Category: Neurology

Memory Loss and Confusion More Common among Middle-aged Smokers

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Middle-aged smokers are much more likely to report having memory loss and confusion than nonsmokers, and the likelihood of cognitive decline is lower for those who have quit, even recently, according to a new study appearing in the Journal of Alzheimer’s Disease.

The study is the first to examine the relationship between smoking and cognitive decline using a one-question self-assessment asking people if they’ve experienced worsening or more frequent memory loss and/or confusion.

The findings build on previous research that established relationships between smoking and Alzheimer’s Disease and other forms of dementia, and could point to an opportunity to identify signs of trouble earlier in life, said Jenna Rajczyk, lead author of the study.

It’s also one more piece of evidence that quitting smoking is good not just for respiratory and cardiovascular reasons, but to preserve neurological health, said Rajczyk, a PhD student in Ohio State’s College of Public Health, and senior author Jeffrey Wing, assistant professor of epidemiology.

“The association we saw was most significant in the 45–59 age group, suggesting that quitting at that stage of life may have a benefit for cognitive health,” Wing said. A similar difference wasn’t found in the oldest group in the study, which could mean that quitting earlier affords people greater benefits, he said.

Researchers used data from the 2019 Behavioral Risk Factor Surveillance System Survey to compare subjective cognitive decline (SCD) measures for current smokers, recent former smokers, and those who had quit years earlier. The analysis included 136 018 people 45 and older, and about 11% reported SCD.

The prevalence of SCD among smokers in the study was almost 1.9 times that of nonsmokers. The prevalence among those who had quit less than 10 years ago was 1.5 times that of nonsmokers. Those who quit more than a decade before the survey had an SCD prevalence just slightly above the nonsmoking group.

“These findings could imply that the time since smoking cessation does matter, and may be linked to cognitive outcomes,” Rajczyk said.

The simplicity of SCD, a relatively new measure, could lend itself to wider applications, she said.

“This is a simple assessment that could be easily done routinely, and at younger ages than we typically start to see cognitive declines that rise to the level of a diagnosis of Alzheimer’s Disease or dementia,” Rajczyk said. “It’s not an intensive battery of questions. It’s more a personal reflection of your cognitive status to determine if you’re feeling like you’re not as sharp as you once were.”

Many people don’t have access to more in-depth screenings, or to specialists, making the potential applications for measuring SCD even greater, she said.

Wing said it’s important to note that these self-reported experiences don’t amount to a diagnosis, nor do they confirm independently that a person is experiencing decline out of the normal ageing process. But, he said, they could be a low-cost, simple tool to consider employing more broadly.

Source: Ohio State University

Greater Cognitive Skills in Children who Play More Video Games

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Analysing magnetic resonance imaging (MRI) brain scans of nearly 2000 children, researchers found children who played video games for three or more hours a day did better in cognitive skills tests involving impulse control and working memory compared to children who had never played video games. Published in JAMA Network Open, this study analysed data from the ongoing Adolescent Brain Cognitive Development (ABCD) Study, which is supported by the and other entities of the National Institutes of Health.

“This study adds to our growing understanding of the associations between playing video games and brain development,” said National Institute on Drug Abuse (NIDA) Director Nora Volkow, MD. “Numerous studies have linked video gaming to behaviour and mental health problems. This study suggests that there may also be cognitive benefits associated with this popular pastime, which are worthy of further investigation.”

Although a number of studies have investigated the relationship between video gaming and cognitive behaviour, the neurobiological mechanisms underlying the associations are not well understood. Only a handful of neuroimaging studies have addressed this topic, and the sample sizes for those studies have been small, with fewer than 80 participants.

To address this research gap, scientists at the University of Vermont, Burlington, analysed data obtained when children entered the ABCD Study at ages 9 and 10 years old. The research team examined survey, cognitive, and brain imaging data from nearly 2000 participants from within the bigger study cohort, comparing those who reported playing no video games at all and those who reported playing video games for three hours per day or more. This threshold was selected as it exceeds the American Academy of Paediatrics screen time guidelines, which recommend limiting videogames to one to two hours per day for older children. Researchers assessed their performance in two tasks that reflected the children’s ability to control impulsive behaviour and to memorise information, as well as brain activity while performing the tasks.

