How to tell if a brain is awake

EEG may not always be a reliable reflection of consciousness

December 23, 2019

Science Daily/Michigan Medicine - University of Michigan

A team was able to demonstrate, using rats, that the EEG doesn't always track with being awake. Their study raises questions about what it means to be conscious.

Remarkably, scientists are still debating just how to reliably determine whether someone is conscious. This question is of great practical importance when making medical decisions about anesthesia or treating patients in vegetative state or coma.

Currently, researchers rely on various measurements from an electroencephalogram, or EEG, to assess level of consciousness in the brain. A Michigan Medicine team was able to demonstrate, using rats, that the EEG doesn't always track with being awake.

"EEG doesn't necessarily correlate with behavior," says Dinesh Pal, Ph.D., assistant professor of anesthesiology at the U-M Medical School. "We are raising more questions and asking that people are more cautious when interpreting EEG data."

Under anesthesia, an EEG will display a sort of signature of unconsciousness: reduced brain connectivity; increased slow waves, which are also associated with deep sleep, vegetative state and coma; and less complexity or less change in brain activity over time.

Building on data from a 2018 study, Pal and his team wanted to see what happened to these measures when a brain was awakened under anesthesia. To do so, they targeted an area of the brain called the medial prefrontal cortex, which has been shown to play a role in attention, self-processing and coordinating consciousness.

Using a drug in that part of the brain that mimics the activity of neurotransmitter acetylcholine, the team was able to rouse some of the rats so that they were up and moving around despite the fact that they were receiving continuous anesthesia. Using the same drug in the back of the brain did not awaken the rats. So, both groups of rats had anesthesia in the brain but only one group "woke up."

Then, "we took the EEG data and looked at those factors that have been considered correlates of wakefulness. We figured if the animals were waking up, even while still exposed to anesthesia, then these factors should also come back up. However, despite wakeful behavior, the EEGs were the same in the moving rats and the non-moving anesthetized rats," says Pal.

What does this mean for the EEG's ability to reflect consciousness? "The study does support the possibility that certain EEG features might not always accurately capture the level of consciousness in surgical patients," says senior author George A. Mashour, M.D., Ph.D., chair of the U-M Department of Anesthesiology.

However, "EEG likely does have value in helping us understand if patients are unconscious. For example, a suppressed EEG would suggest a very high probability of unconsciousness during general anesthesia. However, using high anesthetic doses to suppress the EEG might have other consequences, like low blood pressure, that we want to avoid. So, we will have to continue to be judicious in assessing the many indices available, including pharmacologic dosing guidelines, brain activity, and cardiovascular activity."

Pal notes that there is physiological precedent for an EEG mismatching behavior; for example, the brain of someone in REM sleep is almost identical to an awake brain. "No monitor is perfect, but the current monitors we use for the brain are good and do their job most of the time. However, our data suggest there are exceptions."

Their study raises intriguing questions about how consciousness is reflected in the brain, says Pal. "These measures do have value and we have to do more studies. Maybe they are associated with awareness and what we call the content of consciousness. With rats, we don't know-we can't ask them."

https://www.sciencedaily.com/releases/2019/12/191223122837.htm

Stressed to the max? Deep sleep can rewire the anxious brain

A sleepless night can trigger up to a 30 percent rise in emotional stress levels, new study shows

https://www.sciencedaily.com/images/2019/11/191104124140_1_540x360.jpg 11-8

Deep sleep concept (stock image). Credit: © stokkete / Adobe Stock

November 4, 2019

Science Daily/University of California - Berkeley

Researchers have found that the type of sleep most apt to calm and reset the anxious brain is deep sleep, also known as non-rapid eye movement (NREM) slow-wave sleep, a state in which neural oscillations become highly synchronized, and heart rates and blood pressure drop.

When it comes to managing anxiety disorders, William Shakespeare's Macbeth had it right when he referred to sleep as the "balm of hurt minds." While a full night of slumber stabilizes emotions, a sleepless night can trigger up to a 30% rise in anxiety levels, according to new research from the University of California, Berkeley.

UC Berkeley researchers have found that the type of sleep most apt to calm and reset the anxious brain is deep sleep, also known as non-rapid eye movement (NREM) slow-wave sleep, a state in which neural oscillations become highly synchronized, and heart rates and blood pressure drop.

"We have identified a new function of deep sleep, one that decreases anxiety overnight by reorganizing connections in the brain," said study senior author Matthew Walker, a UC Berkeley professor of neuroscience and psychology. "Deep sleep seems to be a natural anxiolytic (anxiety inhibitor), so long as we get it each and every night."

The findings, published today, Nov. 4, in the journal Nature Human Behaviour, provide one of the strongest neural links between sleep and anxiety to date. They also point to sleep as a natural, non-pharmaceutical remedy for anxiety disorders, which have been diagnosed in some 40 million American adults and are rising among children and teens.

"Our study strongly suggests that insufficient sleep amplifies levels of anxiety and, conversely, that deep sleep helps reduce such stress," said study lead author Eti Ben Simon, a postdoctoral fellow in the Center for Human Sleep Science at UC Berkeley.

