Tag Archives: coma

Credit: Pixabay.

GHB drug use associated with long-term cognitive changes

Credit: Pixabay.

Credit: Pixabay.

GHB, also known as “G” or “liquid ecstasy”, is a popular party drug in Europe. One of its hallmarks is that it makes people sleepy, and can easily trip users into a coma. In fact, it’s quite common to hear about GHB users who have slipped into more than two dozen comas.

GHB (gamma-hydroxybutyrate) overdose-induced comas are the third leading cause of drug-related emergency medical attention in Europe, after heroin and cocaine, and this trend is increasing. But despite the widespread recreational use of GHB, little is known about its long-term effects on health, particularly cognition.

Seeking to address this gap, researchers at the University of Amsterdam recruited 27 GHB users who have never had a coma, 27 volunteers who regularly used combinations of various drugs (but had never used GHB), and 27 GHB users who had experienced a minimum of 4 comas. To gauge the participants’ IQs, along with levels of anxiety, stress, and depression, they had to answer questions from standard questionnaires and had to perform various cognitive tasks while undergoing a fMRI brain scan.

GHB users who had never experienced a coma had problems identifying negative emotions. In addition, GHB users who had a history of comas had lower IQ scores than GHB users who did not experience comas, despite similar education levels. This group also had altered brain processes during verbal long-term memory and working memory tasks.

The study, which performed the first functional MRI scans to gauge the effect of regular GHB use and multiple GHB-induced comas, offers unique insight into the drug’s effects on human cognition. Its findings indicate that there are serious risks to long-term GHB users, particularly after overdosing.

“In an as yet unpublished study, we show that those with multiple GHB-induced comas also have 63% more stress and 23% more anxiety, and alterations in long-term memory. MRI scans also show that there are changes to the brain, with some areas showing altered brain activity and connectivity between memory-related cerebral pathways. These results show that there are brain and cognitive changes associated with multiple GHB-induced comas. Most users experience only the feeling of elation followed by drowsiness or sleep, so they don’t see that there might be any negative effects. This work indicates that might not be the case,” said lead researcher Filipa Raposo Pereira, a psychiatrist at the University of Amsterdam.

The findings suggest that recreational users should be aware of the negative associated effects of GHB. In a regulated environment, such as in medicine where it is used to treat narcolepsy, GHB does not seem to pose similar risks.

As a caveat, the study almost exclusively included males, so it may be unwise to generalize the findings to female GHB users. Secondly, this is an observational study, and no cause-effect relationship has been established. This mechanisms by which GHB may interfere with normal brain and cognitive function will hopefully be the subject of another study.

“These results suggest that GHB use is not without risk. Society is faced with increasing numbers of emergency attendances related to GHB overdose and individuals seeking treatment for GHB dependence. This suggests that awareness campaigns directed at recreational GHB users are warranted to highlight the lasting adverse effects of GHB, despite the absence of immediate apparent side effects,” the authors reported in the journal Drug and Alcohol Dependence.

The results were recently presented at the European College of Neuropsychopharmacology (ECNP) conference in Barcelona.

67P/Churyumov-Gerasimenko.

Comet 67P harbors oxygen molecules as old as the Solar System

Molecular oxygen found on the comet 67P/Churyumov-Gerasimenko isn’t produced on the surface — it comes from the early days of the Solar System.

67P/Churyumov-Gerasimenko.

Mosaic of four images taken by Rosetta’s navigation camera (NAVCAM) on 19 September 2014 at 28.6 km (17.8 mi) from the centre of comet 67P/Churyumov–Gerasimenko.
Image credits ESA / Rosetta / NAVCAM.

Between August 2014 and September 2016, the European Space (ESA) Agency’s Rosetta craft tagged along with the comet  67P/Churyumov-Gerasimenko as it was trekking around the Sun. The mission also saw a probe delivered to the comet’s surface.

