Category: Neurology

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Brains do Not Actually ‘Rewire’ Themselves, Scientists Argue

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Ischaemic and haemorrhagic stroke. Credit: Scientific Animations CC4.0

Contrary to the commonly-held view, the brain does not have the ability to rewire itself to compensate for conditions such as stroke, loss of sight or an amputation, say scientists in the journal eLife.

Professors Tamar Makin of Cambridge University and John Krakauer of Johns Hopkins University argue that the notion that the brain, in response to injury or deficit, can reorganise itself and repurpose particular regions for new functions, is fundamentally flawed – despite being commonly cited in scientific textbooks. Instead, they argue that what is occurring is merely the brain being trained to utilise already existing, but latent, abilities.

One of the most common examples given is where a person loses their sight – or is born blind – and the visual cortex, previously specialised in processing vision, is rewired to process sounds, allowing the individual to use a form of ‘echolocation’ to navigate a cluttered room. Another common example is of people who have had a stroke and are initially unable to move their limbs repurposing other areas of the brain to allow them to regain control.

Krakauer, Director of the Center for the Study of Motor Learning and Brain Repair at Johns Hopkins University, said: “The idea that our brain has an amazing ability to rewire and reorganise itself is an appealing one. It gives us hope and fascination, especially when we hear extraordinary stories of blind individuals developing almost superhuman echolocation abilities, for example, or stroke survivors miraculously regaining motor abilities they thought they’d lost.

“This idea goes beyond simple adaptation, or plasticity – it implies a wholesale repurposing of brain regions. But while these stories may well be true, the explanation of what is happening is, in fact, wrong.”

In their article, Makin and Krakauer look at a ten seminal studies that purport to show the brain’s ability to reorganise. They argue, however, that while the studies do indeed show the brain’s ability to adapt to change, it is not creating new functions in previously unrelated areas – instead it’s utilising latent capacities that have been present since birth.

For example, a 1980s study by Professor Michael Merzenich at University of California, San Francisco looked at what happens when a hand loses a finger. The hand has a particular representation in the brain, with each finger appearing to map onto a specific brain region. Remove the forefinger, and the area of the brain previously allocated to this finger is reallocated to processing signals from neighbouring fingers, argued Merzenich – in other words, the brain has rewired itself in response to changes in sensory input.

Not so, says Makin, whose own research provides an alternative explanation.

In a study published in 2022, Makin used a nerve blocker to temporarily mimic the effect of amputation of the forefinger in her subjects. She showed that even before amputation, signals from neighbouring fingers mapped onto the brain region ‘responsible’ for the forefinger — in other words, while this brain region may have been primarily responsible for process signals from the forefinger, it was not exclusively so. All that happens following amputation is that existing signals from the other fingers are ‘dialled up’ in this brain region.

Makin, from the Medical Research Council (MRC) Cognition and Brain Sciences Unit at the University of Cambridge, said: “The brain’s ability to adapt to injury isn’t about commandeering new brain regions for entirely different purposes. These regions don’t start processing entirely new types of information. Information about the other fingers was available in the examined brain area even before the amputation, it’s just that in the original studies, the researchers didn’t pay much notice to it because it was weaker than for the finger about to be amputated.”

Another compelling counterexample to the reorganisation argument is seen in a study of congenitally deaf cats, whose auditory cortex appears to be repurposed to process vision. But when they are fitted with a cochlear implant, this brain region immediately begins processing sound once again, suggesting that the brain had not, in fact, rewired.

Examining other studies, Makin and Krakauer found no compelling evidence that the visual cortex of individuals that were born blind or the uninjured cortex of stroke survivors ever developed a novel functional ability that did not otherwise exist.

Makin and Krakauer do not dismiss stories such as blind people navigating using hearing, or individuals who have experienced a stroke regain their motor functions. They argue instead that rather than completely repurposing regions for new tasks, the brain is enhancing or modifying its pre-existing architecture — and it is doing this through repetition and learning.

Understanding the true nature and limits of brain plasticity is crucial, both for setting realistic expectations for patients and for guiding clinical practitioners in their rehabilitative approaches, they argue.

Makin added: “This learning process is a testament to the brain’s remarkable – but constrained – capacity for plasticity. There are no shortcuts or fast tracks in this journey. The idea of quickly unlocking hidden brain potentials or tapping into vast unused reserves is more wishful thinking than reality. It’s a slow, incremental journey, demanding persistent effort and practice. Recognising this helps us appreciate the hard work behind every story of recovery and adapt our strategies accordingly.

