Category: Neurology

Categories : Cancer NeurologyTags :

Man’s Best Friend Shares Similarities in Genetics of Meningiomas

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Researchers have discovered that meningiomas – the most common type of brain tumour in humans and dogs – are extremely similar genetically. These newly discovered similarities will allow doctors to use a classification system that identifies aggressive tumours in both humans and dogs, while also opening the door for new and exciting collaborations between human and animal medicine. The researchers, from Texas A&M School of Veterinary Medicine & Biomedical Sciences (VMBS), Baylor College of Medicine and Texas Children’s Hospital, published their findings in the scientific journal Acta Neuropathologica.

Until now, the lack of reliable and viable experimental models has been a barrier to understanding the biology of and developing effective treatments for these brain tumours.

“The discovery that naturally occurring canine tumours closely resemble their human counterparts opens numerous avenues for exploring the biology of these challenging tumors,” said Dr. Akash Patel, an associate professor of neurosurgery at Baylor College of Medicine and principal investigator at the Jan and Dan Duncan Neurological Research Institute (Duncan NRI) at Texas Children’s Hospital.

“It also provides opportunities for developing and studying novel treatments applicable to both humans and dogs.”

The study was led by Patel; Dr Jonathan Levine, a VMBS professor and head of the Department of Small Animal Clinical Sciences (VSCS); and Dr Tiemo Klisch, assistant professor at Baylor College of Medicine and principal investigator at Duncan NRI. VSCS assistant professor Dr Beth Boudreau was a key collaborator.

For the project, the team analysed 62 canine meningiomas from 27 dog breeds and discovered that the tumours shared remarkable similarities to the same kinds of tumours when they occur in humans.

This is the largest study to date of the gene expression profiles of canine meningiomas.

Watching the signs

The new discovery was made possible by building on recent work conducted by Patel’s team, as well as previous work by Levine and Boudreau that explored gliomas, another type of brain tumour.

In 2019, Patel and others at Baylor College of Medicine and Texas Children’s Hospital found that they could classify meningiomas in humans into three biologically distinct subtypes – MenG A, B, and C – by analysing their RNA.

The new classification system can predict patient outcomes with greater accuracy than the standard tissue sample analysis.

“Because RNA shows how a tumour’s genes activate, it allows researchers to accurately predict how a tumour will behave – whether it will be aggressive or if it’s going to respond to certain therapies,” Levine said.

“We ended up agreeing to provide Patel with canine tumor samples we had worked years and years to archive, to see if he could isolate the RNA, which is not always easy to do,” Levine said.

“He was able to produce this very robust dataset that showed a similar pattern structure to human tumours. Our team also provided Dr Patel with key clinical outcome data, including responses to certain treatments.”

Onward to clinical trials

Now that the researchers have established a connection between tumors across the two species, they can begin preparations for clinical trials, which can take several years to plan and fund.

“We’re really interested in creating wins for both human and animal medicine,” Levine said.

“For example, we hope to give dog owners access to therapy that’s not available anywhere else in the world through clinical trials. At the same time, that information will also inform the next step of human trials.”

Incidentally, a separate group of researchers from the University of California, Davis, conducted a similar study with matching conclusions about meningiomas in dogs and people and published its work in the same journal.

The two research groups look forward to collaborating in the future to develop tumour treatments for both species.

Source: Texas A&M University

Categories : Lab Tests and Imaging NeurologyTags :

Researchers Demonstrate the Effect of Neurochemicals on fMRI Readings

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The brain is an incredibly complex and active organ that uses electricity and chemicals to transmit and receive signals between its sub-regions. Researchers have explored various technologies to directly or indirectly measure these signals to learn more about the brain. Functional magnetic resonance imaging (fMRI), for example, allows them to detect brain activity via changes related to blood flow.

Yen-Yu Ian Shih, PhD, professor of neurology and associate director of UNC’s Biomedical Research Imaging Center, and his fellow lab members have long been curious about how neurochemicals in the brain regulate and influence neural activity, blood flow, and subsequently, fMRI measurement in the brain.

