Category: Neurology

Categories : Neurology Regenerative MedicineTags :

New Regeneration Drug for Spinal Cord Injury Passes Safety Check

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Researchers in the UK have evaluated a potential drug for the treatment of spinal cord injury (SCI), which could potentially regrow damaged nerves, and found it to be safe and tolerable. The results of their Phase 1 clinical trial were published in British Journal of Clinical Pharmacology and evaluated the KCL-286 drug, which activates retinoic acid receptor beta (RARb) in the spine to promote recovery.

There are no licensed drugs that can fix the adult central nervous system’s inability to regenerate. Implants have been able to restore some function, but for most, spinal cord injuries are life-changing.

Previous studies have shown that nerve growth can be stimulated by activating the RARb2 receptor, but no drug suitable for humans has been developed. KCL-286, an RARb2 agonist, was developed by Professor Corcoran and team and used in a first in man study to test its safety in humans.

The study by the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London, recruited 109 healthy males in a single ascending dose (SAD) adaptive design with a food interaction (FI) arm, and multiple ascending dose (MAD) arm. Participants in each arm were further divided into different dose treatments.

SAD studies are designed to establish the safe dosage range of a medicine by providing participants with small doses before gradually increasing the dose provided. Researchers look for any side effects, and measure how the medicine is processed within the body. MAD studies explore how the body interacts with repeated administration of the drug, and investigate the potential for a drug to accumulate within the body.

Researchers found that participants were able to safely take 100mg doses of KCL-286, with no severe adverse events.

Professor Jonathan Corcoran, Professor of Neuroscience and Director of the Neuroscience Drug Discovery Unit, at King’s IoPPN and the study’s senior author said, “This represents an important first step in demonstrating the viability of KCL-286 in treating spinal cord injuries. This first-in-human study has shown that a 100mg dose delivered via a pill can be safely taken by humans. Furthermore, we have also shown evidence that it engages with the correct receptor.

“Our focus can hopefully now turn to researching the effects of this intervention in people with spinal cord injuries.”

Dr Bia Goncalves, a senior scientist and project manager of the study, and the study’s first author from King’s IoPPN said, “Spinal Cord Injuries are a life changing condition that can have a huge impact on a person’s ability to carry out the most basic of tasks, and the knock-on effects on their physical and mental health are significant.

“The outcomes of this study demonstrate the potential for therapeutic interventions for SCI, and I am hopeful for what our future research will find.”

The researchers are now seeking funding for a Phase 2a trial studying the safety and tolerability of the drug in those with SCI.

Source: King’s College London

Categories : NeurologyTags :

Source of Hidden Consciousness in ‘Comatose’ Brain Injury Patients Found

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Researchers have identified brain injuries that may underlie hidden consciousness, a puzzling phenomenon in which brain-injured patients are unable to respond to simple commands, making them appear unconscious despite having some level of awareness.

“Our study suggests that patients with hidden consciousness can hear and comprehend verbal commands, but they cannot carry out those commands because of injuries in brain circuits that relay instructions from the brain to the muscles,” says study leader Jan Claassen, MD, associate professor of neurology at Columbia University.

The findings, published in the journal Brain, could help physicians more quickly identify brain-injured patients who might have hidden consciousness and better predict which patients are likely to recover with rehabilitation.

Brain circuits disrupted in patients with hidden consciousness

Hidden consciousness, also known as cognitive motor dissociation (CMD), occurs in 15–25% of patients with brain injuries stemming from head trauma, brain haemorrhage, or cardiac arrest.

In previous research, Claassen and colleagues found that subtle brainwaves detectable with EEG are the strongest predictor of hidden consciousness and eventual recovery for unresponsive brain-injured patients.

But the precise pathways in the brain that become disrupted in this condition were unknown.

In the new study, the researchers used EEG to examine 107 brain injury patients. The technique can determine when patients are trying, though unable, to respond to a command such as “keep opening and closing your right hand.”

The analysis detected CMD in 21 of the patients. The researchers then analysed structural MRI scans from all of the patients.

“Using a technique we developed called bi-clustering analysis, we were able to identify patterns of brain injury that are shared among patients with CMD and contrast to those without CMD,” says co-lead author Qi Shen, PhD, associate research scientist in the Claassen lab.

