Posts tagged REM sleep

It’s a question that has long fascinated and flummoxed those who study human behavior: From whence comes the impulse to dream? Are dreams generated from the brain’s “top” — the high-flying cortical structures that allow us to reason, perceive, act and remember? Or do they come from the brain’s “bottom” — the unheralded brainstem, which quietly oversees such basic bodily functions as respiration, heart rate, salivation and temperature control?

(Source: Los Angeles Times)

A team of scientists led by Dr. Antoine Adamantidis, a researcher at the Douglas Mental Health University Institute and an assistant professor at McGill University, has released the findings from their latest study, which will appear in the October issue of the prestigious scientific journal Nature Neuroscience.

(Image: iStockphoto)

Previous studies had established an association between the activity of certain types of neurons and the phase of sleep known as REM (rapid eye movement). Researchers on the team of Dr. Antoine Adamantidis identified, for the first time, a precise causal link between neuronal activity in the lateral hypothalamus (LH) and the state of REM sleep. Using optogenetics, they were able to induce REM sleep in mice and modulate the duration of this sleep phase by activating the neuronal network in this area of the brain.

This achievement is an important contribution to the understanding of sleep mechanisms in the brains of mammals, as well as the underlying neuronal network, which is still not well understood despite recent breakthroughs in neuroscience.

Better understanding how sleep is modulated to reduce sleep disorders

“These research findings could help us better grasp how the brain controls sleep and better understand the role of sleep in humans. These results could also lead to new therapeutic strategies to treat sleep disorders along with associated neuropsychiatric problems,” stated Dr. Antoine Adamantidis, who is also the Canada Research Chair in Neural Circuits and Optogenetics.

What is REM (rapid eye movement) sleep?

There are two types of sleep: REM and non-REM sleep. In humans, non-REM sleep has four stages. REM sleep, or deep sleep, is generally associated with dreaming and is a phase when the brain is very active, even though people are in a heavy sleep, their eyes move rapidly (hence the name), and their bodies have an almost total loss of muscle tonus.
Although our understanding of the mechanisms that control the wake and sleep cycle has progressed in recent years, many frontiers remain unexplored. However, we do know that a disruption in sleep can lead to adverse effects on physical and mental health in humans.

Optogenetics, a revolutionary technology

In 2010 in the journal Nature, optogenetics was recognized as one of the coming decade’s most promising techniques to better understand brain function. This new field of research and application integrates optics and genetics methodologies to modulate the activity of neural circuits. Optogenetics involves controlling neuronal activity with light. This technique is therefore used to manipulate a specific type of cell without affecting neighbouring cells. A researcher who uses optogenetics is therefore like a conductor who decides to change the sheet music for an instrument to observe the effects, however insignificant they may seem, on the orchestra’s entire performance.

(Source: douglas.qc.ca)

Isabelle Arnulf and colleagues from the Sleep Disorders Unit at the Université Pierre et Marie Curie (UPMC) have outlined case studies of patients with Auto-Activation Deficit who reported dreams when awakened from REM sleep – even when they demonstrated a mental blank during the daytime. This paper proves that even patients with Auto-Activation Disorder have the ability to dream and that it is the “bottom-up” process that causes the dream state.

In a new paper for the neurology journal Brain, Arnulf et al compare the dream states of patients with Auto-Activation Deficit (AAD) with those of healthy, control patients. AAD is caused by bilateral damage to the basal ganglia and it is a neuro-physical syndrome characterized by a striking apathy, a lack of spontaneous activation of thought, and a loss of self-driven behaviour. AAD patients must be stimulated by their care-givers in order to take part in everyday tasks like standing up, eating, or drinking. If you were to ask an AAD patient: “what are you thinking?” they would report that they have no thoughts.

During sleep, the brain is operating on an exclusively internal basis. In REM sleep, the higher cortex areas are internally stimulated by the brainstem. When awakened, most normal subjects will remember some dreams that were associated with their previous sleep state, especially in REM sleep. Would the self-stimulation of the cortex by the brainstem be sufficient to stimulate spontaneous dreams during sleep in AAD patients?