A new study by the lab has confirmed their suspicions that fMRI interpretation is not as straightforward as it seems.

“Neurochemical signalling to blood vessels is less frequently considered when interpreting fMRI data,” said Shih, who also leads the Center for Animal MRI. “In our study on rodent models, we showed that neurochemicals, aside from their well-known signalling actions to typical brain cells, also signal to blood vessels, and this could have significant contributions to fMRI measurements.”

Their findings, published in Nature Communications, stem from the installation and upgrade of two 9.4-Tesla animal MRI systems and a 7-Tesla human MRI system at the Biomedical Research Imaging Center.

When activity in neurons increases in a specific brain region, blood flow and oxygen levels increase in the area, usually proportionate to the strength of neural activity. Researchers decided to use this phenomenon to their advantage and eventually developed fMRI techniques to detect these changes in the brain.

For years, this method has helped researchers better understand brain function and influenced their knowledge about human cognition and behaviour. The new study from Shih’s lab, however, demonstrates that this well-established neuro-vascular relationship does not apply across the entire brain because cell types and neurochemicals vary across brain areas.

Shih’s team focused on the striatum, a region deep in the brain involved in cognition, motivation, reward, and sensorimotor function, to identify the ways in which certain neurochemicals and cell types in the brain region may be influencing fMRI signals.

For their study, Shih’s lab controlled neural activity in rodent brains using a light-based technique, while measuring electrical, optical, chemical, and vascular signals to help interpret fMRI data. The researchers then manipulated the brain’s chemical signalling by injecting different drugs into the brain and evaluated how the drugs influenced the fMRI responses.

They found that in some cases, neural activity in the striatum went up, but the blood vessels constricted, causing negative fMRI signals. This is related to internal opioid signaling in the striatum. Conversely, when another neurochemical, dopamine, predominated signaling in striatum, the fMRI signals were positive.

“We identified several instances where fMRI signals in the striatum can look quite different from expected,” said Shih. “It’s important to be mindful of underlying neurochemical signaling that can influence blood vessels or perivascular cells in parallel, potentially overshadowing the fMRI signal changes triggered by neural activity.”

Members of Shih’s lab, including first- and co-authors Dominic Cerri, PhD, and Lindsey Walton, PhD, travelled to the University of Sussex in the United Kingdom, where they were able to perform experiments and further demonstrate the opioid’s vascular effects.

They also collected human fMRI data at UNC’s 7-Tesla MRI system and collaborated with researchers at Stanford University to explore possible findings using transcranial magnetic stimulation, a procedure that uses magnetic fields to stimulate the human brain.

By better understanding fMRI signaling, basic science researchers and physician scientists will be able to provide more precise insights into neural activity changes in healthy brains, as well as in cases of neurological and neuropsychiatric disorders.

Source: UNC School of Medicine

Categories : NeurologyTags :

ADHD Medication Associated with Reduced Mortality

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A Swedish study of more than 140 000 individuals with attention-deficit/hyperactivity disorder (ADHD) found that initiation of ADHD medication was significantly associated with a 21% lower mortality two years after diagnosis, according to results published in JAMA. This reduction was especially pronounced for unnatural-cause mortality. Females and males also saw different reductions in types of mortality.

ADHD is the most prevalent neurodevelopmental condition, affecting 5.9% of youths and 2.5% of adults worldwide, according to the 2021 World Federation of ADHD International Consensus Statement. The disorder is associated with a broad range of psychiatric and physical comorbidities, as well as adverse functional outcomes. Furthermore, individuals with ADHD are at twice the risk of premature death, mainly due to unnatural causes.

Randomised controlled trials have demonstrated that ADHD medications, including stimulant and nonstimulant medications, are effective in reducing core ADHD symptoms for children and adults with ADHS. Pharmacoepidemiological studies have also shown reduced risks of negative outcomes, including injuries, traffic collisions, and criminality, which would be expected to decrease the mortality rate. However, there are concerns regarding the cardiovascular safety of ADHD medications, especially following long-term use, which could increase the mortality rate.