Among other things, the ESA wanted to use Rosetta to study the comet’s coma — the nebulous envelope around the nucleus of a comet. This structure is created by ice subliming — turning from a solid directly into a gas — on the comet’s surface under the sun’s rays. Rosetta’s analysis of the coma revealed that it contains water, carbon monoxide and dioxide (all compounds we were expecting to find), but also molecular oxygen.

Retro oxygen

Molecular oxygen is composed of two oxygen atoms tied together by a covalent bond. Here on Earth, it’s produced by plants via photosynthesis, but researchers are well aware that oxygen is abundant in many places of the universe — we’ve detected molecular oxygen around some of Jupiter’s moons, for example. By mass, oxygen is the third-most abundant element in the universe, after hydrogen and helium — but finding it around a comet was surprising, to say the least.

With the finding also came questions regarding the origin of this molecular oxygen. Some researchers suggested that it might be produced on the comet’s surface under the action of charged ions in the solar wind.

A new paper published by members of the Rosetta team has analyzed data beamed back by the craft to get to the bottom of the issue. The research, led by researchers from the Imperial College London, found that the proposed ionic mechanism for molecular oxygen generation couldn’t account for levels of this molecule observed in the coma. This would mean that the oxygen molecules Rosetta stumbled upon are primordial — meaning they were already fully formed as the comet itself quickened during the early days of the Solar System 4.6 billion years ago.

“We tested the new theory of surface molecular oxygen production using observations of energetic ions, particles which trigger the surface processes which could lead to the production of molecular oxygen,” said lead author Mr Kevin Heritier. “We found that the amount of energetic ions present could not produce enough molecular oxygen to account for the amount of molecular oxygen observed in the coma.”

The findings don’t rule out oxygen generation at the surface level of 67P — but that the majority of the oxygen in the comet’s coma is simply not produced through such a process.

While there are other theories regarding the origin of 67P’s oxygen, the team didn’t address them in any way, either to confirm or infirm them. So far, however, they say that the primordial oxygen theory is the one which fits available data best. This is further supported by other theoretical work that treats the formation of molecular oxygen in dark clouds and the presence of molecular oxygen in the early Solar System, they add. In the team’s model, preexisting molecular oxygen froze into tiny grains that later clumped together, attracted more material, and eventually got bound up in the comet’s nucleus.

The paper “On the origin of molecular oxygen in cometary comae” has been published in the journal Nature Communications.

Vegetative state

Shock therapy partially wakes man out of 15-year-old vegetative state

A 2001 accident sent a French man into a prolonged vegetative state. He remained in this dreadful limbo for the past 15 years, until recently, when an experimental treatment proved to restore some aspects of consciousness. The patient still isn’t awake — and might never be, considering the brain damage — but his response is far more than his family or doctors could ever hope given the situation.

Vegetative state

Credit: Pixabay.

Patients in a coma and a vegetative state are both unconscious. The main difference, however, is that people in a vegetative state — also known as ‘apallic syndrome’ or ‘unresponsive wakefulness syndrome’ — still retain some sort of wakefulness, or at least they give this impression. Though involuntary, a vegetative state patient may move his limbs, grind the teeth, and make facial movements such as grimacing, yawning or smiling. They might jerk as a reflex response to loud noises or move a hand away from a source of pain. Some even make sounds.

Someone’s still there

The 35-year-old French patient has been in a prolonged vegetative state for the last 15 years with no sign of improvement since he was admitted. Angela Sirigu of the French National Centre for Scientific Research in Bron, along with colleagues, chose the patient for an experimental therapy which involved zapping his vagus nerve. This is a sort of neural hub that connects various key brain areas including the thalamus (relays sensory impulses from receptors in various parts of the body to the cerebral cortex), amygdala (paramount in our perception of fear and other emotions), and the hippocampus (where memories are stored and retrieved).

Because the vagus nerve connects so many critical brain areas thought to be heavily involved in consciousness, the researchers reckoned this would be a good place to start in order to help the man regain some of his cognitive functions.