Discovering the answer to this question would go some way to proving either the top-down or bottom-up theories of dreaming. The top-down theory stipulates that dreaming begins in higher cortex memory structures and then proceeds backwards as imagination develops during wakefulness. The bottom-up theory posits that the brainstem structures which elicit rapid eye movements and cortex activation during REM sleep result in the emotional, visual, sensory, and auditory elements of dreaming.

Thirteen patients with AAD agreed to participate in the study and record their dreams in dream diaries during the week leading up to the evaluation. These patients were compared with thirteen non-medicated, healthy control subjects. Video and sleep monitoring were performed on all twenty six participants for two consecutive nights. The first night evaluated the patient’s sleep duration, structure, and architecture of their dreams. During the second night of sleep evaluation, the researchers woke the subjects up as they entered the second non-REM sleep cycle, and again after 10 min of established REM sleep during the following sleep cycle, and asked them what they were dreaming before being woken up. The dream reports were then independently analysed and scored according to; complexity of dream, bizarreness, and elaboration.

Four of the thirteen patients with AAD reported dreaming when awakened from REM sleep, even though they demonstrated a mental blank during the daytime. This is compared to 12 out of 13 of the control patients. However, the four AAD patients’ dreams were devoid of any complex, bizarre, or emotional elements. The presence of simple yet spontaneous dreams in REM sleep, despite the absence of thoughts during wakefulness in AAD patients, supports the notion that simple dream imagery is generated by brainstem stimulation and sent to the sensory cortex. The lack of complexity in the dreams of the four AAD patients, as opposed to the complexity of the control patients’ dreams, demonstrates that the full dreaming process require these sensations to be interpreted by a higher-order cortical area.

Therefore, this study shows for the first time that it is the bottom-up process that causes the dream state.

Yet, despite the simplicity of the dreams, Isabelle Arnulf commented that the banal tasks that the AAD patients dreamt about were fascinating. For instance, Patient 10 dreamt of shaving – an activity he never initiated during the daytime without motivation from his caregivers, and an activity he could not do by himself due to severe hand dystonia. Similarly, Patient 5 dreamt about writing even though he would never write in the daytime without being invited by his caregivers to do so.

Interestingly, there were no real differences in the sleep measures between the AAD patients and the control patients apart from 46% of the AAD patients had a complete absence of sleep spindles (a burst of oscillatory brain activity visible on an EEG that occurs during stage 2 sleep). The striking absence of sleep spindles in localized lesions in the basal ganglia of these 6 AAD patients highlights the role of the pallidum and striatum in spindling activity during non-REM sleep. This is a key distinction between the AAD patients and the control patients; all thirteen control subjects displayed signs of sleep spindles.

(Source: alphagalileo.org)

Despite decades of research, little is known about the function of REM sleep, or the dreams that often accompany it. Rapid eye movements occur in most mammals, with a few exceptions like echidnas and dolphins. In humans, they be become common by the seventh month of pregnancy, and persist throughout life even in the congenitally blind. Researchers have developed techniques to perform a full electrical sleep analysis on subjects while they are simultaneously scanned inside an MRI machine. A new study in PNAS now reports that REM sleep can be distinguished from other states of consciousness by virtue of rhythmic correlations, and anticorrelations, between different areas of the brain.

Polysomnography is a comprehensive biophysical analysis used to gauge sleep state. Most of the recorded variables, like EEG, eye movements and heart rate, are electrical in nature. In addition, many other kinds of measurements are often included like body temperature, breathing rate, or blood oxygenation. Although these variables together paint a fairly reliable picture of depth of sleep, they have little to say about what might be going on in the brain during different states of consciousness.

To address this problem, the researchers in the PNAS study used blood-oxygen level dependent (BOLD) MRI to assess functional connectivity between different regions of the brain. Their main finding was that the BOLD signal time series during REM sleep showed strong correlation between the thalamus and the visual cortex, and strong anticorrelation between the thalamus a region of the brain known as the posterior cingulate gyrus. Furthermore, these relations showed clear rhythmic behavior with a relatively constant period of several seconds. This temporal scale corresponds roughly to many other phasic phenomena that are seen during REM sleep.