To date, three studies have examined the association between ADHD medication and mortality with mixed results. These studies had significant limitations, such as the absence of a control group. To date, there has been no study on the association in adults with ADHD. There are increasing diagnoses of ADHD among adults, who have a higher prevalence of somatic comorbidities, including cardiovascular diseases and other conditions, compared with children and adolescents.

Using the Swedish national registers, the researchers investigated whether initiation of ADHD medication was associated with mortality, using the target trial emulation approach to avoid key biases in pharmacoepidemiological studies.

They assessed for all 6 medications licensed for ADHD treatment in Sweden (methylphenidate, amphetamine, dexamphetamine, lisdexamfetamine, atomoxetine, and guanfacine) during the 2007-2020 period. Analysis of the data showed that, for a two-year follow-up, lower all-cause (hazard ratio [HR], 0.79) and unnatural-cause (HR, 0.75) mortality for the ADHD medication group, but there was no significant association with natural-cause mortality (HR, 0.86). Under unnatural causes, accidental poisoning mortality was halved (HR, 0.47).

Subgroup analysis revealed that for females, the only significant reduction in mortality was for natural causes. The authors noted that this may be due to higher rates of comorbid depression, sleep disorder, atrial fibrillation, and asthma.

When follow-up was extended to five years, associations attenuated save for unnatural-cause mortality (HR, 0.89).

The authors concluded, “ADHD medication may reduce the risk of unnatural-cause mortality by alleviating the core symptoms of ADHD and its psychiatric comorbidities, leading to improved impulse control and decision-making, ultimately reducing the occurrence of fatal events, in particular among those due to accidental poisoning.”

For limitations, the observational nature of the study cannot establish causation, and the authors noted confounding effects such as nonpharmaceutical treatment of ADHD. Potential type I error resulting from multiple comparisons regarding cause-specific mortality and subgroup analyses meant the results are only exploratory. Two more limitations were uncertain adherence to medication and potential misclassification of deaths such as potential cases of suicide being marked as accidental poisoning.

Categories : Neurology PaediatricsTags :

Could a Simple Eye Reflex Test Pick up Autism in Children?

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Scientists at UC San Francisco that they may have discovered a new way to test for autism by measuring how children’s eyes move when they turn their heads. They found that children with a variant of a gene that is associated with severe autism are hypersensitive to this motion.

The gene, SCN2A, makes an ion channel that is found throughout the brain, including the region that coordinates movement – the cerebellum. Several variants of this gene are also associated with severe epilepsy and intellectual disability.

The researchers found that children with these variants have an unusual form of the reflex that stabilizes the gaze while the head is moving, called the vestibulo-ocular reflex (VOR). In children with autism, it seems to go overboard, and this can be measured with a simple eye-tracking device.

The discovery, published in the journal Neuron, could help to advance research on autism, which affects 1 out of every 36 children in the United States. And it could help to diagnose kids earlier and faster with a method that only requires them to don a helmet and sit in a chair.

“We can measure it in kids with autism who are non-verbal or can’t or don’t want to follow instructions,” said Kevin Bender, PhD, a professor in the UCSF Weill Institute for Neurosciences and co-senior author of the study. “This could be a game-changer in both the clinic and the lab.”

A telltale sign of autism in an eye reflex

Of the hundreds of gene mutations associated with autism, variants of the SCN2A gene are among the most common.

Since autism affects social communication, ion channel experts like Bender had focused on the frontal lobe of the brain, which governs language and social skills in people. But mice with an autism-associated variant of the SCN2A gene did not display marked behavioral differences associated with this brain region.

Chenyu Wang, a UCSF graduate student in Bender’s lab and first author of the study, decided to look at what the SCN2A variant was doing in the mouse cerebellum. Guy Bouvier, PhD, a cerebellum expert at UCSF and co-senior author of the paper, already had the equipment needed to test behaviors influenced by the cerebellum, like the VOR.

The VOR is easy to provoke. Shake your head and your eyes will stay roughly centered. In mice with the SCN2A variant, however, the researchers discovered that this reflex was unusually sensitive. When these mice were rotated in one direction, their eyes compensated perfectly, rotating in the opposite direction.