The members of the team took their time and approached the therapy cautiously. First, they monitored the patient’s brain activity and functions for a month before lining very thin electrodes around the part of the vagus nerve located around the man’s neck. Electrical current was then directed through the electrodes for six months.

Each zap lasted 30 seconds followed by 5 minutes of rest. The current was progressively increased from 0.25 mA all the way to 1.5 mA.

Sirigu and colleagues knew they were on the right track from the very beginning. As soon as the stimulation began, the patient started opening his eye significantly more often. One month later, he would follow people moving across the room with his eyes. When doctors requested he turn his head one side or the other, the patient obeyed. He even smiled when asked to.

After vagus nerve stimulation, the metabolism increased in the right parieto-occipital cortex, thalamus and striatum. Credit: Corazzol et al.

After vagus nerve stimulation, the metabolism increased in the right parieto-occipital cortex, thalamus and striatum. Credit: Corazzol et al.

When tested on the coma recovery scale, doctors reported improvements now classing him as being in a minimally conscious state. Brain scans also show heightened activity in the various areas of the cortex following stimulation. A PET scan showed increases in metabolic activity in both cortical and subcortical regions of the brain, too, indicating increased activity.

The patient still can’t talk, walk or take care of himself in any way. Apart from following some simple instructions, the patient has yet to communicate in any meaningful way with his family or caretakers. Even so, the results are extremely promising. After all, we’re talking about a patient who for the last 15 years has shown no signs of progress. And if anything, this research shows that even when all hope seems lost, the right intervention can do wonders.

“Brain plasticity and brain repair are still possible even when hope seems to have vanished,” Sirigu said in a statement to the press.

Doctors, however, say that we shouldn’t jump to conclusions yet. The therapy involved just one patient and it’s far too early to generalize. Randomized, controlled trials in multiple locations should make things clearer, and could give hope to many people in a similar situation.

Scientific reference: Current Biology, Corazzol and Lio et al.: “Restoring consciousness with vagus nerve stimulation” http://www.cell.com/current-biology/fulltext/S0960-9822(17)30964-8.

head consciousness

The seat of consciousness might lie in two brain regions. Stimulating them could wake up patients from coma

Defining consciousness is an immense philosophical question, one that’s likely been pondered for as long as there have been humans around. Many years of contemplation over the nature of human consciousness lie ahead but, from a scientific perspective at least, we seem to be zeroing in on the biological components and mechanisms that give rise to it.

head consciousness

Credit: bykst, Pixabay

Building on decades worth of neural research, a team from Harvard Medical School and Beth Israel Deaconess Medical Center claims it has located brain regions that likely play a pivotal role in maintaining humans in a conscious state.

According to textbook neurology, consciousness is defined by two critical components: awareness and arousal. Previous research suggests the brainstem — the central trunk of the mammalian brain which is contiguous with the spinal cord and is responsible for sleep-wake cycle, but also automates respiration and heart rate — is the brain region responsible for regulating arousal. The neural systems responsible for awareness have been far more difficult to pinpoint but we do they’re somewhere in the cortex, where many of the brain’s higher functions are enabled.

Making sense of the seemingly tangled mess comprised of hundreds of billions of neurons can become a mammoth task. Which is why the researchers applied a sort of reverse engineering approach by studying patients who had brainstem lesions. Of the 36 patients involved in the study, 12 were in a coma while 24 were conscious.

Using brain scans, a map of the injured site was made for each participant which revealed that the rostral dorsolateral pontine tegmentum — a very small region of the brainstem — is strongly associated with inducing coma. Ten out of the twelve coma patients had lesions in this area, while only one of the 24 controls did.

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Using the most complex and detailed wiring diagrams of the human brain, based on a data set called the Human Connectome, it was then a matter of identifying which other parts of the brain were connected to the coma-causing lesions. Singling them out one by one, the researchers found two areas of the cortex were particularly connected to the coma-associated region of the brainstem. One was located in the left, ventral, anterior insula, the other in the pregenual anterior cingulate cortex (pACC), as reported in the journal Neurology.