The researchers found that all of the CMD patients had intact brain structures related to arousal and command comprehension, supporting the notion that these patients were hearing and understanding the commands but were unable to carry them out.

“We saw that all of the CMD patients had deficits in brain regions responsible for integrating comprehended motor commands with motor output, preventing CMD patients from acting on verbal commands,” says Claassen.

The findings may allow researchers to better understand which brain injury patients have CMD, which will be useful for clinical trials that support recovery of consciousness.

More research is required before these approaches can be applied to clinical practice. “However, our study shows that it may be possible to screen for hidden consciousness using widely available structural brain imaging, moving the detection of CMD one step closer to general clinical use,” Claassen says.

“Not every critical care unit may have resources and staff that is trained in using EEG to detect hidden consciousness, so MRI may offer a simple way to identify patients who require further screening and diagnosis.”

Source: Columbia University Irving Medical Center

Categories : Implants and Prostheses NeurologyTags :

For Stroke Recovery, Deep Brain Stimulation may Aid Rehabilitation

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Deep brain stimulation illustration. Credit: NIH

A first-in-human trial of deep brain stimulation (DBS) for post-stroke rehabilitation patients has shown that using DBS to target the dentate nucleus – which regulates fine-control of voluntary movements, cognition, language, and sensory functions in the brain – is safe and feasible.

The EDEN trial (Electrical Stimulation of the Dentate Nucleus for Upper Extremity Hemiparesis Due to Ischemic Stroke) also shows that the majority of participants (9 of 12) demonstrated improvements in both motor impairment and function. Importantly, the study found that participants with at least minimal preservation of distal motor function at enrolment showed gains that almost tripled their initial scores.

Published in Nature Medicine, these findings build on more than a decade of preclinical work led by principal investigators Andre Machado, MD, PhD, and Kenneth Baker, PhD, at Cleveland Clinic.

“These are reassuring for patients as the participants in the study had been disabled for more than a year and, in some cases, three years after stroke. This gives us a potential opportunity for much needed improvements in rehabilitation in the chronic phases of stroke recovery,” said Dr Machado, patented the DBS method in stroke recovery. “The quality-of-life implications for study participants who responded to therapy have been significant.”

“We saw patients in the study regain levels of function and independence they did not have before enrolling in the research,” Dr Machado said. “This was a smaller study and we look forward to expanding as we have begun the next phase.”

The completed EDEN trial enrolled 12 individuals with chronic, moderate-to-severe hemiparesis of the upper extremity as a result of a unilateral middle cerebral artery stroke 12-to-36 months prior. There were no major complications throughout the study. Nine of the 12 participants improved to a degree that is considered meaningful in stroke rehabilitation.

Source: Cleveland Clinic

Categories : Cancer NeurologyTags :

In A First, Immunotherapy for Glioblastoma Successfully Tested in Mice

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Photo by Kanashi ZD on Unsplash

Immunotherapy has dramatically improved survival against many cancers but efforts to use it against glioblastomas have to date proven fruitless. Now, Salk scientists have found the immunotherapy treatment anti-CTLA-4 leads to considerably greater survival of mice with glioblastoma. Furthermore, they discovered that this therapy was dependent on immune cells called CD4+ T cells infiltrating the brain and triggering the tumour-destructive activities of other immune cells called microglia, which permanently reside in the brain.

The findings, published in the journal Immunity, show the benefit of harnessing the body’s own immune cells to fight brain cancer and could lead to more effective immunotherapies for treating brain cancer in humans.

Glioblastoma, the most common and deadly form of brain cancer, grows rapidly to invade and destroy healthy brain tissue. The tumour sends out cancerous tendrils into the brain that make surgical tumour removal extremely difficult or impossible.

“There are currently no effective treatments for glioblastoma – a diagnosis today is basically a death sentence,” says Professor Susan Kaech, senior author and director of the NOMIS Center for Immunobiology and Microbial Pathogenesis. “We’re extremely excited to find an immunotherapy regimen that uses the mouse’s own immune cells to fight the brain cancer and leads to considerable shrinkage, and in some cases elimination, of the tumour.”