Some of the common electrically-recorded features of REM sleep have earned names for themselves by virtue of there uniqueness. The so-called sleep spindles and k-complexes have been associated with the cessation of emg activity, and the onset of the disconnection of the brain from the musculature. At the level specific neural systems, it has long been accepted that the major monoaminergic transmitter systems of the brain take a break during REM, while the cholinergic systems become tonically active. Monoamines are those amino-acid derived transmitters that have a single amine group like noradrenaline, serotonin or histamine.

The researchers sought to partition the brain into various sensorimotor regions, and other association areas they call the default mode network (DMN). The posterior cingulate area, together with the prefrontal cortex and inferior parietal areas are said to make up this DMN. Opposite the posterior cingulate area, on the external surface of the cortex in the inferior parietal lobe, is the angular gyrus. Lying at the top of the primary fold in the brain, this area may be said to be at the convex cusp of connectivity. In other words, axons projecting from this area have more immediate short range connectivity options available to them than perhaps anywhere else in the brain. Stroke this area out, and our most fine-grained functions—mathematical, verbal and ideological—are immediately lobotomized.

As BOLD signals change relatively slowly, and can only be measured relatively slowly, they are ultimately of limited value. Uncovering the mysteries of REM sleep, and why we dream, will require much more attention to anecdote and detail. For example, it is known binocular eye movements during REM sleep can be far from conjugate in both the vertical and horizontal planes. Those creatures that show reduced levels of REM sleep have also been shown to have a smaller corpus callosum, or frequently none at all. Something about the bilateral-binocular nature of the brain seems to feature strongly in REM sleep.

At the level of dreams, it is hard to escape the idea that they have some evolved purpose, though this is not yet within the realm of fact. Many among us have dreamt of waves or waterfalls only to awake with a crushing need to visit the bathroom. Other times we teeter at the edge of a cliff, obviously standing-in for the edge of the bed, or struggle to raise a limb to defend ourself against an imaginary foe, while in reality the limb has become hypoxic under our girth. Further removed from this base physiology, our dreams may reassemble our fears and struggles, and simultaneously exaggerate and trivialize emotional events with quizzically open-ended probes.

The synchrony and interconnection of the thalamus, only accessed at low resolution in the present study, remains of central importance in the study of conscious state. Closer inspection of sensorimotor and association areas within the thalamus itself, may continue to shed more light on these issues.

(Source: medicalxpress.com)

The strongest predictor of whether a man is developing dementia with Lewy bodies — the second most common form of dementia in the elderly — is whether he acts out his dreams while sleeping, Mayo Clinic researchers have discovered. Patients are five times more likely to have dementia with Lewy bodies if they experience a condition known as rapid eye movement (REM) sleep behavior disorder than if they have one of the risk factors now used to make a diagnosis, such as fluctuating cognition or hallucinations, the study found.

The findings were being presented at the annual meeting of the American Academy of Neurology in San Diego. REM sleep behavior disorder is caused by loss of the normal muscle paralysis that occurs during REM sleep. It can appear three decades or more before a diagnosis of dementia with Lewy bodies is made in males, the researchers say. The link between dementia with Lewy bodies and the sleep disorder is not as strong in women, they add.

"While it is, of course, true that not everyone who has this sleep disorder develops dementia with Lewy bodies, as many as 75 to 80 percent of men with dementia with Lewy bodies in our Mayo database did experience REM sleep behavior disorder. So it is a very powerful marker for the disease," says lead investigator Melissa Murray, Ph.D., a neuroscientist at Mayo Clinic in Florida.

The study’s findings could improve diagnosis of this dementia, which can lead to beneficial treatment, Dr. Murray says.

"Screening for the sleep disorder in a patient with dementia could help clinicians diagnose either dementia with Lewy bodies or Alzheimer’s disease," she says. "It can sometimes be very difficult to tell the difference between these two dementias, especially in the early stages, but we have found that only 2 to 3 percent of patients with Alzheimer’s disease have a history of this sleep disorder."

