Category: Neurology

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MRI Unveils Secrets of Brains under Anaesthesia

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A study published in eLife reveals how the brains of humans and other primates under anaesthesia differ from mammals such as mice, with the visual cortex in primates being isolated from certain effects.

Anaesthesia still holds mysteries for modern science. Electroencephalography (EEG) studies show that, during anaesthesia, the brain is put into a deep sleep-like state in which periods of rhythmic electrical activity alternate with periods of complete inactivity. This state is called burst-suppression. Until now, it was unclear where exactly this state happens in the brain and which brain areas are involved.

Shedding light on the phenomenon would help better understand how the brain functions under anaesthesia. To this end, researchers used functional magnetic resonance imaging (fMRI) to study the precise spatial distribution of synchronously working brain regions in anaesthetised humans, long-tailed macaques, common marmosets and rats. They were able to show for the first time that the areas where burst-suppression is evident differ significantly in primates and rodents. While in rats large parts of the cerebral cortex synchronously show the burst-suppression pattern, in primates individual sensory regions, such as the visual cortex, are excluded from it.

“Our brain can be thought of as a full soccer stadium when we are awake,” explained Nikoloz Sirmpilatze, lead author of the study. “Our active neurons are like tens of thousands of spectators all talking at once. Under anaesthesia, however, neuronal activity is synchronised. You can measure this activity using EEG as uniform waves, as if all the spectators in the stadium were singing the same song. In deep anaesthesia, this song is repeatedly interrupted by periods of silence. This is called burst-suppression. The deeper the anaesthesia, the shorter the phases of uniform activity, the bursts, and the longer the periodically recurring inactive phases, the so-called suppressions.”

The phenomenon is caused by many different anaesthetics, some of which vary in their mechanisms of action. And burst-suppression is also detectable in coma patients. However, it is not known whether this condition is a protective reaction of the brain or a sign of impaired functioning. It has also been unclear where in the brain burst-suppression occurs and which brain areas are involved, as localisation by EEG alone is not possible.

To answer this question, the researchers fMRI. In the first part of the study, the researchers established a system to evaluate fMRI data in humans, monkeys and rodents in a standardised manner using the same method. To do this, they used simultaneously-measured EEG and fMRI data from anaesthetised patients that had been generated in a previous study. “We first looked to see whether the burst-suppression detected in the EEG was also visible in the fMRI data and whether it showed a certain pattern,” says Nikoloz Sirmpilatze. “Based on that, we developed a new algorithm that allowed detecting burst-suppression events in the experimental animals using fMRI, without additional EEG measurement.”

The researchers then performed fMRI measurements in anaesthetised long-tailed macaques, common marmosets and rats. In all animals, they were able to detect and precisely localise burst-suppression as a function of anesthetic concentration. The spatial distribution of burst-suppression showed that in both humans and monkey species, certain sensory areas, such as the visual cortex, were excluded from it. In contrast, in the rats, the entire cerebral cortex was affected by burst-suppression.

“At the moment, we can only speculate about the reasons,” said Nikoloz Sirmpilatze, who was awarded the German Primate Center’s 2021 PhD Thesis Award for his work. “Primates orient themselves mainly through their sense of sight. Therefore, the visual cortex is a highly specialised region that differs from other brain areas by special cell types and structures. In rats, this is not the case. In future studies, we will investigate what exactly happens in these regions during anaesthesia to ultimately understand why burst-suppression is not detectable there with fMRI.”

Susann Boretius, senior author of the study adds: “The study not only raises the question of the extent to which rodents are suitable models for many areas of human brain research, especially when it comes to anaesthesia, but the results also have many implications for neuroscience and the evolution of neural networks in general.”

Source: Deutsches Primatenzentrum (DPZ)/German Primate Center

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An Anti-HIV Drug for Memory Recall in Older Adults?

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The human brain usually stores memories in groups so that the recollection of one significant memory triggers the recall of others connected by time. With ageing, the brain gradually loses this ability to link related memories.

Now, researchers have discovered a key molecular mechanism behind this memory linking, and also identified a way to restore this brain function in middle-aged mice. They also found an anti-HIV drug that can do this.

Published in Nature, the findings suggest a new method for strengthening human memory in middle age and a possible early intervention for dementia.

“Our memories are a huge part of who we are,” explained Professor Alcino Silva. “The ability to link related experiences teaches how to stay safe and operate successfully in the world.”