For some tumours, immunotherapy can be used, in which the body’s own immune cells to seek and destroy cancer cells, leading to strong, lasting anti-cancer responses for many patients. Kaech sought new ways of harnessing the immune system to develop more safe and durable treatments for brain cancer.

Her team found three cancer-fighting tools that have been somewhat overlooked in brain cancer research that may cooperate and effectively attack glioblastoma: an immunotherapy drug called anti-CTLA-4 and specialized immune cells called CD4+ T cells and microglia.

Anti-CTLA-4 immunotherapy works by blocking cells from making the CTLA-4 protein, which, if not blocked, inhibits T cell activity. It was the first immunotherapy drug designed to stimulate our immune system to fight cancer, but it was quickly followed by another, anti-PD-1, that was less toxic and became more widely used. Whether anti-CTLA-4 is an effective treatment for glioblastoma remains unknown since anti-PD-1 took precedence in clinical trials. Unfortunately, anti-PD-1 was found to be ineffective in multiple clinical trials for glioblastoma – a failure that inspired Kaech to see whether anti-CTLA-4 would be any different.

As for the specialized immune cells, CD4+ T cells are often overlooked in cancer research in favour of a similar immune cell, the CD8+ T cell, because CD8+ T cells are known to directly kill cancer cells. Microglia live in the brain full time, where they patrol for invaders and respond to damage – whether they play any role in tumour death was not clear. When treated with anti-CLA-4, mice with glioblastoma had longer lifespans than those receiving anti-PD-1.

Upon investigation, they found that after anti-CTLA-4 treatment, CD4+ T cells secreted a protein called interferon gamma that caused the tumour to throw up “stress flags” while simultaneously alerting microglia to start eating up those stressed tumour cells. As they gobbled up the tumour cells, the microglia would present scraps of tumour on their surface to keep the CD4+ T cells attentive and producing more interferon gamma, creating a cycle that lasts until the tumour is destroyed.

“Our study demonstrates the promise of anti-CTLA-4 and outlines a novel process where CD4+ T cells and other brain-resident immune cells team up to kill cancerous cells,” says co-first author Dan Chen, a postdoctoral researcher in Kaech’s lab.

To understand the role of microglia in this cycle, the researchers collaborated with co-author and Salk Professor Greg Lemke. For decades, Lemke has investigated critical molecules, called TAM receptors, used by microglia to send and receive crucial messages. The researchers found that TAM receptors told microglia to gobble up cancer cells in this novel cycle.

“We were stunned by this novel codependency between microglia and CD4+ T cells,” says co-first author Siva Karthik Varanasi, a postdoctoral researcher in Kaech’s lab. “We are already excited about so many new biological questions and therapeutic solutions that could radically change treatment for deadly cancers like glioblastoma.”

Connecting the pieces of this cancer-killing puzzle brings researchers closer than ever to understanding and treating glioblastoma.

“We can now reimagine glioblastoma treatment by trying to turn the local microglia that surround brain tumours into tumour killers,” says Kaech. “Developing a partnership between CD4+ T cells and microglia is creating a new type of productive immune response that we have not previously known about.”

Next, the researchers will examine whether this cancer-killing cell cycle is present in human glioblastoma cases. Additionally, they aim to look at other animal models with differing glioblastoma subtypes, expanding their understanding of the disease and optimal treatments.

Source: Salk Institute

Categories : NeurologyTags :

Study Resolves Long-standing Question on Gating of Ion Channels

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Source: CC0

Ion channels play a crucial role in many cellular processes, including neuronal communication, muscle contraction or cell proliferation. Most multi subunit ion channels exist in two functional states, either closed or open. During gating, one should expect that all subunits undergo conformational changes – but there are no intermediate conduction levels. To find out why, researchers from the University of Vienna and the Washington University in St. Louis created a smart model system. The study is currently published in Nature Communications.

Ion channels are membrane proteins that regulate the electrical activity of cells. In this study the scientific team investigated the inwardly rectifying potassium channel Kir2. This channel is crucial for maintaining a negative membrane potential in many cells. These channels are promising drug targets for treatment of cardiovascular diseases. To foster drug development, a detailed understanding of the gating mechanism is important.