Both of these regions were previously associated by other studies as being involved in arousal and awareness.

“For the first time, we have found a connection between the brainstem region involved in arousal and regions involved in awareness, two prerequisites for consciousness,” said Michael Fox, HMS assistant professor of neurology at Beth Israel Deaconess. “A lot of pieces of evidence all came together to point to this network playing a role in human consciousness.”

“We can look at not just the location of lesions, but also their connectivity,” he said. “Over the past year, researchers in my lab have used this approach to understand visual and auditory hallucinations, impaired speech and movement disorders. A collaborative team of neuroscientists and physicians had the insight and unique expertise needed to apply this approach to consciousness.”

To investigate further, a special kind of MRI machine scanned the brains of another subset of patients with consciousness disorders. In those patients with impaired consciousness, the newly identified brain network was disrupted seemingly confirming its importance in maintaining a state of awareness and arousal.

The implications of this study might be huge for the thousands of patients currently in comas. Some 90% of brain injured patients who are vegetative for one month or longer will fail to improve to a state better than severe disability if they wake up.

“The added value of thinking about coma as a network disorder is it presents possible targets for therapy, such as using brain stimulation to augment recovery,” Aaron Boes, a co-author of the new paper, said.

“This is most relevant if we can use these networks as a target for brain stimulation for people with disorders of consciousness,” said Fox. “If we zero in on the regions and network involved, can we someday wake someone up who is in a persistent vegetative state? That’s the ultimate question.”

Scientists ‘jump-start’ man’s brain after coma

Scientists have used a sonic technique to excite a man’s neurons, and the technology could one day be used to wake people up from a coma.

“It’s almost as if we were jumpstarting the neurons back into function,” says lead researcher Martin Monti.

The technology works by stimulating the thalamus, highlighted in this image. Image in public domain, via Wiki Commons.

It was a remarkable achievement, and it was the first time such a non-invasive technique was used. The technique is called low-intensity focused ultrasound pulsation, and was pioneered by Alexander Bystritsky, a UCLA professor of psychiatry and biobehavioral sciences in theSemel Institute for Neuroscience and Human Behavior. Basically, the device he created creates a small sphere of low-intensity acoustic energy at ultrasound frequencies, exciting the patient’s brain tissue. The device itself is about as big as a cup of coffee, and the amount of energy it emits is quite low. But the biggest breakthrough of this technology is that it’s non-invasive.

“Until now, the only way to achieve this was a risky surgical procedure known as deep brain stimulation, in which electrodes are implanted directly inside the thalamus,” he said. “Our approach directly targets the thalamus but is noninvasive.”

However, while the initial results were thrilling, Monti says we should wait a bit more until the technique is validated on other patients as well. He says that the first thing we should be sure of is that this wasn’t a lucky coincidence.

“It is possible that we were just very lucky and happened to have stimulated the patient just as he was spontaneously recovering,” Monti said.

The technique targets the thalamus because, in people whose mental function is deeply impaired after a coma, thalamus performance is typically diminished. In this case, the patient showed only minimal signs of being conscious and of understanding speech. In just hours, his state was improved considerably. In three days, regained full consciousness and full language comprehension, and he could reliably communicate by nodding his head “yes” or shaking his head “no.”

Because the device is so small and easy to transport, it could be incorporated into a portable “wake-up device,” helping patients in a vegetative or minimally conscious state. It’s still too early to say if the technology can truly wake people from a coma, but with the results so far, it’s hard not to get excited.

Man wakes up after 12 years of coma: “I was aware of everything”

When he was 12, Martin Pistorius came home with a sore throat. His condition quickly deteriorated and he was soon unable to move or even talk, and eventually crashed into a coma which would go on to last 12 years. It’s not clear what his disease was, and doctors don’t really know what happened to him, though the likely suspect is cryptococcal meningitis. Everybody thought he was a “vegetable”, but after 12 years in a coma, not only did he wake up – but he says he remembers everything and was perfectly conscious for most of the time. His body became his prison, but he was ultimately able to escape after spending years trying to communicate with the outside world.