The researchers found that the children who reported playing video games for three or more hours per day were faster and more accurate on both cognitive tasks than those who never played. They also observed that the differences in cognitive function observed between the two groups was accompanied by differences in brain activity. Functional MRI brain scans found that children who played video games for three or more hours per day showed higher brain activity in regions of the brain associated with attention and memory than in never-gamers. At the same time, those children who played at least three hours of videogames per day showed more brain activity in frontal brain regions that are associated with more cognitively demanding tasks and less brain activity in brain regions related to vision.  

The researchers think these patterns may stem from practicing tasks related to impulse control and memory while playing videogames, which can be cognitively demanding, and that these changes may lead to improved performance on related tasks. Furthermore, the comparatively low activity in visual areas among children who reported playing video games may reflect that this area of the brain may become more efficient at visual processing as a result of repeated practice through video games.

While prior studies have reported associations between video gaming and increases in depression, violence, and aggressive behaviour, this study did not find that to be the case. The three hours or more group tended to report higher mental health and behavioural issues compared to the non-gaming children, but was not statistically significant. The researchers note that this will be an important measure to continue to track and understand as the children mature.

Further, the researchers stress that this cross-sectional study does not allow for cause-and-effect analyses, and that it could be that children who are good at these types of cognitive tasks may choose to play video games. The authors also emphasise that their findings do not mean that children should spend unlimited time on their computers, mobile phones, or TVs, and that the outcomes likely depend largely on the specific activities children engage in. For instance, they hypothesise that the specific genre of video games, such as action-adventure, puzzle solving, sports, or shooting games, may have different effects for neurocognitive development, and this level of specificity on the type of video game played was not assessed by the study.

“While we cannot say whether playing video games regularly caused superior neurocognitive performance, it is an encouraging finding, and one that we must continue to investigate in these children as they transition into adolescence and young adulthood,” said Bader Chaarani, PhD, assistant professor of psychiatry at the University of Vermont and the lead author on the study. “Many parents today are concerned about the effects of video games on their children’s health and development, and as these games continue to proliferate among young people, it is crucial that we better understand both the positive and negative impact that such games may have.”

Through the ABCD Study, researchers will be able to track these children into young adulthood, looking for gaming-related changes in cognitive skills, brain activity, behaviour, and mental health.

Source: National Institutes of Health

Improving Short Term Memory Problems – with Laser Light

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UK and Chinese scientists have demonstrated that laser light therapy is effective in improving short term memory in a study published in Science Advances. The innovative, non-invasive therapy could improve short term, or working memory in people by up to 25%.

The treatment, termed transcranial photobiomodulation (tPBM), is applied to the right prefrontal cortex, an area important for working memory. In their experiment, the team showed how working memory improved among research participants after several minutes of treatment. They were also able to track the changes in brain activity using electroencephalogram (EEG) monitoring during treatment and testing.

Previous studies have shown that laser light treatment will improve working memory in mice, and human studies have shown tPBM treatment can improve accuracy, speed up reaction time and improve high-order functions such as attention and emotion. This is the first study, however, to confirm a link between tPBM and working memory in humans.

Co-author Dongwei Li, a visiting PhD student, said, “People with conditions like ADHD (attention deficit hyperactivity disorder) or other attention-related conditions could benefit from this type of treatment, which is safe, simple and non-invasive, with no side-effects.”

In the study researchers at Beijing Normal University carried out experiments with 90 male and female participants aged between 18 and 25. Participants were treated with laser light to the right prefrontal cortex at wavelengths of 1064 nm, while others were treated at a shorter wavelength, or treatment was delivered to the left prefrontal cortex. Each participant was also treated with a sham, or inactive, tPBM to rule out the placebo effect.

After tPBM treatment over 12 minutes, the participants were asked to remember the orientations or colour of a set of items displayed on a screen. The participants treated with laser light to the right prefrontal cortex at 1064 nm showed clear improvements in memory over those who had received the other treatments. While participants receiving other treatment variations were about to remember between three and four of the test objects, those with the targeted treatment were able to recall between four and five objects.

Data, including from electroencephalogram (EEG) monitoring during the experiment was analysed at the University of Birmingham and showed changes in brain activity that also predicted the improvements in memory performance.

The researchers do not yet know precisely why the treatment results in positive effects on working memory, nor how long the effects will last. Further research is planned to investigate these aspects.