But this increased sensitivity came at a cost. Normally, neural circuits in the cerebellum can refine the reflex when needed, for example to enable the eyes to focus on a moving object while the head is also moving. In SCN2A mice, however, these circuits got stuck, making the reflex rigid.

A mouse result translates nearly perfectly to kids with autism

Wang and Bender had uncovered something rare: a behaviour that arose from a variant to the SCN2A gene that was easy to measure in mice. But would it work in people?

They decided to test it with an eye-tracking camera mounted on a helmet. It was a “shot in the dark,” Wang said, given that the two scientists had never conducted a study in humans.

Bender asked several families from the FamilieSCN2A Foundation, the major family advocacy group for children with SCN2A variants in the US, to participate. Five children with SCN2A autism and eleven of their neurotypical siblings volunteered.

Wang and Bender took turns rotating the children to the left and right in an office chair to the beat of a metronome. The VOR was hypersensitive in the children with autism, but not in their neurotypical siblings.

The scientists could tell which children had autism just by measuring how much their eyes moved in response to their head rotation.

A CRISPR cure in mice

The scientists also wanted to see if they could restore the normal eye reflex in the mice with a CRISPR-based technology that restored SCN2A gene expression in the cerebellum.

When they treated 30-day-old SCN2A mice – equivalent to late adolescence in humans – their VOR became less rigid but was still unusually sensitive to body motion. But when they treated 3-day-old SCN2A mice – early childhood in humans – their eye reflexes were completely normal.

“These first results, using this reflex as our proxy for autism, point to an early window for future therapies that get the developing brain back on track,” Wang said.

It’s too early to say whether such an approach might someday be used to directly treat autism. But the eye reflex test, on its own, could clear the way to more expedient autism diagnosis for kids today, saving families from long diagnostic odysseys.

“If this sort of assessment works in our hands, with kids with profound, nonverbal autism, there really is hope it could be more widely adopted,” Bender said.

Source: University of California – San Francisco

Categories : NeurologyTags :

Researchers 3D-print Functional Human Brain Tissue

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AI-generated image illustrating 3-D tissue printing

A team of scientists has developed the first 3D-printed brain tissue that can grow and function like typical brain tissue. This has important implications for scientists studying the brain and working on treatments for a broad range of neurological and neurodevelopmental disorders, such as Alzheimer’s and Parkinson’s disease.

“This could be a hugely powerful model to help us understand how brain cells and parts of the brain communicate in humans,” says Su-Chun Zhang, professor of neuroscience and neurology at UW-Madison’s Waisman Center. “It could change the way we look at stem cell biology, neuroscience, and the pathogenesis of many neurological and psychiatric disorders.”

Printing methods have limited the success of previous attempts to print brain tissue, according to Zhang and Yuanwei Yan, a scientist in Zhang’s lab. The group behind the new 3D-printing process described their method today in the journal Cell Stem Cell.

Instead of using the traditional 3D-printing approach, stacking layers vertically, the researchers went horizontally. They situated brain cells, neurons grown from induced pluripotent stem cells, in a softer “bio-ink” gel than previous attempts had employed.

“The tissue still has enough structure to hold together but it is soft enough to allow the neurons to grow into each other and start talking to each other,” Zhang says.

The cells are laid next to each other like pencils laid next to each other on a tabletop.

“Our tissue stays relatively thin and this makes it easy for the neurons to get enough oxygen and enough nutrients from the growth media,” Yan says.

The results speak for themselves – which is to say, the cells can speak to each other. The printed cells reach through the medium to form connections inside each printed layer as well as across layers, forming networks comparable to human brains. The neurons communicate, send signals, interact with each other through neurotransmitters, and even form proper networks with support cells that were added to the printed tissue.

“We printed the cerebral cortex and the striatum and what we found was quite striking,” Zhang says. “Even when we printed different cells belonging to different parts of the brain, they were still able to talk to each other in a very special and specific way.”