In a series of experiments using functional MRI and polysomnography, among other measures, Simon and fellow researchers scanned the brains of 18 young adults as they viewed emotionally stirring video clips after a full night of sleep, and again after a sleepless night. Anxiety levels were measured following each session via a questionnaire known as the state-trait anxiety inventory.

After a night of no sleep, brain scans showed a shutdown of the medial prefrontal cortex, which normally helps keep our anxiety in check, while the brain's deeper emotional centers were overactive.

"Without sleep, it's almost as if the brain is too heavy on the emotional accelerator pedal, without enough brake," Walker said.

After a full night of sleep, during which participants' brain waves were measured via electrodes placed on their heads, the results showed their anxiety levels declined significantly, especially for those who experienced more slow-wave NREM sleep.

"Deep sleep had restored the brain's prefrontal mechanism that regulates our emotions, lowering emotional and physiological reactivity and preventing the escalation of anxiety," Simon said.

Beyond gauging the sleep-anxiety connection in the 18 original study participants, the researchers replicated the results in a study of another 30 participants. Across all the participants, the results again showed that those who got more nighttime deep sleep experienced the lowest levels of anxiety the next day.

Moreover, in addition to the lab experiments, the researchers conducted an online study in which they tracked 280 people of all ages about how both their sleep and anxiety levels changed over four consecutive days.

The results showed that the amount and quality of sleep the participants got from one night to the next predicted how anxious they would feel the next day. Even subtle nightly changes in sleep affected their anxiety levels.

"People with anxiety disorders routinely report having disturbed sleep, but rarely is sleep improvement considered as a clinical recommendation for lowering anxiety," Simon said. "Our study not only establishes a causal connection between sleep and anxiety, but it identifies the kind of deep NREM sleep we need to calm the overanxious brain."

On a societal level, "the findings suggest that the decimation of sleep throughout most industrialized nations and the marked escalation in anxiety disorders in these same countries is perhaps not coincidental, but causally related," Walker said. "The best bridge between despair and hope is a good night of sleep."

https://www.sciencedaily.com/releases/2019/11/191104124140.htm

Researchers identify glial cells as critical players in brain's response to social stress

August 13, 2019

Science Daily/Advanced Science Research Center, GC/CUNY

Exposure to violence, social conflict, and other stressors increase risk for psychiatric conditions such as depression and post-traumatic stress disorder. Not everyone who experiences significant stress will develop such a response, however, and the cellular and molecular basis for an individual's underlying resilience or susceptibility to stressful events has remained poorly understood. Now, a newly published paper in the journal eLife from researchers at the Advanced Science Research Center (ASRC) at The Graduate Center, CUNY suggests that the behavior of oligodendrocytes -- the glial cells that produce the myelin sheath that protects nerve fibers -- plays a critical role in determining whether we succumb to or tolerate stress.

"Through our study, we were able to identify brain-region-specific differences in the number of mature oligodendrocytes and in the content of myelin between two groups of mice who were categorized based on their resilience or susceptibility to an identical social-defeat stressor," said the paper's corresponding author Jia Liu, a research associate professor with the ASRC's Neuroscience Initiative. "After repeated exposure to an aggressive mouse, some animals, called "susceptible," avoided any sort of social interaction with their peers, while others remained resilient and continued to be socially engaged."

In follow-up brain tissue analysis, the research team detected fewer mature oligodendrocytes and irregular myelin coverage in the medial prefrontal cortex -- a brain region that plays a critical role in emotional and cognitive processing -- in the susceptible mice. In contrast, healthy numbers of oligodendrocytes and myelin were detected in resilient mice.

Methodology

For the study, researchers exposed test mice to an aggressor for five minutes daily over 10 days. Following this period, the mice were placed in the presense of unfamiliar mouse and categorized either as susceptible if they showed signs of social withdrawal or resilient if they still showed interest in socializing with the new mouse -- a social behavior that is typically detected in normal mice.

Reseachers next sought to determine if there were myelination differences between susceptible and resilient mice. They looked at two areas of the brain that are known to play a critical role in determining the individual's response to stress. In one of those areas -- the medial prefrontal cortex -- they found that the myelinated segments of nerve fiber in susceptible mice were shorter in length and thinner than typical. They did not find this condition in the resilient or control mice groups. They also investigated the state of each mouse group's glial cells, and discovered that in susceptible mice fewer of these cells had differentiated into myelin-producing oligodendrocytes.

In a final experiment, researchers found that induced damage to the myelin in the medial prefrontal cortex caused altered social behavior in mice, but the behavior returned to normal when new myelin was formed.

"Dr. Liu's research has highlighted the importance of stressful social events in changing the epigenetic code of oligodendrocyte progenitors, which may account for the increased susceptibility to developing chronic psychiatric disorders in some individuals," said Patrizia Casaccia, founding director of the ASRC Neuroscience Initiative. "Her data suggest that oligodendrocyte progenitor differentiation can be affected by emotional and psychological events, and this provides a new concept for preventing and treating depression. Current treatments target neuronal function, but Dr. Liu's work identifies potential new therapy targets as it suggests glial cell dysfunction could be a cause of stress-related mental disorders."

https://www.sciencedaily.com/releases/2019/08/190813080212.htm