Professor Ole Jensen, also at the Center for Human Brain Health, said, “We need further research to understand exactly why the tPBM is having this positive effect, but it’s possible that the light is stimulating the astrocytes –the powerplants – in the nerve cells within the prefrontal cortex, and this has a positive effect on the cells’ efficiency. We will also be investigating how long the effects might last. Clearly if these experiments are to lead to a clinical intervention, we will need to see long-lasting benefits.”

Source: University of Birmingham

Scientists Unravel The Neurology Underlying Soothing Touch

Man wearing mask with headache
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People can achieve some pain relief by rubbing or pressing a part of their body associated with the pain. Observing for the first time how this phenomenon plays out in the brains of mice, MIT scientists suggest that pain-responsive cells in the brain quiet down when these neurons also receive touch inputs.

The team’s discovery, reported in the journal Science Advances, offers researchers a deeper understanding of the complicated relationship between pain and touch and could offer some insights into chronic pain in humans. “We’re interested in this because it’s a common human experience,” says investigator Fan Wang. “When some part of your body hurts, you rub it, right? We know touch can alleviate pain in this way.” But, she says, the phenomenon has been very difficult for neuroscientists to study.

Modelling pain relief

The spinal cord may be where touch-mediated pain relief begins, as prior studies have found pain-responsive neurons that reduce activity in response to touch. But there have been hints that the brain was involved, too. Wang says this aspect of the response has been largely unexplored, because it can be hard to monitor the brain’s response to painful stimuli amidst all the other neural activity happening there. particularly when an animal moves.

So while her team knew that mice respond to a potentially painful stimulus on the cheek by wiping their faces with their paws, they couldn’t follow the specific pain response in the animals’ brains to see if that rubbing helped settle it down. “If you look at the brain when an animal is rubbing the face, movement and touch signals completely overwhelm any possible pain signal,” Wang explains.

She and her colleagues have found a way around this obstacle. Instead of studying the effects of face-rubbing, they have focused their attention on a subtler form of touch: the gentle vibrations produced by the movement of the animals’ whiskers. Mice use their whiskers to explore, moving them back and forth in a rhythmic motion known as whisking to feel out their environment. This motion activates touch receptors in the face and sends information to the brain in the form of vibrotactile signals. The human brain receives the same kind of touch signals when a person shakes their hand as they pull it back from a painfully hot pan — another way we seek touch-mediate pain relief.

Whisking away pain

Wang and her colleagues found that this whisker movement alters the way mice respond to bothersome heat or a poke on the face – both of which usually lead to face rubbing. “When the unpleasant stimuli were applied in the presence of their self-generated vibrotactile whisking … they respond much less,” she says. Sometimes, she says, whisking animals entirely ignore these painful stimuli.

In the brain’s somatosensory cortex, where touch and pain signals are processed, the team found signalling changes that seem to underlie this effect. “The cells that preferentially respond to heat and poking are less frequently activated when the mice are whisking,” Wang says. “They’re less likely to show responses to painful stimuli.” Even when whisking animals did rub their faces in response to painful stimuli, the team found that neurons in the brain took longer to adopt the firing patterns associated with that rubbing movement. “When there is a pain stimulation, usually the trajectory the population dynamics quickly moved to wiping. But if you already have whisking, that takes much longer,” Wang says.

Wang notes that even in the fraction of a second before provoked mice begin rubbing their faces, when the animals are relatively still, it can be difficult to sort out which brain signals are related to perceiving heat and poking and which are involved in whisker movement. Her team developed computational tools to disentangle these, and are hoping other neuroscientists will use the new algorithms to make sense of their own data.

Whisking’s effects on pain signalling seem to depend on dedicated touch-processing circuitry that sends tactile information to the somatosensory cortex from the ventral posterior thalamus. When that pathway was blocked, whisking no longer dampened the animals’ response to painful stimuli. Now, Wang says, she and her team are eager to learn how this circuitry works with other parts of the brain to modulate the perception and response to painful stimuli.

The new findings might shed light on a condition called thalamic pain syndrome, a chronic pain disorder that can develop in patients after a stroke that affects the brain’s thalamus, says Wang. “Such strokes may impair the functions of thalamic circuits that normally relay pure touch signals and dampen painful signals to the cortex.”

