale are delta waves, which have the lowest frequency — around 0.5 to 4 hertz. These tend to occur in deep sleep (see ‘Rhythms of the mind’).

At any point in time, one type of brainwave tends to dominate, although other bands are always present to some extent. Scientists have long wondered what purpose, if any, this hum of activity serves, and some clues have emerged over the past three decades. For instance, in 1994, discoveries in mice indicated that the distinct patterns of oscillatory activity during sleep mirrored those during a previous learning exercise. Scientists suggested that these waves could be helping to solidify memories.

Brainwaves also seem to influence conscious perception. Randolph Helfrich at the University of California, Berkeley, and his colleagues devised a way to enhance or reduce gamma oscillations of around 40 hertz using a non-invasive technique called transcranial alternating current stimulation (tACS). By tweaking these oscillations, they were able to influence whether a person perceived a video of moving dots as travelling vertically or horizontally.

The oscillations also provide a potential mechanism for how the brain creates a coherent experience from the chaotic symphony of stimuli hitting the senses at any one time, a puzzle known as the ‘binding problem’. By synchronizing the firing rates of neurons responding to the same event, brainwaves might ensure that the all of the relevant information relating to one object arrives at the correct area of the brain at exactly the right time. Coordinating these signals is the key to perception, says Robert Knight, a cognitive neuroscientist at the University of California, Berkeley, “You can’t just pray that they will self-organize.”


Healthy oscillations

But these oscillations can become disrupted in certain disorders. In Parkinson’s disease, for example, the brain generally starts to show an increase in beta waves in the motor regions as body movement becomes impaired. In a healthy brain, beta waves are suppressed just before a body movement. But in Parkinson’s disease, neurons seem to get stuck in a synchronized pattern of activity. This leads to rigidity and movement difficulties. Peter Brown, who studies Parkinson’s disease at the University of Oxford, UK, says that current treatments for the symptoms of the disease — deep-brain stimulation and the drug levodopa — might work by reducing beta waves.

People with Alzheimer’s disease show a reduction in gamma oscillations5. So Tsai and others wondered whether gamma-wave activity could be restored, and whether this would have any effect on the disease.

They started by using optogenetics, in which brain cells are engineered to respond directly to a flash of light. In 2009, Tsai’s team, in collaboration with Christopher Moore, also at MIT at the time, demonstrated for the first time that it is possible to use the technique to drive gamma oscillations in a specific part of the mouse brain6.

Tsai and her colleagues subsequently found that tinkering with the oscillations sets in motion a host of biological events. It initiates changes in gene expression that cause microglia — immune cells in the brain — to change shape. The cells essentially go into scavenger mode, enabling them to better dispose of harmful clutter in the brain, such as amyloid-β. Koroshetz says that the link to neuroimmunity is new and striking. “The role of immune cells like microglia in the brain is incredibly important and poorly understood, and is one of the hottest areas for research now,” he says.

If the technique was to have any therapeutic relevance, however, Tsai and her colleagues had to find a less-invasive way of manipulating brainwaves. Flashing lights at specific frequencies has been shown to influence oscillations in some parts of the brain, so the researchers turned to strobe lights. They started by exposing young mice with a propensity for amyloid build-up to flickering LED lights for one hour. This created a drop in free-floating amyloid, but it was temporary, lasting less than 24 hours, and restricted to the visual cortex.

To achieve a longer-lasting effect on animals with amyloid plaques, they repeated the experiment for an hour a day over the course of a week, this time using older mice in which plaques had begun to form. Twenty-four hours after the end of the experiment, these animals showed a 67% reduction in plaque in the visual cortex compared with controls. The team also found that the technique reduced tau protein, another hallmark of Alzheimer’s disease.

Alzheimer’s plaques tend to have their earliest negative impacts on the hippocampus, however, not the visual cortex. To elicit oscillations where they are needed, Tsai and her colleagues are investigating other techniques. Playing rodents a 40-hertz noise, for example, seems to cause a decrease in amyloid in the hippocampus — perhaps because the hippo-campus sits closer to the auditory cortex than to the visual cortex.

Tsai and her colleague Ed Boyden, a neuro-scientist at MIT, have now formed a company, Cognito Therapeutics in Cambridge, to test similar treatments in humans. Last year, they started a safety trial, which involves testing a flickering light device, worn like a pair of glasses, on 12 people with Alzheimer’s.