Intelligent model system & innovative methods

“We designed a model system that allowed us to visualise the gating of individual subunits and track conductance changes,” explains Grigory Maksaev from the Washington University in St. Louis. As a model system, the inwardly rectifying potassium channel Kir2 was used. This channel is crucial for maintaining a negative membrane potential in many cells. “We introduced an acidic residue near the channel gate. This led to novel states, so-called sub-conductance states” explains Eva Plessl from the Department of Pharmaceutical Sciences, University of Vienna. The life times of these sub-states were long enough to resolve them experimentally. Each of the observed sub-states represents a distinct subunit conformation. Interestingly, the sub-state occupancy is titratable by pH. “This suggests that protonation or deprotonation of individual acidic residues causes this phenomenon,” explains Sun-Joo Lee from the Washington University in St. Louis.

Sour is…less conductive

“Molecular dynamics simulations with different protonation states of the acidic residue support this finding,” explains Anna Weinzinger from the Department of Pharmaceutical Sciences, University of Vienna. The study reveals that each subunit gating transition leads to conductance level changes. This suggests that for a fully open channel, all subunits must move together. “By designing a smart model system, we have answered a long-standing question about ion channel gating,” explains Colin Nichols from the Washington University in St. Louis.

Source: University of Vienna

Categories : Gastrointestinal NeurologyTags :

Possible Dementia Risk from Long Term Proton Pump Inhibitor Use

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Source: Pixabay CC0

People who take proton pump inhibitors for acid reflux four-and-a-half years or more may have a higher risk of dementia compared to people who do not take these medications, according to new research published in Neurology.

Acid reflux is when stomach acid flows into the oesophagus, usually after a meal or when lying down, resulting in heartburn and ulcers. People with frequent acid reflux may develop gastroesophageal reflux disease, or GERD, which can lead to cancer of the oesophagus. Proton pump inhibitors reduce stomach acid by targeting the enzymes in the stomach lining that produce that acid.

“Proton pump inhibitors are a useful tool to help control acid reflux, however long-term use has been linked in previous studies to a higher risk of stroke, bone fractures and chronic kidney disease,” said study author Kamakshi Lakshminarayan, MBBS, PhD, of the University of Minnesota School of Public Health in Minneapolis, and a member of the American Academy of Neurology. “Still, some people take these drugs regularly, so we examined if they are linked to a higher risk of dementia. While we did not find a link with short-term use, we did find a higher risk of dementia associated with long-term use of these drugs.”

The study included 5712 people, aged 45 and up, without dementia at the start of the study. They had an average age of 75.

Researchers determined if participants took acid reflux drugs by reviewing their medications during study visits and during yearly phone calls. Of the participants, 1490 people, or 26%, had taken the drugs. Participants were then divided into four groups based on whether they had taken the drugs and for how long, as follows: people who did not take the drugs; those who took the drugs for up to 2.8 years; those who took them for 2.8 to 4.4 years; and people who took them for more than 4.4 years.

Participants were then followed for a median duration of 5.5 years. During this time, 585 people, or 10%, developed dementia.

Of the 4222 people who did not take the drugs, 415 people developed dementia, or 19 cases per 1000 person-years. Person-years represent both the number of people in the study and the amount of time each person spends in the study. Of the 497 people who took the drugs for more than 4.4 years, 58 people developed dementia, or 24 cases per 1000 person-years.

After adjusting for factors such as age, sex and race, as well as health-related factors such as high blood pressure and diabetes, researchers found people who had been taking acid reflux drugs for more than 4.4 years had a 33% higher risk of developing dementia than people who never took the drugs.

Researchers did not find a higher risk of dementia for people who took the drugs for fewer than 4.4 years.

“More research is needed to confirm our findings and explore reasons for the possible link between long-term proton pump inhibitor use and a higher risk of dementia,” said Lakshminarayan. “While there are various ways to treat acid reflux, such as taking antacids, maintaining a healthy weight, and avoiding late meals and certain foods, different approaches may not work for everyone. It is important that people taking these medications speak with their doctor before making any changes, to discuss the best treatment for them, and because stopping these drugs abruptly may result in worse symptoms.”

A limitation of the study was that participants were asked once a year about medication use, so researchers estimated use between annual check-ins. If participants stopped and restarted acid reflux drugs in between check-ins, estimation of their use may have been inaccurate. The authors were also unable to assess if participants took over the counter acid reflux drugs.