The printing technique offers precision – control over the types and arrangement of cells – not found in brain organoids, miniature organs used to study brains. The organoids grow with less organisation and control.

“Our lab is very special in that we are able to produce pretty much any type of neurons at any time. Then we can piece them together at almost any time and in whatever way we like,” Zhang says. “Because we can print the tissue by design, we can have a defined system to look at how our human brain network operates. We can look very specifically at how the nerve cells talk to each other under certain conditions because we can print exactly what we want.”

That specificity provides flexibility. The printed brain tissue could be used to study signaling between cells in Down syndrome, interactions between healthy tissue and neighboring tissue affected by Alzheimer’s, testing new drug candidates, or even watching the brain grow.

“In the past, we have often looked at one thing at a time, which means we often miss some critical components. Our brain operates in networks. We want to print brain tissue this way because cells do not operate by themselves. They talk to each other. This is how our brain works and it has to be studied all together like this to truly understand it,” Zhang says. “Our brain tissue could be used to study almost every major aspect of what many people at the Waisman Center are working on. It can be used to look at the molecular mechanisms underlying brain development, human development, developmental disabilities, neurodegenerative disorders, and more.”

The new printing technique should also be accessible to many labs. It does not require special bio-printing equipment or culturing methods to keep the tissue healthy, and can be studied in depth with microscopes, standard imaging techniques and electrodes already common in the field.

The researchers would like to explore the potential of specialization, though, further improving their bio-ink and refining their equipment to allow for specific orientations of cells within their printed tissue..

“Right now, our printer is a benchtop commercialised one,” Yan says. “We can make some specialised improvements to help us print specific types of brain tissue on-demand.”

Source: University of Wisconsin-Madison

Categories : NeurologyTags :

Researchers Uncover Protein that Enables Sensation of Cold

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University of Michigan researchers have identified the protein that enables mammals to sense cold, filling a long-standing knowledge gap in the field of sensory biology. The findings, published in Nature Neuroscience, could help unravel how we sense and suffer from cold temperature in the winter, and why some patients experience cold differently under particular disease conditions.

“The field started uncovering these temperature sensors over 20 years ago, with the discovery of a heat-sensing protein called TRPV1,” said neuroscientist Shawn Xu, a professor at the U-M Life Sciences Institute and a senior author of the new research.

“Various studies have found the proteins that sense hot, warm, even cool temperatures – but we’ve been unable to confirm what senses temperatures below about 60 degrees Fahrenheit (15.5°C).”

In a 2019 study, researchers in Xu’s lab discovered the first cold-sensing receptor protein in Caenorhabditis elegans, a species of millimetre-long worms that the lab studies as a model system for understanding sensory responses.

Because the gene that encodes the C. elegans protein is evolutionarily conserved across many species, including mice and humans, that finding provided a starting point for verifying the cold sensor in mammals: a protein called GluK2 (short for Glutamate ionotropic receptor kainate type subunit 2).

For this latest study, a team of researchers from the Life Sciences Institute and the U-M College of Literature, Science, and the Arts tested their hypothesis in mice that were missing the GluK2 gene, and thus could not produce any GluK2 proteins. Through a series of experiments to test the animals’ behavioural reactions to temperature and other mechanical stimuli, the team found that the mice responded normally to hot, warm and cool temperatures, but showed no response to noxious cold.

GluK2 is primarily found on neurons in the brain, where it receives chemical signals to facilitate communication between neurons. But it is also expressed in sensory neurons in the peripheral nervous system.

“We now know that this protein serves a totally different function in the peripheral nervous system, processing temperature cues instead of chemical signals to sense cold,” said Bo Duan, U-M associate professor of molecular, cellular, and developmental biology and co-senior author of the study.

While GluK2 is best known for its role in the brain, Xu speculates that this temperature-sensing role may have been one of the protein’s original purposes. The GluK2 gene has relatives across the evolutionary tree, going all the way back to single-cell bacteria.