Caveats abound. The mouse model of Alzheimer’s disease is not a perfect reflection of the disorder, and many therapies that have shown promise in rodents have failed in humans. “I used to tell people — if you’re going to get Alzheimer’s, first become a mouse,” says Thomas Insel, a neuroscientist and psychiatrist who led the US National Institute of Mental Health in Bethesda, Maryland, from 2002 until 2015.

Others are also looking to test how manipulating brainwaves might help people with Alzheimer’s disease. “We thought Tsai’s study was outstanding,” says Emiliano Santarnecchi at Harvard Medical School in Boston, Massachusetts. His team had already been using tACS to stimulate the brain, and he wondered whether it might elicit stronger effects than a flashing strobe. “This kind of stimulation can target areas of the brain more specifically than sensory stimulation can — after seeing Tsai’s results, it was a no-brainer that we should try it in Alzheimer’s patients.”

His team has begun an early clinical trial in which ten people with Alzheimer’s disease receive tACS for one hour daily for two weeks. A second trial, in collaboration with Boyden and Tsai, will look for signals of activated microglia and levels of tau protein. Results are expected from both trials by the end of the year.

Knight says that Tsai’s animal studies clearly show that oscillations have an effect on cellular metabolism — but whether the same effect will be seen in humans is another matter. “In the end, it’s data that will win out,” he says.

The studies may reveal risks, too. Gamma oscillations are the type most likely to induce seizures in people with photosensitive epilepsy, says Dora Hermes, a neuroscientist at Stanford University in California. She recalls a famous episode of a Japanese cartoon that featured flickering red and blue lights, which induced seizures in some viewers. “So many people watched that episode that there were almost 700 extra visits to the emergency department that day.”

A brain boost

Nevertheless, there is clearly a growing excitement around treating neurological diseases using neuromodulation, rather than pharmaceuticals. “There’s pretty good evidence that by changing neural-circuit activity we can get improvements in Parkinson’s, chronic pain, obsessive–compulsive disorder and depression,” says Insel. This is important, he says, because so far, pharmaceutical treatments for neurological disease have suffered from a lack of specificity. Koroshetz adds that funding institutes are eager for treatments that are innovative, non-invasive and quickly translatable to people.

Since publishing their mouse paper, Boyden says, he has had a deluge of requests from researchers wanting to use the same technique to treat other conditions. But there are a lot of details to work out. “We need to figure out what is the most effective, non-invasive way of manipulating oscillations in different parts of the brain,” he says. “Perhaps it is using light, but maybe it’s a smart pillow or a headband that could target these oscillations using electricity or sound.” One of the simplest methods that scientists have found is neurofeedback, which has shown some success in treating a range of conditions, including anxiety, depression and attention-deficit hyperactivity disorder. People who use this technique are taught to control their brainwaves by measuring them with an EEG and getting feedback in the form of visual or audio cues.

Phyllis Zee, a neurologist at Northwestern University in Chicago, Illinois, and her colleagues delivered pulses of ‘pink noise’ — audio frequencies that together sound a bit like a waterfall — to healthy older adults while they slept. They were particularly interested in eliciting the delta oscillations that characterize deep sleep. This aspect of sleep decreases with age, and is associated with a decreased ability to consolidate memories.

So far, her team has found that stimulation increased the amplitude of the slow waves, and was associated with a 25–30% improvement in recall of word pairs learnt the night before, compared with a fake treatment7. Her team is midway through a clinical trial to see whether longer-term acoustic stimulation might help people with mild cognitive impairment.

Although relatively safe, these kinds of technologies do have limitations. Neurofeedback is easy to learn, for instance, but it can take time to have an effect, and the results are often short-lived. In experiments that use magnetic or acoustic stimulation, it is difficult to know precisely what area of the brain is being affected. “The field of external brain stimulation is a little weak at the moment,” says Knight. Many approaches, he says, are open loop, meaning that they don’t track the effect of the modulation using an EEG. Closed loop, he says, would be more practical. Some experiments, such as Zee’s and those involving neuro-feedback, already do this. “I think the field is turning a corner,” Knight says. “It’s attracting some serious research.”

In addition to potentially leading to treatments, these studies could break open the field of neural oscillations in general, helping to link them more firmly to behaviour and how the brain works as a whole.