“So many times, the brain’s ability to rewire has been described as ‘miraculous’ – but we’re scientists, we don’t believe in magic. These amazing behaviours that we see are rooted in hard work, repetition and training, not the magical reassignment of the brain’s resources.”

The original text of this story is licensed under a Creative Commons Licence.

Source: University of Cambridge

Categories : NeurologyTags :

Why do Some People get a ‘Red Wine’ Headache?

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For some people, drinking red wine even in small amounts causes a headache, which typically occurs within 30 minutes to three hours after drinking as little as a small glass of wine. Researchers have examined why this happens – even to people who don’t get headaches when drinking small amounts of other alcoholic beverages. In their work, published in the journal Scientific Reports, the researchers posit that a flavanol found naturally in red wines can interfere with the proper metabolism of alcohol and can lead to a headache.

The headache culprit: Quercetin, a flavanol

This flavanol is called quercetin and it is naturally present in all kinds of fruits and vegetables, including grapes. It’s considered a healthy antioxidant and is even available in supplement form. But when metabolized with alcohol, it can be problematic.

“When it gets in your bloodstream, your body converts it to a different form called quercetin glucuronide,” said wine chemist and corresponding author Andrew Waterhouse, professor emeritus with the UC Davis Department of Viticulture and Enology. “In that form, it blocks the metabolism of alcohol.”

Acetaldehyde toxin buildup leads to flushing, headache, nausea

As a result, people can end up accumulating the toxin acetaldehyde, explains lead author Apramita Devi, postdoctoral researcher with the UC Davis Department of Viticulture and Enology.

“Acetaldehyde is a well-known toxin, irritant and inflammatory substance,” said Devi. “Researchers know that high levels of acetaldehyde can cause facial flushing, headache and nausea.”

The medication disulfiram prescribed to alcoholics to prevent them from drinking causes these same symptoms. Waterhouse said that’s because the drug also causes the toxin to build up in the body when normally an enzyme in the body would break it down. About 40% of the East Asian population also has an enzyme that doesn’t work very well, allowing acetaldehyde to build up in their system.

“We postulate that when susceptible people consume wine with even modest amounts of quercetin, they develop headaches, particularly if they have a preexisting migraine or another primary headache condition,” said co-author Morris Levin, professor of neurology and director of the Headache Center at the University of California, San Francisco. “We think we are finally on the right track toward explaining this millennia-old mystery. The next step is to test it scientifically on people who develop these headaches, so stay tuned.”

Sunlight increases headache-causing flavanol in grapes

Waterhouse said levels of this flavanol can vary dramatically in red wine.

“Quercetin is produced by the grapes in response to sunlight,” Waterhouse said. “If you grow grapes with the clusters exposed, such as they do in the Napa Valley for their cabernets, you get much higher levels of quercetin. In some cases, it can be four to five times higher.”

Levels of quercetin can also differ depending on how the wine is made, including skin contact during fermentation, fining processes and aging.

Clinical trial on wine headaches

Scientists will next compare red wines that contain a lot of quercetin with those that have very little to test their theory about red wine headaches on people. This small human clinical trial, funded by the Wine Spectator Scholarship Foundation, will be led by UCSF.

Researchers said there are still many unknowns about the causes of red wine headaches. It’s unclear why some people seem more susceptible to them than others. Researchers don’t know if the enzymes of people who suffer from red wine headaches are more easily inhibited by quercetin or if this population is just more easily affected by the buildup of the toxin acetaldehyde.

“If our hypothesis pans out, then we will have the tools to start addressing these important questions,” Waterhouse said.

Source: University of California – Davis

Categories : Cancer NeurologyTags :

Lung Cancer Metastases in the Brain Trick Astrocytes for Protection

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Small cell lung cancer cells (green and blue) that metastasised to the brain in a laboratory mouse recruit brain cells called astrocytes (red) for their protection. Credit: Fangfei Qu

Lung cancer cells that metastasise to the brain survive by convincing brain cells called astrocytes that they are baby neurons in need of protection, according to a study by researchers at Stanford Medicine published in Nature Cell Biology.