Source: American Academy of Neurology

Categories : Neurology PaediatricsTags :

Newly Identified Lipid in Breast Milk Might Reduce Cerebral Palsy in Infants

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Ten percent of babies born before 32 weeks will develop cerebral palsy resulting from infections that damage white matter, nerve fibres deep in the brain. While it’s known that the white matter loss will lead to neurological deficits, there is currently no treatment to avoid this.

Now, researchers at Duke Health have conducted experiments using neonatal mice and identified a fatty molecule in breast milk that triggers a process in which stem cells in the brain produce cells that create new white matter, reversing the injury.

The study appears in the journal Cell Stem Cell. Corresponding author Eric Benner, MD, PhD, said that further study in a clinical trial is needed, but the finding is promising.

“Developing therapies for children – especially such medically fragile children – is very difficult to do because there are justifiably strict safety concerns,” Benner said. “The fact that this molecule is already found in something that is safe for premature babies – breast milk – is extremely encouraging.

“It’s been known that fats in breast milk benefit a child’s brain development, but there are many types of fats in breast milk,” Benner said. “This work has identified a lipid molecule in breast milk that promotes white matter development. Now, we can begin to develop a therapy that isolates and delivers this lipid in a way that is safe for the unique challenges of these infants.”

Benner is a neonatologist at Duke University and one of the co-founders of Tellus Therapeutics, a Duke spinout company developed with the help of the Duke University Office for Translation & Commercialization to bring this therapy from the bench into the neonatal intensive care unit.

The fatty molecule identified in the study will be administered intravenously to patients in an upcoming clinical trial. This is significant because many of the infants who are part of this vulnerable population also have gastrointestinal issues and cannot safely be given milk or medication by mouth.

The lipid molecule enters the brain and binds with stem cells there, encouraging the stem cells to become or produce a type of cell called oligodendrocytes.

The oligodendrocytes are like a hub that allow for the production of white matter in the central nervous system. This newly produced white matter in pre-term infants prevents the neurological damage that would otherwise impact the child’s ability to move – the hallmarks of cerebral palsy.

“The timing of brain injury is extremely difficult to predict, thus a treatment that could be safely given to all preterm babies at risk would be revolutionary,” said Agnes Chao, MD, a former fellow in the Division of Neonatology and first author of the paper.

“As a neonatologist, I’m so excited that I may be able to offer a treatment to families with babies that are affected by preterm brain injury who would otherwise have no other options,” Chao said.

Source: Duke University Medical Center

Categories : NeurologyTags :

Night-time Fragrances Provide Cognitive Boost that Could Stave off Dementia

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When a fragrance wafted through the bedrooms of older adults for two hours every night for six months, memory recall skyrocketed. Participants in this study experienced a 226% increase in cognitive capacity compared to controls. The researchers say the finding transforms the long-known tie between smell and memory into an easy, non-invasive technique for strengthening memory and potentially deterring dementia. The findings, which appear to pass the ‘sniff test’, are published in the open-access journal Frontiers in Neuroscience.

The project was conducted University of California, Irvine neuroscientists, involving men and women aged 60 to 85 without memory impairment. All were given a diffuser and seven cartridges, each containing a single and different natural oil. People in the enriched group received full-strength cartridges. Control group participants were given the oils in tiny amounts. Participants put a different cartridge into their diffuser each evening prior to going to bed, and it activated for two hours as they slept.

People in the enriched group showed a 226% increase in cognitive performance compared to the control group, as measured by a word list test commonly used to evaluate memory. Imaging revealed better integrity in the brain pathway called the left uncinate fasciculus. This pathway, which connects the medial temporal lobe to the decision-making prefrontal cortex, becomes less robust with age. Participants also reported sleeping more soundly.

Scientists have long known that the loss of olfactory capacity, or ability to smell, can predict development of nearly 70 neurological and psychiatric diseases. These include Alzheimer’s and other dementias, Parkinson’s, schizophrenia and alcoholism. Evidence is emerging about a link between smell loss due to COVID and ensuing cognitive decrease. Researchers have previously found that exposing people with moderate dementia to up to 40 different odours twice a day over a period of time boosted their memories and language skills, eased depression and improved their olfactory capacities. The UCI team decided to try turning this knowledge into an easy and non-invasive dementia-fighting tool.