Shadlen says he is open to the idea that oscillations play a part in human behaviour and consciousness. But for now, he remains unconvinced that they are directly responsible for these phenomena — referring to the many roles people ascribe to them as “magical incantations”. He says he fully accepts that these brain rhythms are signatures of important brain processes, “but to posit the idea that synchronous spikes of activity are meaningful, that by suddenly wiggling inputs at a specific frequency, it suddenly elevates activity onto our conscious awareness? That requires more explanation.”

Whatever their role, Tsai mostly wants to discipline brainwaves and harness them against disease. Cognito Therapeutics has just received approval for a second, larger trial, which will look at whether the therapy has any effect on Alzheimer’s disease symptoms. Meanwhile, Tsai’s team is focusing on understanding more about the downstream biological effects and how to better target the hippocampus with non-invasive technologies.

For Tsai, the work is personal. Her grandmother, who raised her, was affected by dementia. “Her confused face made a deep imprint in my mind,” Tsai says. “This is the biggest challenge of our lifetime, and I will give it all I have.”

https://www.nature.com/articles/d41586-018-02391-6

BY DANIEL REED

Sleep deprivation majorly impacts the brain’s connectivity and function, according to a recent study published in NeuroImage. As well as affecting many important networks, sleep deprivation prevented normal changes to brain function between the morning and evening.

Sleep is an essential human state which is necessary for maintaining healthy function throughout the body. Therefore, lack of sleep has severe health-related consequences, with the brain being the most affected organ.

Lack of sleep can negatively affect memory, emotional processing and attentional capacities. For example, sleep deprivation has been shown to disrupt functional connectivity in hippocampal circuits (important for memory), and between the amygdala (important for emotion regulation) and executive control regions (involved in processes such as attention, planning, reasoning and cognitive flexibility). The emotional effects of sleep deprivation can be to both alter response patterns to negative things but also enhance reactivity toward positive things.

The study, led by Tobias Kaufmann of University of Oslo, involved 60 young men who completed three resting state functional magnetic resonance imaging (fMRI) scans – this is used to evaluate connectivity between brain regions when a person is not performing a task.

They were scanned in the morning and evening of the same day – this was to account for changes from morning to evening in normal brain function (diurnal variability). 41 men then underwent total sleep deprivation, whereas the remainder had another night of regular sleep, before they were scanned again the following morning. Finally, behavioural assessments of vigilance and visual attention were assessed.

The findings revealed that sleep deprivation strongly altered the connectivity of many resting-state networks; most clearly affected were networks important for memory (hippocampal networks) and attention (dorsal attention networks), as well as the default mode network (an interconnected set of brain regions active when a person is daydreaming or their mind is wandering).

In fact, they identified a set of 17 brain network connections showing altered brain connectivity. Furthermore, correlation analysis suggested that morning-to-evening connectivity changes returned the next day in the group that had slept the night, but not in the sleep-deprivation group.

The study emphasizes the major impact of sleep deprivation on the brain’s connectivity and function, as well as providing evidence that normal morning-to-evening connectivity changes do not occur after a night without sleep.

http://www.psypost.org/2016/07/brain-scan-research-shows-lack-sleep-severely-alters-brain-function-43977#prettyPhoto

We have all experienced the aftermath of a bad night’s sleep: grogginess, irritability, difficulty carrying out even the simplest of tasks. A growing amount of research suggests that not getting enough shut-eye could also have insidious effects on heart disease, obesity and other conditions.

The American Academy of Sleep Medicine, the largest physician-based organization for sleep medicine, recently put out their first recommendations for what is the right amount of sleep. It advises that adults get at least seven hours every night based on research on the link between inadequate sleep and a number of poor health outcomes.

Although most of us already know that we should get at least seven hours of sleep, a study last month suggested that Americans are creeping down to that cutoff. The average amount of sleep that they reported getting a night has dropped from 7.4 hours in 1985 to 7.29 hours in 1990 to 7.18 in 2004 and 2012.

The Centers for Disease Control and Prevention, which requested and helped support the development of the current recommendations, has called not getting enough sleep a public health epidemic.

For many aspects of health, “it was quite clear that seven to nine hours was good,” said Dr. Nathaniel F. Watson, president of the American Academy of Sleep Medicine and a professor of neurology at University of Washington. Watson led the panel of experts that wrote the recommendations. The group looked at more than 300 studies.