The cancer cells carry out their subterfuge by secreting a chemical signal prevalent in the developing human brain, the researchers found. This signal draws astrocytes to the tumour, encouraging them to secrete other factors that promote the cancer cells’ survival. Blocking that signal may be one way to slow or stop the growth of brain metastases of small cell lung cancer, which account for about 10% to 15% of all lung cancers, the researchers believe.

In the adult brain, astrocytes play a critical role in maintaining nerve function and connectivity. They are also important during brain development, when they facilitate connections between developing neurons.

The researchers studied laboratory mice, human tissue samples and human mini-brains, or organoids, grown in a lab dish to dissect the unique relationship between the cancer cells and their ‘big sister’ astrocytes, which hover nearby and shower them with protective factors.

“Small cell lung cancers are known for their ability to metastasise to the brain and thrive in an environment that is not normally conducive to tumour growth,” said professor of paediatrics and of genetics Julien Sage, PhD. “Our study suggests that these cancer cells reprogram the brain microenvironment by recruiting astrocytes for their protection.”

Professor Sage is the senior author of the study, while postdoctoral scholar Fangfei Qu, PhD, is the lead author.

Invasion of the brain

Small cell lung cancer excels at metastasising to the brain – about 15% to 20% of people already have clusters of cancer cells in their brains when their lung tumours are first diagnosed. As the cancer progresses, about 40% to 50% of patients will develop brain metastases. The problem is so prevalent, and the clinical outcome so dire, that clinicians recommend cranial radiation even before brain metastases have been found.

How and why small cell lung cancer has such an affinity for the brain has been something of a mystery. Brain metastases are rarely biopsied or removed because doing so has not been shown to affect a patient’s survival, and brain surgery is so invasive. Using laboratory mice is also of little help since small cell lung cancers in those animals rarely develop metastases in the brain, perhaps due to subtle biological differences between species.

Small cell lung cancers have another distinguishing feature – they are neuroendocrine cancers, meaning they arise from cells with similarities to both neurons and hormone-producing cells. Neuroendocrine cells link the nervous system with the endocrine system throughout the body, including in the lung.

Sage and his colleagues wondered whether neuronal-associated proteins on the surface of small cell lung cancer cells give them a leg up when the cells first begin to infiltrate the brain.

“We know the brain is full of neurons,” Sage said. “Maybe that’s why these cancer cells with some neuronal traits are happy in the brain and are accepted into that environment.”

Qu and Sage developed a way to inject mouse small cell lung cancer cells grown in the laboratory into the brains of mice to spark the development of brain tumours. They saw that astrocytes, a subtype of glial cell, flocked to the infant tumours and began to churn out proteins critical during brain development, including factors that stimulate nerve growth.

A plethora of astrocytes

A similar call happens in human brains, they noted: Brain tissue samples from people who had died of metastatic small cell lung cancer, shared by professor of pathology and paper co-author Christina Kong, MD, had many more protective astrocytes in the interior of the tumours than did metastases of melanoma, breast cancer and another type of lung cancer called adenocarcinoma.

Qu worked with assistant professor of paediatrics and co-author Anca Pasca, MD, to fuse aggregates of small cell lung cancer, lung adenocarcinoma or breast cancer cells with what are called cortical organoids – in vitro-grown clumps of brain cells including neurons and astrocytes that begin to mimic the organisation and connectivity of a human cortex. Within 10 days, many more protective astrocytes had infiltrated the small cell lung cancer pseudo-tumours than the adenocarcinoma or breast cancer.

“This showed us that the astrocytes actively move toward the small cell lung cancer cells, rather than simply being engulfed by the growing tumour,” Sage said. “What’s more exciting, though, is that these organoids, or mini-brains, realistically model the developing human brain. So, we’re no longer relying on a mouse model. It’s a perfect system to study brain metastases.”

Further research showed that the small cell lung cancer cells summon protective astrocytes by secreting a protein called Reelin that mediates the migration of neuronal and glial cells during brain development. Triggering Reelin expression in mouse breast cancer cells injected into the brain significantly increased the number of astrocytes in the resulting tumours in the mice, and the tumours were larger than in control animals injected with cells with low Reelin expression.

The apparent reliance of the cancer cells on chemical signals and responses specific to the developing brain may give clues for the development of future therapies, Sage believes.

“Some of these signals may not be as relevant or as highly expressed in the adult brain,” Sage said. “As a result, perhaps they could still be targeted to slow or prevent brain metastases without harming a normal brain. This might be an important window of opportunity for therapy.”