“The reality is that over the age of 60, the olfactory sense and cognition starts to fall off a cliff,” said Michael Leon, professor of neurobiology & behaviour and a CNLM fellow. “But it’s not realistic to think people with cognitive impairment could open, sniff and close 80 odorant bottles daily. This would be difficult even for those without dementia.”

The study’s first author, project scientist Cynthia Woo, said: “That’s why we reduced the number of scents to just seven, exposing participants to just one each time, rather than the multiple aromas used simultaneously in previous research projects. By making it possible for people to experience the odors while sleeping, we eliminated the need to set aside time for this during waking hours every day.”

The researchers say the results from their study bear out what scientists learned about the connection between smell and memory.

“The olfactory sense has the special privilege of being directly connected to the brain’s memory circuits,” said collaborating investigator Michael Yassa, professor and director of CNLM. “All the other senses are routed first through the thalamus. Everyone has experienced how powerful aromas are in evoking recollections, even from very long ago. However, unlike with vision changes that we treat with glasses and hearing aids for hearing impairment, there has been no intervention for the loss of smell.”

The team would next like to study the technique’s impact on people with diagnosed cognitive loss. The researchers also say they hope the finding will lead to more investigations into olfactory therapies for memory impairment. A product based on their study and designed for people to use at home is expected to come onto the market later this year.

Source: University of California – Irvine

Categories : NeurologyTags :

A Curious Mindset Helps Memory More than an Urgent One

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Photo by Mari Lezhava on Unsplash

New research from Duke University found that shifting to a curious mindset helps memory – such as video game players who imagined being a thief scouting a virtual art museum in preparation for a heist. This mindset resulted in better recalling the paintings there. Adopting a high-pressure mindset, such as players trying to execute the heist, resulted in fewer paintings being recalled.

These subtle differences in motivation – urgent, immediate goal-seeking versus curious exploration for a future goal – have big potential for framing real-world challenges such encouraging vaccination. The findings appeared in PNAS.

Alyssa Sinclair, PhD ’23, a postdoctoral researcher working in the lab of Duke Institute for Brain Sciences director Alison Adcock, PhD, MD, recruited 420 adults to pretend to be art thieves for a day. The participants were then randomly assigned to one of two groups and received different backstories.

“For the urgent group, we told them, ‘You’re a master thief, you’re doing the heist right now. Steal as much as you can!’,” Sinclair said. “Whereas for the curious group, we told them they were a thief who’s scouting the museum to plan a future heist.”

After getting these different backstories, however, participants in the two groups played the exact same computer game, scored the exact same way. They explored an art museum with four coloured doors, representing different rooms, and clicked on a door to reveal a painting from the room and its value. Some rooms held more valuable collections of art. No matter which scenario they were pretending to be in, everyone earned real bonus money by finding more valuable paintings.

The impact of this difference in mindset was most apparent the following day. When participants logged back in, they were met with a pop quiz about whether they could recognise 175 different paintings (100 from the day before, and 75 new ones). If participants flagged a painting as familiar, they also had to recall how much it was worth.

Sinclair and her co-author, fellow Duke psychology & neuroscience graduate student Candice Yuxi Wang, were gratified after they graded the tests to see their predictions had played out.

“The curious group participants who imagined planning a heist had better memory the next day,” Sinclair said. “They correctly recognized more paintings. They remembered how much each painting was worth. And reward boosted memory, so valuable paintings were more likely to be remembered. But we didn’t see that in the urgent group participants who imagined executing the heist.”

Urgent group participants, however, had a different advantage. They were better at figuring out which doors hid more expensive pieces, and as a result snagged more high value paintings. Their stash was appraised at about $230 more than the curious participants’ collection.

The difference in strategies (curious versus urgent) and their outcomes (better memory versus higher-valued paintings) doesn’t mean one is better than the other, though.

“It’s valuable to learn which mode is adaptive in a given moment and use it strategically,” Dr Adcock said.

For example, being in an urgent, high-pressure mode might be the best option for a short-term problem.

“If you’re on a hike and there’s a bear, you don’t want to be thinking about long-term planning,” Sinclair said. “You need to focus on getting out of there right now.”