“A bacterium has no brain, so why would it evolve a way to receive chemical signals from other neurons? But it would have great need to sense its environment, and perhaps both temperature and chemicals,” said Xu, who is also a professor of molecular and integrative physiology at the U-M Medical School. “So I think temperature sensing may be an ancient function, at least for some of these glutamate receptors, that was eventually co-opted as organisms evolved more complex nervous systems.”

In addition to filling a gap in the temperature-sensing puzzle, Xu believes the new finding could have implications for human health and well-being. Cancer patients receiving chemotherapy, for example, often experience painful reactions to cold.

“This discovery of GluK2 as a cold sensor in mammals opens new paths to better understand why humans experience painful reactions to cold, and even perhaps offers a potential therapeutic target for treating that pain in patients whose cold sensation is overstimulated,” Xu said.

Source: University of Michigan

Categories : Neurology Pain ManagementTags :

Astronauts’ ‘Space Headaches’ may Yield Insights into Those Suffered on Earth

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Space travel and zero gravity can take a toll on the body. A new study has found that astronauts with no prior history of headaches may experience migraine and tension-type headaches during long-haul space flight, which includes more than 10 days in space. Studying this type of headache may provide new insights into the mechanisms behind headaches on Earth. The study was published in Neurology.

“Changes in gravity caused by space flight affect the function of many parts of the body, including the brain,” said study author W. P. J. van Oosterhout, MD, PhD, of Leiden University Medical Center in the Netherlands.

“The vestibular system, which affects balance and posture, has to adapt to the conflict between the signals it is expecting to receive and the actual signals it receives in the absence of normal gravity. This can lead to space motion sickness in the first week, of which headache is the most frequently reported symptom. Our study shows that headaches also occur later in space flight and could be related to an increase in pressure within the skull.”

The study involved 24 astronauts from the European Space Agency, the U.S. National Aeronautics and Space Administration (NASA) and the Japan Aerospace Exploration Agency. They were assigned to International Space Station expeditions for up to 26 weeks from November 2011 to June 2018.

Prior to the study, nine astronauts reported never having any headaches and three had a headache that interfered with daily activities in the last year.

None of them had a history of recurrent headaches or had ever been diagnosed with migraine.

Of the total participants, 22 astronauts experienced one or more episode of headache during a total of 3596 days in space for all participants. Astronauts completed health screenings and a questionnaire about their headache history before the flight.

During space flight, astronauts filled out a daily questionnaire for the first seven days and a weekly questionnaire each following week throughout their stay in the space station.

The astronauts reported 378 headaches in flight. Researchers found that 92% of astronauts experienced headaches during flight compared to just 38% of them experiencing headaches prior to flight.

Of the total headaches, 170, or 90%, were tension-type headache and 19, or 10%, were migraine. Researchers also found that headaches were of a higher intensity and more likely to be migraine-like during the first week of space flight.

During this time, 21 astronauts had one or more headaches for a total of 51 headaches – of which 39 were considered tension-type headaches and 12 were migraine-like or probable migraine.

In the three months after return to Earth, none of the astronauts reported any headaches.

“Further research is needed to unravel the underlying causes of space headache and explore how such discoveries may provide insights into headaches occurring on Earth,” said Van Oosterhout.

“Also, more effective therapies need to be developed to combat space headaches as for many astronauts this a major problem during space flights.”

This research does not prove that going into space causes headaches; it only shows an association.

A limitation of the study was that astronauts reported their own symptoms, so they may not have remembered all the information accurately.

Source: American Academy of Neurology

Categories : Neurology Substance UseTags :

Continued Cocaine Use Disrupts Communication between Major Brain Networks

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A collaborative research endeavour by scientists in the Departments of Radiology, Neurology, and Psychology and Neuroscience at the UNC School of Medicine have demonstrated the deleterious effects of chronic cocaine use on the functional networks in the brain.

Their study titled “Network Connectivity Changes Following Long-Term Cocaine Use and Abstinence,” was highlighted by the editor of Journal of Neuroscience in “This Week in The Journal.” The findings show that continued cocaine use affects how crucial neural networks communicate with one another in the brain, including the default mode network (DMN), the salience network (SN), and the lateral cortical network (LCN).