Painfully aware … Martin Pistorius could hear and see everything around him but couldn’t communicate. Picture: YouTube/Thomas Nelson Source: Supplied.

According to Martin, about two years in his condition, he regained consciousness.

[Read Martin Pistorius’ book – Ghost Boy The Miraculous Escape of a Misdiagnosed Boy Trapped Inside His Own Body]

“I was aware of everything,” he said, “just like any normal person. Everyone was so used to me not being there that they didn’t notice when I began to be present again. The stark reality hit me that I was going to spend the rest of my life like that – totally alone.”

Unfortunately, there were no tests conducted on him at the time, which would have likely figured out that his brain is very much active. Martin is subject of the first episode of NPR’s new series Invisibilia.

He says that among the worst memories is the cartoon character Barney, which he was forced to watch for hours and hours straight.

‘I cannot even express to you how much I hated Barney,’ Martin recalled on the first episode of NPR’s new radio show about human behavior, Invisibilia.

Pistorius could see and even hear what was around him, but he couldn’t move. He felt as if his body was encased, and even when he started to make small movements, nobody noticed. That’s when the sadness really kicked in… and Barney was the last straw.

“You don’t really think about anything. You simply exist. It’s a very dark place to find yourself because, in a sense, you are allowing yourself to vanish.”

He was aware of important events happening in the world by hearing around him, and he was also aware that his family had continued their lives without him.

“I have a younger brother and a sister, and they and my parents would go on holidays without me, which was extremely difficult. The worst part was that I had a perpetual fear they’d have a car accident and die, and would never come to fetch me,” Pistorius told MailOnline. “I never felt angry with my parents as I knew they loved me and they did the best they could. But I felt furious about the situation. There were many times when I cried inside. I reached a point where I essentially gave up.”

Interestingly enough, it was his aromatherapist, Virna van der Walt, that picked up on his subtle “language” — virtually imperceptible smiles, gazes and nods he used to indicate he was paying attention. He was about 25.

“Happiness surged through me. I was Muhammad Ali, John McEnroe, Fred Trueman. Crowds roared their approval as I took a lap of honour,” Pistorius said of the moment his therapist acknowledged his consciousness.

She insisted that Martin should be tested, and the parents allowed this. The tests confirmed that he was awake and responsive. His parents bought him a computer with communication software, and after years and years of practice, he was able to communicate using synthetic speech. In 2003, Pistorius got a paid job at the health centre, working one day a week.

Incredible story … Martin Pistorius, 39, has regained control of his body. Picture: Facebook/Martin Pistorius Source: Supplied

“At every turn my eyes opened in wonder as I crashed into new experience: seeing a man with brightly coloured hair like parrot feathers running down the centre of his head; tasting a cloud of melting sugar called candy floss; feeling the warm pleasure that comes with going shopping for the first time to buy Christmas presents for my family; or the sharp surprise of seeing women in short skirts,” he said.

His condition started to improve, and he eventually learned how to make websites and graduated from University. He now has his own business as a web designer and is married. This truly is a stunning story, one that shows how much we still don’t understand about the comatose state, and about the human body in general.

drug coma patient

Common Anti-Anxiety drug wakes man up from coma

A patient who has been in a near-vegetative state for two years has been awaken after receiving a common anti-anxiety drug.The patient was in this state following a motorcycling accident he had, and after receiving the drug, he immediately became active, talking to his doctor, calling his aunt and congratulating his brother on graduating. Then, as quickly as he emerged from his near vegetative state, he reverted to it.

drug coma patient

Image: Maria Chiara Carboncinia et al.

The patient was a man from Pisa, Italy; he had no recollection of his accident or current status – he acted as if his normal life just resumed from yesterday. Doctors gave him the drug as a mild sedative for a CT scan, but they were shocked to see the patient waking up. To make things even stranger, as the drug wore off, the patient reverted to his previous state.