Source: Stanford Medicine

Categories : Cancer NeurologyTags :

A Living Biobank of Brain Metastasis Samples will Unlock New Research

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Photo by National Cancer Institute on Unsplash

At 18 Spanish hospitals, when a patient with brain metastasis undergoes surgery, they can donate a tiny part of their brain to the first repository of brain metastasis living samples in the world, based at the Spanish National Cancer Research Centre (CNIO). A world-first collection, it was created to accelerate the search for therapies against brain metastasis, a disease that affects up to 30% of patients with systemic cancer.

The creators of this repository, called RENACER (Spanish acronym for the National Brain Metastasis Network), are two CNIO researchers, Manuel Valiente, head of the Brain Metastasis Group, and Eva Ortega-Paíno, director of the Biobank. They explained the advantages of the collection in the journal Trends in Cancer. In just three years RENACER has compiled samples from more than 150 patients.

The truly unique feature of RENACER, which makes it a valuable tool for the international scientific community, is that it contains living samples, conserved in cultures that enable the cells to continue behaving in a similar way as they were in the body.

A living biobank that enables organotypic cultures

“We have built a ‘living’ biobank” write Valiente and Ortega-Paíno. And this characteristic can be “transformative, not only for research but also for clinical trial design, especially when focused on unmet clinical needs, such as brain metastasis”.

The fact that the cells are living allows them, for example, to study their response to specific drugs. RENACER paves the way to create avatars for each patient in order to identify the best therapeutic options in an individualised way.

“Research contracts have been already signed to exploit patient-derived organotypic cultures (PDOCs) as avatars, thus providing the possibility to generate biomarkers of sensitivity or resistance to specific drugs” the authors explain.

The hospitals involved with RENACER work as a network to pass on research findings to patients as quickly as possible. In fact, thanks to this network, there are already two clinical trials underway, which will determine the capacity of two biomarkers to discriminate cases in which radiotherapy – a technique with side effects – will be effective.

From the operating theatre to the biobank in hours

The requirement for cells to be “alive” is not easy to achieve, since it involves a sophisticated logistics chain. The samples are taken from the operating theatre in a special container, in their culture medium, at a temperature of between 4 and 8 degrees centigrade.

They must reach the CNIO Biobank, in Madrid, in less than 24 hours. There, they are processed, organotypic cultures are created, and they are divided into proportional parts that are stored as samples for future investigations. They are also analysed using various techniques and sequenced, to extract as much information as possible from them. All the data are put into a database that is open to the international scientific community.

“It is pivotal to empower patients”

“This is happening just a few years after the project was launched,” said Valiente. “It’s a strategy that helps to improve knowledge as well as diagnosis and treatment options, but also brings all the people involved closer together: patients, core researchers, chemical re searchers, healthcare professionals, and the biobank.”

Patients, “[because they act] as donors during a difficult brain metastasis neurosurgery, play a crucial role and we strongly believe that it is pivotal to empower them,” the researchers explain. GEPAC (Spanish Group of Patients with Cancer) is also involved with RENACER.

Source: Spanish National Cancer Research Centre (CNIO)

Categories : Mental Health NeurologyTags :

Fear is in the Eye of the Beholder, Researchers Find

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Looking away from something frightening may be due to a specific cluster of neurons in a visual region of the brain, according to new research at the University of Tokyo. Researchers found that, in fruit fly brains, these neurons release a chemical called tachykinin which appears to control the fly’s movement to avoid facing a potential threat. Fruit fly brains can offer a useful analogy for larger mammals, so this study, published in Nature Communications, may help studies of human reactions to fearful situations and phobias.

“We discovered a neuronal mechanism by which fear regulates visual aversion in the brains of Drosophila (fruit flies). It appears that a single cluster of 20-30 neurons regulates vision when in a state of fear. Since fear affects vision across animal species, including humans, the mechanism we found may be active in humans as well,” explained Assistant Professor Masato Tsuji from the Department of Biological Sciences at the University of Tokyo.

The team used puffs of air to simulate a physical threat and found that the flies’ walking speed increased after being puffed at. The flies also would choose a puff-free route if offered, showing that they perceived the puffs as a threat (or at least preferred to avoid them). Next the researchers placed a small black object, roughly the size of a spider, 60 degrees to the right or left of the fly. On its own the object didn’t cause a change in behavior, but when placed following puffs of air, the flies avoided looking at the object and moved so that it was positioned behind them.