Source: MIT

Hyperbaric Therapy Reduces Neuroinflammation in Autism

Depiction of a human brain
Image by Fakurian Design on Unsplash

A new study at Tel Aviv University showed significant improvements in social skills and the condition of the autistic brain through hyperbaric therapy. The study which is reported in the journal International Journal of Molecular Sciences, was conducted on lab models of autism.

Hyperbaric medicine, where patients sit in special high-pressure chambers while breathing pure oxygen, is considered safe and, besides treating decompression sickness in divers, is already in use for other conditions. The use of hyperbaric medicine to treat autism is contentious, with many holding that it is based on pseudoscience. In recent years, scientific evidence has been accumulating that unique protocols of hyperbaric treatments improve the supply of blood and oxygen to the brain, thereby improving brain function.

Changes observed in the brain included a reduction in neuroinflammation, which is known to be associated with autism. A significant improvement was also found in the social functioning of the animal models treated in the pressure chamber. The study’s success has many implications regarding the applicability and understanding of treating autism using pressure chamber therapy.

The breakthrough was led by doctoral student Inbar Fischer, from the laboratory of Dr Boaz Barak of Tel Aviv University.

Improved brain function

“The medical causes of autism are numerous and varied, and ultimately create the diverse autistic spectrum with which we are familiar,” explains Dr Barak. “About 20% of autistic cases today are explained by genetic causes, that is, those involving genetic defects, but not necessarily ones that are inherited from the parents. Despite the variety of sources of autism, the entire spectrum of behavioural problems associated with it are still included under the single broad heading of ‘autism,’ and the treatments and medications offered do not necessarily correspond directly to the reason why the autism developed.”

In the preliminary phase of the study, a girl carrying the mutation in the SHANK3 gene, which is known to lead to autism, received treatments in the pressure chamber, conducted by Prof Shai Efrati. After the treatments, it was evident that the girl’s social abilities and brain function had improved considerably.

In the next stage, and in order to comprehend the success of the treatment more deeply, the team of researchers at Dr Barak’s laboratory sought to understand what being in a pressurised chamber does to the brain. To this end, the researchers used lab models carrying the same genetic mutation in the SHANK3 gene as that carried by the girl who had been treated. The experiment comprised a protocol of 40 one-hour treatments in a pressure chamber over several weeks.

“We discovered that treatment in the oxygen-enriched pressure chamber reduces inflammation in the brain and leads to an increase in the expression of substances responsible for improving blood and oxygen supply to the brain, and therefore brain function,” explains Dr Barak. “In addition, we saw a decrease in the number of microglial cells, immune system cells that indicate inflammation, which is associated with autism.”

Increased social interest

“Beyond the neurological findings we discovered, what interested us more than anything was to see whether these improvements in the brain also led to an improvement in social behaviour, which is known to be impaired in autistic individuals,” adds Dr Barak. “To our surprise, the findings showed a significant improvement in the social behaviour of the animal models of autism that underwent treatment in the pressure chamber compared to those in the control group, who were exposed to air at normal pressure, and without oxygen enrichment. The animal models that underwent treatment displayed increased social interest, preferring to spend more time in the company of new animals to which they were exposed in comparison to the animal models from the control group.”

Inbar Fischer concludes, “the mutation in the animal models is identical to the mutation that exists in humans. Therefore, our research is likely to have clinical implications for improving the pathological condition of autism resulting from this genetic mutation, and likely also of autism stemming from other causes. Because the pressure chamber treatment is non-intrusive and has been found to be safe, our findings are encouraging and demonstrate that this treatment may improve these behavioral and neurological aspects in humans as well, in addition to offering a scientific explanation of how they occur in the brain.”

Source: Tel Aviv University

How Breathing Influences the Brain to Shape Mood and Behaviour

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A study published in the journal Psychological Review describes a possible mechanism by which breathing influences the brain and how breathing exercises influence mood. The researchers synthesised results from more than a dozen studies with rodent, monkey, and human brain imaging, and used it to propose a new computational model that explains how our breathing influences the brain’s expectations.

“What we found is that, across many different types of tasks and animals, brain rhythms are closely tied to the rhythm of our breath. We are more sensitive to the outside world when we are breathing in, whereas the brain tunes out more when we breathe out. This also aligns with how some extreme sports use breathing, for example professional marksmen are trained to pull the trigger at the end of exhalation,” explains Professor Micah Allen from the Department of Clinical Medicine at Aarhus University.

The study suggest that breathing is more than just something we do to stay alive, explains Prof Allen.