“The disrupted communication between the DMN and SN can make it harder to focus, control impulses, or feel motivated without the drug,” said Li-Ming Hsu, PhD, assistant professor of radiology and lead author on the study. “Essentially, these changes can impact how well they respond to everyday situations, making recovery and resisting cravings more challenging.”

Hsu led this project during his postdoctoral tenure at the Center for Animal MRI in the Biomedical Research Imaging Center and the Department of Neurology. The work provides new insights into the brain processes that underlie cocaine addiction and creates opportunities for the development of therapeutic approaches and the identification of an imaging marker for cocaine use disorders.

The brain operates like an orchestra, where each instrumentalist has a special role crucial for creating a coherent piece of music. Specific parts of the brain need to work together to complete a task. The DMN is active during daydreams and reflections, the SN is crucial for attentiveness, and the CEN, much like a musical conductor, plays a role in our decision-making and problem-solving.

The research was motivated by observations from human functional brain imaging studies suggesting chronic cocaine use alters connectivity within and between the major brain networks. Researchers needed a longitudinal animal model to understand the relationship between brain connectivity and the development of cocaine dependence, as well as changes during abstinence.

Researchers employed a rat model to mimic human addiction patterns, allowing the models to self-dose by nose poke. Paired with advanced neuroimaging techniques, the behavioural approach enables a deeper understanding of the brain’s adaptation to prolonged drug use and highlights how addictive substances can alter the functioning of critical brain networks.

Hsu’s research team used functional MRI scans to explore the changes in brain network dynamics on models that self-administrated cocaine. Over a period of 10 days followed by abstinence, researchers observed significant alterations in network communication, particularly between the DMN and SN.

These changes were more pronounced with increased cocaine intake over the 10 days of self-administration, suggesting a potential target for reducing cocaine cravings and aiding those in recovery. The changes in these networks’ communication could also serve as useful imaging biomarkers for cocaine addiction.

The study also offered novel insights into the anterior insular cortex (AI) and retrosplenial cortex (RSC). The former is responsible for emotional and social processing; whereas, the latter controls episodic memory, navigation, and imagining future events. Researchers noted that there was a difference in coactivity between these two regions before and after cocaine intake. This circuit could be a potential target for modulating associated behavioural changes in cocaine use disorders.

“Prior studies have demonstrated functional connectivity changes with cocaine exposure; however, the detailed longitudinal analysis of specific brain network changes, especially between the anterior insular cortex (AI) and retrosplenial cortex (RSC), before and after cocaine self-administration, and following extended abstinence, provides new insights,” said Hsu.

Source: University of North Carolina Health Care

Categories : Neurology OphthalmologyTags :

In the Fight against Brain Pathogens, the Eyes Have it

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The eyes have been called the window to the brain. It turns out they also serve as an immunological barrier that protects the organ from pathogens and even tumours, Yale researchers have found. In a new study, researchers showed that vaccines injected into the eyes of mice can help disable the herpes virus, a major cause of brain encephalitis.

To their surprise, the vaccine activates an immune response through lymphatic vessels along the optic nerve.

The results were published Feb. 28 in the journal Nature.

“There is a shared immune response between the brain and the eye,” said Eric Song, an associate research scientist and resident physician in Yale School of Medicine’s Department of Immunobiology and corresponding author of the paper.

“And the eyes provide easier access for drug therapies than the brain does.”

Wanting to explore immunological interactions between brain and eyes, the research team, which was led by Song, found that the eyes have two distinct lymphatic systems regulating immune responses in the front and rear of the eye.

After they vaccinated mice with inactivated herpes virus, the researchers found that lymphatic vessels in the optic nerve sheath at the rear of the eye protected mice not only from active herpes infections, but from bacteria and even brain tumors.

Harnessing this new biology, Song’s team is currently testing newly created drugs from his lab delivered through eye injections that may help combat macular edema, or leaky blood vessels of the retina common in people with diabetes, and glaucoma.