To understand the molecular mechanism underlying this aversion behavior, the team then used mutated flies in which they altered the activity of certain neurons. While the mutated flies kept their visual and motor functions, and would still avoid the air puffs, they did not respond in the same fearful manner to visually avoid the object.

“This suggested that the cluster of neurons which releases the chemical tachykinin was necessary for activating visual aversion,” said Tsuji. “When monitoring the flies’ neuronal activity, we were surprised to find that it occurred through an oscillatory pattern, ie, the activity went up and down similar to a wave. Neurons typically function by just increasing their activity levels, and reports of oscillating activity are particularly rare in fruit flies because up until recently the technology to detect this at such a small and fast scale didn’t exist.”

By giving the flies genetically encoded calcium indicators, the researchers could make the flies’ neurons shine brightly when activated. Thanks to the latest imaging techniques, they then saw the changing, wavelike pattern of light being emitted, which was previously averaged out and missed.

Next, the team wants to figure out how these neurons fit into the broader circuitry of the brain. Although the neurons exist in a known visual region of the brain, the researchers do not yet know from where the neurons are receiving inputs and to where they are transmitting them, to regulate visual escape from objects perceived as dangerous.

“Our next goal is to uncover how visual information is transmitted within the brain, so that we can ultimately draw a complete circuit diagram of how fear regulates vision,” said Tsuji. “One day, our discovery might perhaps provide a clue to help with the treatment of psychiatric disorders stemming from exaggerated fear, such as anxiety disorders and phobias.”

Source: University of Tokyo

Categories : Neurology Pain ManagementTags :

How Sleep Disruption Can Make Pain Feel Worse

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People often experience headaches and body pain after a lack of sleep, but the mechanisms behind this phenomenon are unclear. A new study published in Nature Communications reveals that a certain endocannabinoid neurotransmitter plays a major role.

The animal-based study, led by investigators at Massachusetts General Hospital (MGH), a founding member of Mass General Brigham (MGB), found that the heightened pain sensitivity than can result from chronic sleep disruption (CSD) – or CSD-induced hyperalgaesia – involved signalling from a part of a brain known as the thalamic reticular nucleus (TRN).

Analyses of metabolites showed that the level of N-arachidonoyl dopamine (NADA), a type of neurotransmitter called an endocannabinoid, decreased in the TRN as a result of sleep deprivation.

Activity of the cannabinoid receptor 1, which is involved in controlling pain perception, also decreased in the thalamic reticular nucleus after CSD.

Administering NADA to the TRN reduced CSD-induced hyperalgaesia in mice.

This beneficial effect of administered NADA could be countered by blocking the cannabinoid receptor 1, suggesting that both the receptor and NADA play a role in pain sensitivity due to sleep deprivation.

“We provide a mechanism as to how sleep disruption leads to exaggerated pain, suggesting that harnessing the endocannabinoid system might break the vicious cycle between pain and sleep loss,” says co-senior author Shiqian Shen, MD, the clinical director of MGH’s Tele Pain Program.

Source: Massachusetts General Hospital

Categories : NeurologyTags :

Scientists Record Powerful Signals in the Brain’s White Matter

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Scientists have concentrated on the grey matter of the cortex, composed of nerve cell bodies , while ignoring white matter, composed of axons, even though it makes up half the brain. Now, in the Proceedings of the National Academy of Sciences, Vanderbilt University researchers report strong signs of brain activity when performing certain tasks.

For several years, John Gore, PhD, director of the Vanderbilt University Institute of Imaging Science, and his colleagues have used functional magnetic resonance imaging (fMRI) to detect blood oxygenation-level dependent (BOLD) signals, a key marker of brain activity, in white matter.

In this latest paper, the researchers report that when people who are having their brains scanned by fMRI perform a task, like wiggling their fingers, BOLD signals increase in white matter throughout the brain.

“We don’t know what this means,” said the paper’s first author, Kurt Schilling, PhD, research assistant professor of Radiology and Radiological Sciences at VUMC. “We just know that something is happening. There truly is a powerful signal in the white matter.”

It is important to pursue this because disorders as diverse as epilepsy and multiple sclerosis disrupt the “connectivity” of the brain, Schilling said. This suggests that something is going on in white matter.