The team from UCLA focused on a gene called CCR5 that encodes the CCR5 receptor – the same one that HIV hitches a ride on to infect brain cells, resulting in memory loss in AIDS patients.

In previous work, Prof Silva’s lab showed that CCR5 expression reduced memory recall.

In the current study, Prof Silva and his colleagues discovered a central mechanism underlying mice’s ability to link their memories of two different cages. Using a tiny microscope, the researchers observed neurons firing and creating new memories in the brains of the mice.

They found that boosting CCR5 gene expression in the brains of middle-aged mice interfered with memory linking, with animals forgetting the connection between the two cages.

Mice with the CCR5 gene knocked out were able to link memories that normal mice could not.

Proof Silva had previously studied the anti-HIV drug maraviroc, which inhibits the entry of HIV into human cells. His lab discovered that maraviroc also suppressed CCR5 in the brains of mice.

“When we gave maraviroc to older mice, the drug duplicated the effect of genetically deleting CCR5 from their DNA,” said Prof Silva. “The older animals were able to link memories again.”

The finding suggests that maraviroc could be used off-label to help restore middle-aged memory loss, as well as reverse the cognitive deficits caused by HIV infection.

“Our next step will be to organise a clinical trial to test maraviroc’s influence on early memory loss with the goal of early intervention,” said Prof Silva. “Once we fully understand how memory declines, we possess the potential to slow down the process.”

All of this raises a question: what’s the purpose of a gene that interferes with the brain’s ability to link memories?

“Life would be impossible if we remembered everything,” said Prof Silva. “We suspect that CCR5 enables the brain to connect meaningful experiences by filtering out less significant details.”

Source: University of California – Los Angeles Health Sciences

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Scientists Discover a Difference in Brains of Psychopathic Individuals

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Neuroscientists report in the Journal of Psychiatric Research that they have discovered a biological difference between psychopaths and non-psychopaths.

Using magnetic resonance imaging (MRI) scans, they found that a region of the forebrain known as the striatum was on average 10% larger in psychopathic individuals compared to a control group of individuals with low or no psychopathic traits.

Psychopaths, or those with psychopathic traits, are generally defined as individuals that have an egocentric and antisocial personality. It is a neuropsychiatric disorder marked by deficient emotional responses, lack of empathy, and poor behavioural controls, commonly resulting in persistent antisocial deviance and criminal behaviour. Accumulating research suggests that psychopathy follows a developmental trajectory with strong genetic influences, and which precipitates deleterious effects on widespread functional networks, particularly within paralimbic regions of the brain.

The striatum, which is a part of the forebrain, the subcortical region of the brain that contains the entire cerebrum, coordinates multiple aspects of cognition, including both motor and action planning, decision-making, motivation, reinforcement, and reward perception.

Previous studies had indicated an overly active striatum in psychopaths but had not conclusively determined the impact of its size on behaviours. The new study reveals a significant biological difference between people who have psychopathic traits and those who do not.

A better understanding of the role of biology in antisocial and criminal behaviour may help improve existing theories of behaviour, as well as inform policy and treatment.

Source: Nanyang Technical University

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How the Brain Blocks out Unwanted Memories

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In order to prevent the mind becoming flooded with unwanted memories, a brain region determines when a person is about to think of an unwanted memory and then signals other regions to suppress it. The discovery was recently published in JNeurosci.

Preventing unwanted memories from coming to mind is an adaptive ability of humans. This ability relies on inhibitory control processes in the prefrontal cortex to modulate hippocampal retrieval processes. How and when reminders to unwelcome memories come to trigger prefrontal control mechanisms remains unknown.

Crespo García et al. measured participants’ brain activity with both EEG and fMRI while they completed a memory task. The participants memorised sets of words (ie, gate and train) and were asked to either recall a cue word’s pair (see gate, think about train) or only focus on the cue word (see gate, only think about gate). During proactive memory suppression, activity increased in the anterior cingulate cortex (ACC), a brain region involved in cognitive control, within the first 500 milliseconds of the task. The ACC relayed information to the dorsolateral prefrontal cortex (DLPFC), which then inhibited activity in the hippocampus, a key region for memory recall. The activity levels in the ACC and DLPFC remained low for the rest of the trial, a sign of success — the memory was stopped early enough so no more suppression was needed. If the memory was not suppressed in time, the ACC generated a reactive alarm, increasing its activity to signal to the DLPFC to stop the intrusion.