Opting for an urgent mindset might also be useful in less grisly scenarios that require short-term focus, Sinclair explained, like prompting people to get a COVID vaccine.

For encouraging long-term memory or action, stressing people out is less effective.

“Sometimes you want to motivate people to seek information and remember it in the future, which might have longer term consequences for lifestyle changes,” Sinclair said. “Maybe for that, you need to put them in a curious mode so that they can actually retain that information.”

Sinclair and Wang are now following up on these findings to see how urgency and curiosity activate different parts of the brain. Early evidence suggests that, by engaging the amygdala, an almond-shaped brain region best known for its role in fear memory, “urgent mode” helps form focused, efficient memories. Curious exploration, however, seems to shuttle the learning-enhancing neurochemical dopamine to the hippocampus, a brain region crucial for forming detailed long-term memories.

With these brain results in mind, Dr Adcock is exploring how her lab’s research might also benefit the patients she sees as a psychiatrist.

“Most of adult psychotherapy is about how we encourage flexibility, like with curious mode” Dr Adcock said. “But it’s much harder for people to do since we spend a lot of our adult lives in an urgency mode.”

These thought exercises may give people the ability to manipulate their own neurochemical spigots and develop “psychological manoeuvres,” or cues that act similar to pharmaceuticals, Dr Adcock explained.

“For me, the ultimate goal would be to teach people to do this for themselves,” Dr Adcock said. “That’s empowering.”

Source: Duke University

Categories : Immune System NeurologyTags :

Study Reveals How The Brain Detects and Regulates Inflammation

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Source: CC0

A study published in the journal Neuron has revealed the existence of a circuit in the brain that senses and regulates the anti-inflammatory response, including the triggering of behaviours associated with sickness and releasing cortisone, a potent negative regulator of immune responses. This circuit embodies a two-way connection between the brain and immune system.

Whenever infections or injuries occur, the immune system is triggered to control the infection and repair damaged tissue. This process involves the release of pro-inflammatory mediators that inform the brain of the body’s immune status and coordinate the immune response. In response to this signal, the brain sets off a complex reaction known as ‘sickness behaviour’ whose purpose is to reassign energy to the body’s different systems. This state is associated with behavioural changes including social avoidance and lethargy, metabolic adjustments such as fever and loss of appetite, and the release of hormones such as cortisone, to increase resistance to infection while also regulating immune responses.

In this study, a multidisciplinary group consisting of neurobiologists and immunologists from the Institut Pasteur, Inserm and the CNRS discovered a novel circuit used by the brain to measure inflammation levels in the blood and, in response to this, regulate inflammation. A region of the brainstem known as the vagal complex directly detects levels and types of inflammatory hormones in the bloodstream. This information is then relayed to neurons in another region of the brainstem called the parabrachial nucleus, which also receives information related to pain and certain aversive or traumatic memories. In turn, these neurons activate neurons in the hypothalamus leading to a rapid increase in cortisone in the blood.

The scientists used state-of-the-art neuroscience approaches to identify this circuit, which enabled them to individually observe the neurons involved during inflammation. The experts observed how the activity of specific neurons in the parabrachial nucleus could regulate the production of white blood cells involved in the immune response. “This research demonstrates that neural activity in the brain alone can have a powerful effect on the development of immune responses during infection or injury. It therefore provides a clear example of the powerful two-way connection between the body and brain. It also fuels our ambition to discover the impact of our brain on the way we interact with microbes, fight off pathogens and heal wounds,” explains Gérard Eberl, Head of the Institut Pasteur’s Microenvironment and Immunity Unit.

The discovery of this circuit opens up new opportunities for research that will jointly contribute to the fields of neurobiology and immunology: “This study gives us additional tools to better understand the impact of systemic inflammation on our brain, mood and on certain neurodegenerative processes,” adds Gabriel Lepousez, a neurobiologist in the Perception and Memory Unit (Institut Pasteur/CNRS).

Given the established role of the parabrachial nucleus in aversive memory processes, potential infectious threats could be averted if this circuit is reactivated by the memory of past inflammatory or aversive experiences. Drawing on this neuro-immune communication, the immune system could therefore benefit from the brain’s ability to predict and anticipate threats in our environment.

Source: Institut Pasteur