“It suggests that the brain and breathing are closely intertwined in a way that goes far beyond survival, to actually impact our emotions, our attention, and how we process the outside world. Our model suggests there is a common mechanism in the brain which links the rhythm of breathing to these events.”

Breathing can affect our mental health

Understanding how breathing shapes our brain, and by extension, our mood, thoughts, and behaviours, is an important goal in order to better prevent and treat mental illness.

“Difficulty breathing is associated with a very large increase in the risk for mood disorders such as anxiety and depression. We know that respiration, respiratory illness, and psychiatric disorders are closely linked. Our study raises the possibility that the next treatments for these disorders might be found in the development of new ways to realign the rhythms of the brain and body, rather than treating either in isolation,” explains Micah Allen.

The new study sheds light on how the brain its possible to stabilise the mind through breathing exercises. It suggests that there are three pathways in the brain that control this interaction between breathing and brain activity. It also suggests that our pattern of breathing makes the brain more “excitable,” meaning neurons are more likely to fire during certain times of breathing.

Prof Allen says that research is underway into investigating how different kinds of emotional and visual perception are influenced by breathing in the brain, as well as the impact of long COVID.

Source: Aarhus University

Hormonal Contraceptives’ Impacts on the Adolescent Brain

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Hormonal contraceptives are safe and highly effective at preventing pregnancy, but their impact on the developing bodies of teenage girls, especially their brains, is not well understood.

New research in young rats links the synthetic hormones found in birth control pills, patches and injections with disordered signal transmission between cells in the prefrontal cortex, which is still developing during adolescence. Compared to control rats, the animals receiving hormonal contraceptives also produced higher levels of the stress hormone corticosterone, which is similar to cortisol in humans.

The Ohio State University scientists began investigating the prefrontal cortex, where mood is regulated, because some previous research has associated early adolescent use of hormonal contraceptives with adulthood depression risk. But the most important thing, the researchers said, is learning how birth control affects the developing brain so individuals can weigh the risks and benefits of their reproductive health choices.

“Birth control has had a major positive impact for women’s health and autonomy – so it’s not that we’re suggesting adolescents should not take hormonal contraceptives,” said senior study author Benedetta Leuner, associate professor of psychology at Ohio State.

“What we need is to be informed about what synthetic hormones are doing in the brain so we can make informed decisions – and if there are any risks, then that’s something that needs to be monitored. Then if you decide to use hormonal birth control, you would pay more attention to warning signs if you knew of any possible mood-related side effects.”

The research poster was presented to at Neuroscience 2022, the annual meeting of the Society for Neuroscience.

An estimated 2 in 5 teenage girls in the US have sexual intercourse between age 15 and 19, and the vast majority use a contraceptive, mostly condoms. Of those using birth control, almost 5% use hormonal contraceptives, also known as long-acting reversible contraceptives. These products are also prescribed to treat acne and heavy periods.

Despite their popularity, “there isn’t a lot known about how hormonal birth control influences the teen brain and behaviour,” said co-author Kathryn Lenz, associate professor of psychology at Ohio State. “Adolescence is a crucially under-investigated period of dramatic brain change and dramatic hormonal change that we really haven’t understood.”

The researchers gave a combination of synthetic estrogen and progesterone typically found in hormonal contraceptives to female rats for three weeks beginning about a month after they were born, an age equivalent to early adolescence in humans. Researchers confirmed the drugs disrupted the animals’ reproductive cycling — these birth control products work by stopping ovaries from producing hormones at levels necessary to generate eggs and making the uterine lining inhospitable for an egg to implant.

Blood samples showed the treated rats were producing more corticosterone than untreated animals, a sign that they were stressed. And after being subjected to and recovering from an experimental stressor, the treated rats’ corticosterone level remained high. Their adrenal glands were also larger, suggesting their stress hormone production was consistently higher than that of control animals.

An analysis of gene activation markers in the animals’ prefrontal cortex showed a decrease in excitatory synapses in that region of treated rats’ brains compared to controls, but no change to inhibitory synapses — a phenomenon that could set up an imbalance of normal signaling patterns and result in altered behavior. The loss of only excitatory synapses in the prefrontal cortex has been linked to exposure to chronic stress and depression in previous research.

“What this means for the function of particular circuits, we don’t know yet. But this gives us a clue of where to look next in terms of what the functional outcomes might be,” Lenz said.