Source: EurekAlert!

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People with Epilepsy Live Significantly Shorter Lives

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A Danish cohort study published in Brain shows that people with epilepsy live 10-12 years fewer than those without the condition, with a slightly greater reduction for men than women. The study researchers also found that excess mortality is particularly pronounced among people with epilepsy and mental disorders.

One of the most frequently occurring neurological diseases, epilepsy affects 50 million people worldwide, and is known to increase the risk of early death by three times.

“The significantly reduced life expectancy is found both in people who develop epilepsy as a result of an underlying condition, such as brain cancer or stroke, and in those who develop epilepsy without an obvious underlying cause,” explained Julie Werenberg Dreier, one of the researchers behind the study.

The average reduction in life expectancy was 12 years for men with epilepsy and 11 years for women. Among people with epilepsy and mental disorders life expectancy was on average reduced by up to 16 years.

“We discovered that the reduced life expectancy for people with epilepsy was related to a wide range of causes of death which don’t just include the neurological, but also cardiovascular diseases, psychiatric disorders, alcohol related conditions, accidents and suicide,” said Jakob Christensen, one of the researchers behind the study.

Researchers used Danish healthcare register to follow almost six million Danes, including more than 130 000 people with epilepsy.

“The large study has enabled detailed analyses of a range of different causes of death and, for the first time, we’ve been able to estimate the number of years lost due to individual causes of death in people with epilepsy. This is important information as it can be used to target preventive efforts in order to reduce the mortality gap that we currently see in people with epilepsy,” said Julie Werenberg Dreier.

The mortality rate among people with epilepsy is due to a wide range of different conditions that cut across virtually all medical specialities, the researchers said. There is therefore a need for a collective effort to reduce mortality.

“The alarming results provide important knowledge for all healthcare professionals who, in one way or another, come into contact with people with epilepsy — also when prioritising and allocating resources in the healthcare system. The results clearly show how serious a disease epilepsy can be, and the findings of the study should be used in the prioritisation and planning of preventive measures,” said Jakob Christensen, emphasising that the results confirm the tendencies that have been shown in a few smaller studies which have estimated reduction in life expectancy in people with epilepsy.

“The study should be followed up by additional research, for example into the questions of how medical treatment and recurring seizures affect life expectancy.”

Source: Aarhus University

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Scientists Discover the Neurological Basis of Food Cravings in Pregnancy

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By examining mice, which get pregnancy cravings similar to humans, scientists have identified the neurological basis of food craving during pregnancy.

During pregnancy, the mother’s body undergoes a series of physiological and behavioural changes to create an environment facilitating the embryo’s development. Frequent consumption of tasty, high calorie foods driven by the cravings contributes to weight gain and obesity in pregnancy, with possible negative consequences for the baby’s health.

“There are many myths and popular beliefs regarding these cravings, although the neuronal mechanisms that cause them are not widely known,” noted study leader March Claret, at the University of Barcelona and leader of the study published in the journal Nature Metabolism.

The researchers found that the brains of pregnant female mice undergoes changes in the functional connections of the brain reward circuits, as well as the taste and sensorimotor centres. Mice, like pregnant women, are also more sensitive to sweet food, and develop binge-eating behaviours towards high calorie foods. “The alteration of these structures made us explore the mesolimbic pathway, one of the signal transmission pathways of dopaminergic neurons. Dopamine is a key neurotransmitter in motivational behaviours,” notes Claret, member of the Department of Medicine of the UB and the Diabetes and Associated Metabolic Diseases Networking Biomedical Research Centre (CIBERDEM).

The team saw that dopamine levels and dopamine receptor (D2R) activity increased in the nucleus accumbens, a brain region involved in the reward circuit. “This finding suggests that the pregnancy induces a full reorganisation of the mesolimbic neural circuits through the D2R neurons,” noted study leader Roberta Haddad-Tóvolli. “These neuronal cells – and their alteration – would be responsible for the cravings, since food anxiety, typical during pregnancy, disappeared after blocking their activity.”

The team demonstrated that persistent cravings have consequences for the offspring, affecting the metabolism and development of neural circuits that regulate food intake, leading to weight gain, anxiety and eating disorders. “These results are shocking, since many of the studies are focused on the analysis of how the mother’s permanent habits – such as obesity, malnutrition, or chronic stress – affect the health of the baby. However, this study indicates that short but recurrent behaviours, such as cravings, are enough to increase the psychological and metabolic vulnerability of the offspring,” concluded Claret.