Getting only six hours of sleep a night or less was associated with setbacks in performance, including mental alertness and driving ability, and increased risk of heart attack, stroke, diabetes and obesity, Watson said.

There were not enough studies looking at the health of people who got between six and seven hours of sleep or more than nine hours to know how their health fared.

The panel did not put an upper cutoff on the amount of sleep a person should get because, in addition to the lack of evidence, “there are instances where a person might sleep longer if they are recovering from a sleep debt or illness, and we had trouble coming up with a biological way that sleep would be bad for you,” Watson said.

Although there have been reports that sleeping nine hours or more a night is associated with increased risk of death, that link probably has more to do with the fact that the people who slept a lot had underlying illnesses that ultimately did them in, said James Gangwisch, a sleep researcher at Columbia University who helped develop the current recommendations.

In addition, reports of sleeping a lot may actually be an indicator that a person is not exercising or socializing, which can carry health risks.

Sleep and how it relates to body mass and more

The panel looked at studies that reported connections between the amount of sleep that people said they got and their health over long periods. The panel also took into consideration studies that monitored people in sleep labs that controlled how much sleep they got.

For example, Gangwisch and his colleagues have reported a connection between getting less than seven hours of sleep a night and high body mass index. Separate studies in sleep labs suggest how inadequate sleep could lead to obesity: it drives up the levels of appetite-inducing hormones.

The weight gain that might be caused by inadequate shut-eye could, in turn, increase the risk of heart attack and stroke, Gangwisch said. In addition, sleep deficits seem to increase blood pressure as several studies have found, which could be bad for heart health.

One small study found that healthy adults had higher blood pressure after a night when they were only allowed to sleep four hours compared with a night when they were allowed to sleep for eight hours.

It is hard to say, however, if depriving people of sleep for an extended period would have lasting effects on blood pressure and appetite, even though studies linking sleep deprivation with heart disease and weight gain suggest so.

Sleep lab studies usually only investigate the effect of abridged snoozing for several nights, but people might adjust somewhat to sleep deprivation if it became the norm for them, Gangwisch said.

Although the recent recommendations are for the appropriate amount of shut-eye, getting bad sleep could be just as harmful as not getting enough sleep. Among the most common sleep disorders are insomnia and obstructive sleep apnea, which causes people to stop breathing intermittently throughout the night. About 10% of adults have chronic insomnia; obstructive sleep apnea affects an estimated 24% of men and 9% of women.

Obstructive sleep apnea in particular can take a toll in many ways beyond just shortening the amount of sleep you get, Watson said. The condition can increase blood pressure (separately from the effect of not getting enough sleep), deprive the body of oxygen, cause irregular heartbeat and make the blood more sticky, all of which can increase the risk of heart disease and stroke, he said.

A study that was presented this week at the European Society of Cardiology meeting found that men who had a sleep disorder were between 2 and 2.6 times more likely to have a heart attack and 1.5 to 4 times more likely to have a stroke over the 14-year period of the study.

Not sleeping well? Talk to the doc

“This study underscores to me the importance that if a person doesn’t think they are sleeping well, they should talk to their doctor,” said Kristen Knutson, an assistant professor of medicine at the University of Chicago who was not involved in the study.

Signs that you are not sleeping well or enough include needing a lot of caffeine to get through the day and falling asleep during a meeting or movie, which Knutson said does not usually happen in well-rested people no matter how bored they are.

ome people might need more or less than seven hours of shut-eye. To know what is right for you, see how long you sleep when you are a couple of days into a vacation and the alarm does not go off, Knutson suggested. (The first couple of days you might sleep longer because you are catching up.)

Knutson agrees with the advice that there does not seem to be a danger in sleeping too much. “People generally don’t sleep more than they should, and if you are laying in bed and can’t sleep, the general recommendation is to get up,” she said.

There are a number of strategies for making the most of your slumber. These include going to sleep and waking up about the same time every day, making your bedroom dark and cool and avoiding caffeine too close to bedtime.

“Some people view sleep as an obstruction to success, and we would rather have people view it as a tool for success,” Watson said. “We really want people to prioritize their sleep and understand that it is as important to their overall well being as diet and exercise,” he added.

http://www.cnn.com/2015/06/19/health/sleep-or-die/index.html