To find out, the researchers will continue to study changes in white matter signals they’ve previously detected in schizophrenia, Alzheimer’s disease and other brain disorders. Through animal studies and tissue analysis, they also hope to determine the biological basis for these changes.

In grey matter, BOLD signals reflect a rise in blood flow (and oxygen) in response to increased nerve cell activity.

Perhaps the axons, or the glial cells that maintain the protective myelin sheath around them, also use more oxygen when the brain is ‘working’. Or perhaps these signals are somehow related to what’s going on in the grey matter.

But even if nothing biological is going on in white matter, “there’s still something happening here,” Schilling said. “The signal is changing. It’s changing differently in different white matter pathways and it’s in all white matter pathways, which is a unique finding.”

One reason that white matter signals have been understudied is that they have lower energy than grey matter signals, and thus are more difficult to distinguish from the brain’s background “noise.”

The VUMC researchers boosted the signal-to-noise ratio by having the person whose brain was being scanned repeat a visual, verbal or motor task many times to establish a trend and by averaging the signal over many different white matter fibre pathways.

“For 25 or 30 years, we’ve neglected the other half of the brain,” Schilling said. Some researchers not only have ignored white matter signals but have removed them from their reports of brain function.

The Vanderbilt findings suggest that many fMRI studies thus “may not only underestimate the true extent of brain activation, but also … may miss crucial information from the MRI signal,” the researchers concluded.

Source: Vanderbilt University

Categories : Mental Health NeurologyTags :

The Eyes may Hold the Secret to the Greatest Benefits from TMS Therapy

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A pair of recently published studies from researchers at UCLA Health suggest that measuring changes in how pupils react to light could help predict recovery from depression and personalise transcranial magnetic stimulation (TMS) treatment of major depressive disorder.

TMS is a safe, non-invasive therapy that uses magnetic fields to stimulate parts of the brain involved in mood regulation. While TMS is proven effective, not all patients respond equally well to the therapy. The ability to predict who will benefit most could allow doctors to better customise and target treatments.

In two recent studies, UCLA scientists found that the pupil’s response to light before treatment correlated with improvements in depression symptoms over the course of therapy. Pupil size reflects activation of the autonomic nervous system, which controls involuntary functions and is negatively impacted in people with depression.

The first study, appearing in the Journal of Affective Disorders, reports on outcomes for 51 patients who underwent daily TMS sessions. Before receiving treatment, researchers measured the patients’ baseline pupillary constriction amplitude, or CA: how much the pupil shrinks when exposed to light. The pupil’s constriction is an indicator of parasympathetic nervous system function. The researchers found a significant association between baseline pupil constriction amplitude and symptom improvement, indicating that a greater constriction amplitude at baseline was associated with a better outcome. In other words, those with larger pupil constriction in response to light at baseline showed greater symptom improvement over their full treatment.

The second study, published in Brain Stimulation, went further and compared patients who were treated for depression with one of two common TMS protocols: 10Hz stimulation and intermittent theta burst stimulation (iTBS). In 10Hz stimulation, magnetic pulses are delivered in a continuous and relatively high-frequency stimulation. iTBS is a faster form of stimulation with bursts of three pulses at 50Hz, repeated with short breaks between bursts. This pattern is thought to mimic the natural rhythm of certain brain activities.

The researchers found that people with slower pupillary constriction had significantly greater improvement in depression after 10 sessions if they received iTBS rather than 10Hz treatment.

“These results suggest we may be able to use a simple test of the pupil to identify who is most likely to respond to electromagnetic stimulation of the brain to treat their depression,” said researcher Cole Citrenbaum, lead author of both studies.

Tailored TMS treatments

The researchers propose that measuring pupillary reactivity before starting TMS could guide treatment selection. “Additionally, we may be able to tailor the frequency of stimulation to the individual patient to maximise their benefit from treatment,” Citrenbaum said.

“At the present time, about 65% of patients treated with TMS have a substantial improvement in their depression,” said Dr Andrew F. Leuchter, senior author of both studies. “Our goal is to have more than 85% of patients fully recover from depression. As we better understand the complex brain activity underlying depression, we move closer to matching patients with the treatments that ensure their full recovery. Pupil testing may be one useful tool in reaching this goal.”

The studies add to growing evidence on the benefits of biologically-based personalization in treating major depression. UCLA researchers plan further trials to confirm the value of pupillometry in optimizing transcranial magnetic stimulation.