The conclusions of the study could contribute to the improvement of nutritional guidelines for pregnant women in order to ensure a proper prenatal nutrition and prevent the development of diseases.

Source: University of Barcelona

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Mental Processing of Autistic and Non-autistic People is Similar

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Findings published in Journal of Psychopathology and Clinical Science reveal there are fundamental similarities between autistic and non-autistic people in mental processing. The study findings were made available online ahead of ahead of World Autism Day on the 2nd of April.

The brain uses two systems to process information: System 1 for quicker intuitive judgements, and System 2 for slower rational thinking. In autistic people, these systems are thought to work differently ad underlie difficulties they may have in daily life and the workplace.

Yet, this landmark study reports that these fundamental psychological systems are not impaired in autistic people as once thought. The study, involving more than 1000 people, tested the link between autism and ‘quick’ intuitive and ‘slow’ rational thinking.

In three experiments, they analysed the link between autistic personality traits and thinking style. In the fourth, they compared 200 autistic and over 200 non-autistic people. Overall, their results showed that autistic people think as quickly and as rationally as non-autistic people.

Based on these findings, the researchers conclude that certain, fundamental mental processes are more similar between autistic and non-autistic people than prior belief. In light of these findings, they call for a shift in the way that society thinks about autism as a mental processing disorder.

They also recommend that it might be important to redesign educational, clinical, and workplace support for autistic people and their families. Support should be much more targeted, instead of assuming that autistic people all have mental processing difficulties, they say.

The research team argue that the requirement to make ‘reasonable adjustments’ such as allowing extra time in exams and extending deadlines, is not an evidence-based way to support neurodivergent people.

Instead, more fundamental changes could be necessary – for example, changing social and sensory environments, making them more equitable autistic people.

Source: University of Bath

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The Claustrum: A Mysterious Brain Region Involved with Pain

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A new review paper, published in the journal Brain, has shown that a mysterious brain region called the claustrum may play an important role in the experience of pain. This densely interconnected, but difficult to access area of the brain may be the next frontier in improving outcomes for brain damage patients.

The claustrum is a brain region that has been investigated for over 200 years, yet its precise function remains unknown. A 2005 article suggested it to be critically linked to consciousness, which spurred a renewed interest in this region, with recent research revealing its high level of interconnectedness.

Credit: Oxford University

Oxford University researchers reviewed studies of patients with rare cases of lesions in the claustrum, which show cognitive impairments and seizures. There may be many more cases to be uncovered due to the lack of clinical focus on the claustrum.

They also uncovered an underappreciated link between the claustrum and pain. It is already known that there are links between the claustrum and perception, salience and the sleep-wake cycle, but this is the first time a research team has shown how the claustrum might be more involved in the debilitating experience of pain.

Dr. Adam Packer, the lead author of the study, says that “The problem with understanding how the claustrum works is that it is deep inside the brain, and damage that is specific to it is a very rare occurrence. What makes it more difficult to work out what the claustrum actually does is that these rare occurrences are also linked to such a broad range of symptoms.”

“Clearly, when the claustrum is damaged the effects are severe and better therapies are urgently needed. It is possible that claustrum damage is more common than we currently realise, and it may be a crucial component in many more brain damage cases.”

“This work is important because it gives us some insight into the cognitive and neurological processes in which the claustrum may be involved, and gives us targets to pursue in basic research in the lab.”

The researchers found several recorded instances of either infection, autoimmune, or other process that attacked the claustrum in particular, and by analysing the results of these studies and others the most common symptoms in patients were cognitive impairment and seizures.

Additional research is needed for a better understanding of the claustrum and the impact of damage to the claustrum, which could eventually change clinical guidelines.

Source: University of Oxford

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Amygdala Enlargement in Kids with ASD Starts Early

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The amygdala, which is enlarged in two-year-old children with autism spectrum disorder (ASD), begins its accelerated growth between 6 and 12 months of age, suggests a study appearing in the American Journal of Psychiatry. The findings indicate that therapies to reduce the symptoms of ASD might have the greatest chance of success if they begin in the first year of life, before the amygdala begins its accelerated growth.

The amygdala, which is involved in processing emotions, such as interpreting facial expression in typically developing children increases substantially in volume from 7.5 to 18.5 years of age. The amygdala in children with autism is initially larger, but does not undergo the age-related increase observed in typically developing children.