Once the diagnosis of dementia with Lewy bodies is made, patients can use drugs that can treat cognitive issues, Dr. Murray says. No cure is currently available.

Researchers at Mayo Clinic in Minnesota and Florida, led by Dr. Murray, examined magnetic resonance imaging, or MRI, scans of the brains of 75 patients diagnosed with probable dementia with Lewy bodies. A low-to-high likelihood of dementia was made upon an autopsy examination of the brain.

The researchers checked the patients’ histories to see if the sleep disorder had been diagnosed while under Mayo care. Using this data and the brain scans, they matched a definitive diagnosis of the sleep disorder with a definite diagnosis of dementia with Lewy bodies five times more often than they could match risk factors, such as loss of brain volume, now used to aid in the diagnosis. The researchers also showed that low-probability dementia with Lewy bodies patients who did not have the sleep disorder had findings characteristic of Alzheimer’s disease.

"When there is greater certainty in the diagnosis, we can treat patients accordingly. Dementia with Lewy bodies patients who lack Alzheimer’s-like atrophy on an MRI scan are more likely to respond to therapy — certain classes of drugs — than those who have some Alzheimer’s pathology," Dr. Murray says.

(Source: mayoclinic.org)

July 11, 2012

Two powerful brain chemical systems work together to paralyze skeletal muscles during rapid eye movement (REM) sleep, according to new research in the July 11 issue of The Journal of Neuroscience. The finding may help scientists better understand and treat sleep disorders, including narcolepsy, tooth grinding, and REM sleep behavior disorder.

During REM sleep — the deep sleep where most recalled dreams occur — your eyes continue to move but the rest of the body’s muscles are stopped, potentially to prevent injury. In a series of experiments, University of Toronto neuroscientists Patricia L. Brooks and John H. Peever, PhD, found that the neurotransmitters gamma-aminobutyric acid (GABA) and glycine caused REM sleep paralysis in rats by “switching off” the specialized cells in the brain that allow muscles to be active. This finding reversed earlier beliefs that glycine was a lone inhibitor of these motor neurons.

"The study’s findings are relevant to anyone who has ever watched a sleeping pet twitch, gotten kicked by a bed partner, or has known someone with the sleep disorder narcolepsy," said Dennis J. McGinty, PhD, a behavioral neuroscientist and sleep researcher at the University of California, Los Angeles, who was not involved in the study. "By identifying the neurotransmitters and receptors involved in sleep-related paralysis, this study points us to possible molecular targets for developing treatments for sleep-related motor disorders, which can often be debilitating," he said

The researchers measured electrical activity in the facial muscles responsible for chewing of sleeping rats. Brain cells called trigeminal motor neurons communicate the brain’s message to move to these muscles. Previous research suggested neurotransmitter receptors called ionotropic GABAA/glycine receptors in the motor neurons caused REM sleep paralysis. However, when the researchers blocked these receptors, REM sleep paralysis still occurred.

The researchers found that to prevent REM sleep paralysis, they had to block both the ionotropic receptors and metabotropic GABAB receptors, a different receptor system. In other words, when the motor cells were cut off from all sources of GABA and glycine, the paralysis did not occur, allowing the rats to exhibit high levels of muscle activity when their muscles should have been inactive. The data suggest the two neurotransmitters must both be present together to maintain motor control during sleep, rather than working separately.

The finding could be especially helpful for those with REM sleep disorder, a disease that causes people to act out their dreams. This can cause serious injuries to patients and others around them. It is also often an early indicator of neurodegenerative diseases, such as Parkinson’s.

"Understanding the precise mechanism behind these chemicals’ role in REM sleep disorder is particularly important because about 80 percent of people who have it eventually develop a neurodegenerative disease, such as Parkinson’s disease," study author Peever added. "REM sleep behavior disorder could be an early marker of these diseases, and curing it may help prevent or even stop their development,” he said.

Provided by University of Toronto

Source: medicalxpress.com