The researchers are moving forward with additional studies targeting hormonal contraceptive effects on the brain between puberty and late adolescence – a tricky time to study the developing brain because it is undergoing constant change, Leuner said. The reasons behind the drugs’ effects are an open question, as well.

“These are synthetic hormones, so are they affecting the brain because of their synthetic properties, or are they affecting the brain because they’re blocking the naturally produced hormones?” she said. “It’s a difficult question to answer, but an important one.”

Source: Ohio State University

Exploring the Avoidance of Eye Contact in Autism

A reluctance to make eye contact is a hallmark of autism spectrum disorder (ASD). By simultaneously imaging the brains of people making eye contact, Yale University researchers found that eye contact between two individuals was associated with a specific area associated with social interaction, which synchronises when two people with normal neural development gaze at each other. The results, published in the journal PLOS ONE, showed that in people with ASD, there was less activity in this region when they attempted eye contact.

People with ASD have been showed to have reduced or altered neurological arousal from looking at images of faces or even robots. Although eye contact is a critically important part of social interactions, scientists have been limited in studying the neurological basis of live social interaction with eye-contact in ASD because of the inability to image the brains of two people simultaneously.

Now, using an innovative technology that enables imaging of two individuals during live and natural conditions, Yale researchers have identified specific brain areas in the dorsal parietal region of the brain associated with the social symptomatology of autism. The study finds that these neural responses to live face and eye-contact may provide a biomarker for the diagnosis of ASD as well as provide a test of the efficacy of treatments for autism.

“Our brains are hungry for information about other people, and we need to understand how these social mechanisms operate in the context of a real and interactive world in both typically developed individuals as well as individuals with ASD,” said co-corresponding author Joy Hirsch, Elizabeth Mears and House Jameson Professor of Psychiatry, Comparative Medicine, and of Neuroscience at Yale.

The Yale team, led by Hirsch and James McPartland, Harris Professor at the Yale Child Study Center, analysed brain activity during brief social interactions between pairs of adults – each including a typical participant and one with ASD – using functional near-infrared spectroscopy, a non-invasive optical neuroimaging method. Both participants were fitted with neuroimaging caps which measured brain activity during face gaze and eye-to-eye contact.

The investigators found that during eye contact, participants with ASD had significantly reduced activity in a brain region called the dorsal parietal cortex compared to those without ASD. Further, the more severe the overall social symptoms of ASD as measured by ADOS (Autism Diagnostic Observation Schedule, 2nd Edition) scores, the less activity was observed in this brain region. Neural activity in these regions was synchronous between typical participants during real eye-to-eye contact but not during gaze at a video face. This typical increase in neural coupling was not observed in ASD, and is consistent with the difficulties in social interactions.

“We now not only have a better understanding of the neurobiology of autism and social differences, but also of the underlying neural mechanisms that drive typical social connections,” Hirsch said.

Source: Yale University

Delayed COVID Recovery could be a Protective Mechanism against Hypoxia

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COVID patients placed on ventilators can take a long time to regain consciousness. New research published the Proceedings of the National Academy of Sciences now shows that these delays may serve a purpose: protecting the brain from oxygen deprivation.

The existence of such a brain-preserving state could explain why some patients wake up days or even weeks after they stop receiving ventilation, and it suggests that physicians should take these lengthy recovery times into account when determining a patient’s prognosis.

In their study, investigators connect the pattern seen among those who have survived severe COVID with similar delays known to occur in a small fraction of cardiac arrest patients.

“The delayed recoveries in COVID patients are very much like the rare cases we’ve documented in previous research. In this new paper, we describe a mechanism to explain what we’re seeing in both types of patients,” said study co-senior author Dr Nicholas D. Schiff, a neurology professor at Weill Cornell Medicine.

He suggests that this mechanism is the brain protecting itself, pointing to animals, most notably painted turtles, that can tolerate extended periods without oxygen.

More than a decade ago, Dr Schiff and his colleagues first observed these delays among comatose cardiac arrest patients who received cooling therapy to reduce brain damage caused by a loss of blood flow. In one such case, a 71-year-old patient took 37 days to awaken, before ultimately making a near-complete recovery.

During the pandemic, Dr Schiff performed neurology consultations for COVID patients, and he soon began seeing similar, delayed awakenings occurring when patients were taken off ventilators and stopped receiving movement-limiting sedatives.