The study included 408 infants, 270 of whom with an increased ASD risk from having an older sibling with ASD, 109 typically developing infants, and 29 infants with Fragile X syndrome. The researchers conducted MRI scans of the children at 6, 12 and 24 months of age. They found that the 58 infants who went on to develop ASD had a normal-sized amygdala at 6 months, but an enlarged amygdala at 12 months and 24 months. Moreover, the faster the rate of amygdala overgrowth, the greater the severity of ASD symptoms at 24 months. The infants with Fragile X syndrome had no differences in amygdala growth but enlargement of the caudate, which was linked to increased repetitive behaviours.

The researchers suggested that difficulty in processing sensory information during infancy may stress the amygdala, leading to its overgrowth.

Source: NIH

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Experiments to Test Consciousness All Fall Short

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A study examining various experiments each designed to prove one of four conflicting theories of consciousness has discovered that they are all flawed: predetermined to prove the theory they are designed to test. The surprising conclusion is that the nature of the experiment largely determines its result.

In neuroscience, there are currently four leading theories trying to explain how the experience of consciousness emerges from neural activity. In this unique study, researchers re-examined hundreds of experiments that support contradictory theories.

The study, published in Nature Human Behaviour, shows that the inconsistencies in the experiments’ findings are mainly due to methodological differences or the methodological choices made by the researchers, predetermines their results.

Employing artificial intelligence, researchers re-examined 412 experiments, and found that scientists’ methodological choices actually determined the result of the experiment – so much so that an algorithm could predict which theory they were designed to support with 80% success.

Professor Liad Mudrik led the study. He explained: “The big question is how consciousness is born out of activity in the brain, or what distinguishes between conscious processing and unconscious processing,” Prof Mudrik explained. “For example, if I see a red rose, my visual system processes the information and reports that there is a red stimulus in front of me. But what allows me – unlike a computer for example – to experience this colour? To know how it feels? In recent years, a number of neuroscientific theories have been proposed to explain how conscious experience arises from neural activity. And although the theories provide utterly different explanations, each of them was able to gather empirical evidence to justify itself, based on multiple experiments that were conducted. We re-examined all these experiments, and showed that the parameters of the experiment actually determine its results. The artificial intelligence we used knew how to predict with an 80% success rate which theory the experiment would support, based solely on the researchers’ methodological choices.”

The study of consciousness has four leading theories, with contradicting predictions about the neural underpinnings of conscious experience. The Global Neuronal Workspace Theory maintains that there is a central neural network, and when information enters it, it is being broadcasted throughout the brain, becoming conscious. The Higher Order Thought Theory claims that there is a higher order neural state that ‘points’ at activity in lower-level areas, marking this content as conscious. A third theory, called Recurrent Processing Theory, claims that information that is reprocessed within the sensory areas themselves, in the form of recurrent processing, becomes conscious. And finally, a fourth theory – Integrated Information Theory – defines consciousness as integrated information in the brain, claiming that the posterior regions are the physical substrates of consciousness.

“Each of these theories offers convincing experiments to support them, so the field is polarized, with no agreed-upon neuroscientific account of consciousness,” said Prof Mudrik.

In-depth analysis of all of the 412 experiments designed to test the four leading theories showed that they were constructed differently. For example, some experiments focused on different states of consciousness, such as a coma or a dream, and others studied changes in the content of consciousness of healthy subjects. Some experiments tested connectivity metrics were tested, and others did not. “Researchers make a series of decisions as they build their experiment, and we demonstrated that these decisions alone – without even knowing the results of the experiments – already predict which theory these experiments will support. That is, these theories were tested in different manners, though they try to explain the same phenomenon,” Prof Mudrik said.

“Another one of our findings was that the vast majority of the experiments we analysed supported the theories, rather than challenging them. There appears to be a built-in confirmation bias in our scientific praxis, though the philosopher of science Karl Popper said that science advances by refuting theories, not by confirming them,” added Prof. Mudrik. “Moreover, when you put together all of the findings that were reported in these experiments, it seems like almost the entire brain is involved in creating the conscious experience, which is not consistent with any of the theories. In other words, it would appear that the real picture is larger and more complex than any of the existing theories suggest. It would seem that none of them is consistent with the data, when aggregated across studies, and that the truth lies somewhere in the middle.”

Source: EurekAlert!