“These results reveal a shared lymphatic circuit able to mount a unified immune response between posterior eye and the brain, highlighting an understudied immunological feature of the eyes and opening up the potential for new therapeutic strategies in ocular and central nervous system diseases,” the authors wrote.

Source: Yale University

Categories : NeurologyTags :

During Sleep, Brain Waves Flush out Metabolic Waste

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The rhythmic waves of electric pulses produced by neurons during sleep have long fascinated science and defied explanation. Slow brain waves are associated with restful, refreshing sleep. Now, scientists have found that brain waves help flush waste out of the brain during sleep. Individual nerve cells coordinate to produce rhythmic waves that propel fluid through dense brain tissue, washing the tissue in the process. This finding could help lead to new ways to treat diseases such as Alzheimer’s.

“These neurons are miniature pumps. Synchronised neural activity powers fluid flow and removal of debris from the brain,” explained first author Li-Feng Jiang-Xie, PhD, a postdoctoral research associate in the Department of Pathology & Immunology. “If we can build on this process, there is the possibility of delaying or even preventing neurological diseases, including Alzheimer’s and Parkinson’s disease, in which excess waste – such as metabolic waste and junk proteins – accumulate in the brain and lead to neurodegeneration.”

The Washington University School of Medicine in St. Louis researchers published their findings in Nature.

In carrying out the energy-demanding tasks of the brain’s functions, brain cells consume nutrients and create metabolic waste, which must be disposed of.

“It is critical that the brain disposes of metabolic waste that can build up and contribute to neurodegenerative diseases,” said Jonathan Kipnis, PhD, the Alan A. and Edith L. Wolff Distinguished Professor of Pathology & Immunology and a BJC Investigator. Kipnis is the senior author on the paper. “We knew that sleep is a time when the brain initiates a cleaning process to flush out waste and toxins it accumulates during wakefulness. But we didn’t know how that happens. These findings might be able to point us toward strategies and potential therapies to speed up the removal of damaging waste and to remove it before it can lead to dire consequences.”

But the dense brain makes cleaning difficult. Cerebrospinal fluid surrounding the brain enters and weaves through intricate cellular webs, collecting toxic waste as it travels. Upon exiting the brain, contaminated fluid must pass through a barrier before spilling into the lymphatic vessels in the dura mater, which envelopes the brain. But what powers the movement of fluid into, through and out of the brain?

Studying the brains of sleeping mice, the researchers found that neurons drive cleaning efforts by firing electrical signals in a coordinated fashion to generate rhythmic waves in the brain, Jiang-Xie explained. They determined that such waves propel the fluid movement.

The research team silenced specific brain regions so that neurons in those regions didn’t create rhythmic waves. Without these waves, fresh cerebrospinal fluid could not flow through the silenced brain regions and trapped waste couldn’t leave the brain tissue.

“One of the reasons that we sleep is to cleanse the brain,” Kipnis said. “And if we can enhance this cleansing process, perhaps it’s possible to sleep less and remain healthy. Not everyone has the benefit of eight hours of sleep each night, and loss of sleep has an impact on health. Other studies have shown that mice that are genetically wired to sleep less have healthy brains. Could it be because they clean waste from their brains more efficiently? Could we help people living with insomnia by enhancing their brain’s cleaning abilities so they can get by on less sleep?”

Brain wave patterns change throughout sleep cycles. Of note, taller brain waves with larger amplitude move fluid with more force. The researchers are now interested in understanding why neurons fire waves with varying rhythmicity during sleep and which regions of the brain are most vulnerable to waste accumulation.

“We think the brain-cleaning process is similar to washing dishes,” neurobiologist Jiang-Xie explained. “You start, for example, with a large, slow, rhythmic wiping motion to clean soluble wastes splattered across the plate. Then you decrease the range of the motion and increase the speed of these movements to remove particularly sticky food waste on the plate. Despite the varying amplitude and rhythm of your hand movements, the overarching objective remains consistent: to remove different types of waste from dishes. Maybe the brain adjusts its cleaning method depending on the type and amount of waste.”

Source: Washington University School of Medicine