The drug in case is called midazolam. Midazolam has a wide range of effects, and it has potent anxiolytic, amnestic, hypnotic, anticonvulsant, skeletal muscle relaxant, and sedative properties; the drug is also used for the nduction and maintenance of anesthesia.

After the patient woke up and fell asleep again, the doctors gave him the drug once more, and this woke him up again.

Image: Maria Chiara Carboncinia et al

With help from EEG recordings, the neuroscientists have so far focused on activity in two regions of the brain: the task-positive network and the linguistic network.

“Our attention has focused on these two particular networks because we believe that their functional improvement has substantially contributed to determine the awakening reaction presented by our patient,” they write in the current paper. The task-positive network, in fact, has to deal with the ability to cope with and solve cognitive tasks that require explicit behavioral responses, while the linguistic one deals with language comprehension and production,” the neuroscientists explain.

This is the first time that Midazolam has been used this way. You can read the full article here.

Flat line and Nu-complex signals (credit: Daniel Kroeger et al./PLoS ONE)

Never before seen brain activity in deep coma detected

Coma patients, be it inflicted from trauma or initiated by doctors to preserve bodily functions, have their brain activity regularly monitored using electroencephalography (EEG). When in a deep coma the brain activity is described by a flat-pattern signal- basically minimal to no response, one of the limits that nearly prompts  establishing brain death. A group of physicians at University of Montreal, however, have discovered an up until now never before seen type of brain activity that kicks in after a patient’s EEG shows an isoelectric (“flat line”) EEG.

The discovery was first spurred by the findings of Dr. Bogdan Florea who was caring for a human patient in an extreme deep hypoxic (deprived of oxygen) coma under powerful anti-epileptic medication, typically used to control seizures. Instead of just a flatline, though, Florea also observed some unusual signals – anything that wasn’t flat was basically weird at this point. So Florea contacted the University of Montreal team and explained his peculiar situation.

Flat line and Nu-complex signals (credit: Daniel Kroeger et al./PLoS ONE)

Flat line and Nu-complex signals (credit: Daniel Kroeger et al./PLoS ONE)

The Montreal researchers found, after analyzing the patient’s records, “ that there was cerebral activity, unknown until now, in the patient’s brain,” said Dr. Florin Amzica. To test whether or not this was a measuring glitch of some sort, Amzica and team performed an experiment. The team recreated the initial patient’s coma state in cats (the model animal for neurological studies) by drugging them with a higher dose of isoflurane anesthetic than normal. This effectively placed the cats in a deep coma and the EEG showed the expected flat (isoelectric) EEG line. Things were all normal until then. However, after a while strong oscillations were observed.

When pinpointing their origin, the researchers found the signal’s origin was in the hippocampus, the part of the brain responsible for memory and learning processes. The researchers concluded that the observed EEG waves, or what they called “Nu-complexes,” were the same as those observed in the human patient.

Besides its peculiar nature, the finding might prove to be extremely important. For one, there are many cases in which doctors intentionally induce certain patients into coma to protect their bodies and brain. This may be technically faulty in practice. A deep coma, based on the experiment on cats, might be better suited since it preserves a certain brain activity.

“Indeed, an organ or muscle that remains inactive for a long time eventually atrophies. It is plausible that the same applies to a brain kept for an extended period in a state corresponding to a flat EEG,” says Professor Amzica.

“An inactive brain coming out of a prolonged coma may be in worse shape than a brain that has had minimal activity. Research on the effects of extreme deep coma during which the hippocampus is active is absolutely vital for the benefit of patients.”

“As these functions fade at the onset of unconsciousness, the orchestrating powers are relinquished to more basic structures such as the thalamus (in the case of sleep) or the limbic system [per the current data in the experiment],” the researchers said in the paper. “When these structures are released from neocortical influence, they begin to pursue activity patterns on their own and proceed to impose these patterns on other brain regions including the neocortex.”

Findings were reported in the journal PLoS ONE.

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