In a separate analysis of a large cohort of COVID patients from Weill Cornell Medicine and two other major U.S. medical centres, Dr Schiff and his colleagues, including co-author of the current paper, Dr Emery N. Brown, professor of anaesthesia at Harvard Medical School, found that a quarter of patients who survived ventilation took 10 days or longer to recover consciousness. The more oxygen deprivation they suffered while on the ventilator, the longer that delay.

In the prior study of cardiac patients, the researchers recorded a distinctive pattern in brain activity, one also seen in patients under deep anaesthesia. (Recordings from COVID patients are extremely limited.) Dr Schiff read that a similar pattern had been seen in the brains of painted turtles, which can withstand up to five months without oxygen under ice in the winter. To do so, they activate the same inhibitory system within the brain targeted by anaesthetics given to human cardiac and COVID patients but in novel ways developed by evolutionary specialisations.

Drs Schiff and Brown propose that, by chance, the same protective response emerges in the patients.

“It is our theory that oxygen deprivation as well as practices in the ICU, including commonly used anaesthetics, expose elements of strategies that animals use to survive in extreme conditions,” Dr Schiff said.

“These observations may offer new insights into the mechanisms of how certain anaesthetics produce unconsciousness and new approaches for ICU sedation and for fostering recovery from disorders of consciousness,” Dr Brown added.

When patients fail to regain consciousness for an extended time, physicians may recommend withdrawing life-supporting care. This threshold is typically set at 14 days or less for cardiac patients, while no such guidelines exist for COVID.

In light of this new research, however, so long as they lack brain injuries, physicians should avoid making negative projections about these patients’ potential to recover, note the researchers.

Source: Weill Cornell Medicine

Brain Changes in Autism More Widely Spread than Previously Believed

In autism, brain changes are spread throughout the cerebral cortex instead of in areas thought affect social behaviour and language, according to a new study that significantly refines scientists’ understanding of how autism spectrum disorder (ASD) progresses at the molecular level.

The study, published in Nature, represents a comprehensive effort to characterise ASD at the molecular level. While neurological disorders like Alzheimer’s disease or Parkinson’s disease have well-defined pathologies, autism and other psychiatric disorders have had a lack of defining pathology, challenging efforts to develop more effective treatments.  

The new study finds brain-wide changes in virtually all of the 11 cortical regions analysed, regardless of whether they are higher critical association regions – those involved in functions such as reasoning, language, social cognition and mental flexibility – or primary sensory regions.  

“This work represents the culmination of more than a decade of work of many lab members, which was necessary to perform such a comprehensive analysis of the autism brain,” said study author Dr Daniel Geschwind, the Gordon and Virginia MacDonald Distinguished Professor of Human Genetics, Neurology and Psychiatry at UCLA. “We now finally are beginning to get a picture of the state of the brain, at the molecular level, of the brain in individuals who had a diagnosis of autism. This defines a molecular pathology, which similar to other brain disorders such as Parkinson’s, Alzheimer’s and stroke, provides a key starting point for understanding the disorder’s mechanisms, which will inform and accelerate development of disease-altering therapies.” 
 
Just over a decade ago, Geschwind led the first effort to identify autism’s molecular pathology by focusing on two brain regions, the temporal lobe and the frontal lobe. Those regions were chosen because they are higher order association regions involved in higher cognition – especially social cognition, which is disrupted in ASD.  
 
For the new study, researchers examined gene expression in 11 cortical regions by sequencing RNA from each of the four main cortical lobes. They compared brain tissue samples obtained after death from 49 people with ASD against 54 controls individuals.  
 
While each profiled cortical region showed changes, the largest changes in RNA levels were in the visual cortex and the parietal cortex, which processes information like touch, pain and temperature. The researchers said this may reflect the sensory hypersensitivity that is frequently reported in people with ASD. Researchers found strong evidence that the genetic risk for autism is enriched in a specific group of genes expressed in neurons that has lower expression across the brain, indicating that these correlated RNA changes in the brain are likely the cause of ASD rather than a result of the disorder. 

One of the next steps is to determine whether researchers can use computational approaches to develop therapies based on reversing gene expression changes the researchers found in ASD, Geschwind said, adding that researchers can use organoids to model the changes in order to better understand their mechanisms.  

Source: University of California, Los Angeles