Source: University of California – Los Angeles Health Sciences

Categories : NeurologyTags :

Converting Brain Immune Cells into Neurons Boosts Stroke Recovery in Mice

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Source: CC0

Japanese researchers have turned microglia (brain immune cells) into neurons, successfully restoring brain function after stroke-like injury in mice. These findings, published in PNAS, suggest that replenishing neurons from immune cells could be a promising avenue for treating stroke in humans.

Recovery from stroke, where blood supply to neurons is disrupted by blockage or bleeding, is often poor, with patients suffering from severe physical disabilities and cognitive problems.

“When we get a cut or break a bone, our skin and bone cells can replicate to heal our body. But the neurons in our brain cannot easily regenerate, so the damage is often permanent,” says Professor Kinichi Nakashima, from Kyushu University’s Graduate School of Medical Sciences. “We therefore need to find new ways to replace lost neurons.”

One possible strategy is to convert other cells in the brain into neurons. Here, the researchers focused on microglia, the main immune cells in the central nervous system. Microglia are tasked with removing damaged or dead cells in the brain, so after a stroke, they move towards the site of injury and replicate quickly.

“Microglia are abundant and exactly in the place we need them, so they are an ideal target for conversion,” says first author Dr Takashi Irie, from Kyushu University Hospital.

In prior research, the team demonstrated that they could coax microglia to develop into neurons in the brains of healthy mice. Dr Irie and Professor Nakashima and colleagues, now showed that this strategy of replacing neurons also works in injured brains and contributes to brain recovery.

To conduct the study, the researchers caused a stroke-like injury in mice by temporarily blocking the right middle cerebral artery — a major blood vessel in the brain that is commonly associated with stroke in humans. A week later, the researchers examined the mice and found that they had difficulties in motor function and had a marked loss of neurons in a brain region known as the striatum. This part of the brain is involved in decision making, action planning and motor coordination.

The researchers then used a lentivirus to insert DNA into microglial cells at the site of the injury. The DNA held instructions for producing NeuroD1, a protein that induces neuronal conversion. Over the subsequent weeks, the infected cells began developing into neurons and the areas of the brain with neuron loss decreased. By eight weeks, the new induced neurons had successfully integrated into the brain’s circuits.

At only three weeks post-infection, the mice showed improved motor function in behavioural tests. These improvements were lost when the researchers removed the new induced neurons, providing strong evidence that the newly converted neurons directly contributed to recovery.

“These results are very promising. The next step is to test whether NeuroD1 is also effective at converting human microglia into neurons and confirm that our method of inserting genes into the microglial cells is safe,” says Professor Nakashima.

Furthermore, the treatment was conducted in mice in the acute phase after stroke, when microglia were migrating to and replicating at the site of injury. Therefore, the researchers also plan to see if recovery is also possible in mice at a later, chronic phase.

Source: Kyushu University

Categories : Lab Tests and Imaging NeurologyTags :

AI-based CT Scans of the Brain can Nearly Match MRI

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A new artificial intelligence (AI)-based method can provide as much information on subtle neurodegenerative changes in the brain captured by computed tomography (CT) as compared to magnetic resonance imaging (MRI). The method, reported in the journal Alzheimer’s & Dementia, could enhance diagnostic support, particularly in primary care, for conditions such as dementia and other brain disorders.

Compared to MRI, which requires powerful superconducting magnetics and their associated cryogenic cooling, computed tomography (CT) is a relatively inexpensive and widely available imaging technology. CT is considered inferior to MRI when it comes to reproducing subtle structural changes in the brain or flow changes in the ventricular system. Certain imaging must therefore currently be carried out by specialist departments at larger hospitals equipped with MRI.

AI trained on MRI images

Created with deep learning, a form of AI, the software has been trained to transfer interpretations from MRI images to CT images of the same brains. The new software can provide diagnostic support for radiologists and other professionals who interpret CT images.

“Our method generates diagnostically useful data from routine CT scans that, in some cases, is as good as an MRI scan performed in specialist healthcare,” says Michael Schöll, a professor at Sahlgrenska Academy who led the work involved in the study, carried out in collaboration with researchers at Karolinska Institutet, the National University of Singapore, and Lund University

“The point is that this simple, quick method can provide much more information from examinations that are already carried out on a routine basis within primary care, but also in certain specialist healthcare investigations. In its initial stage, the method can support dementia diagnosis, however, it is also likely to have other applications within neuroradiology.”

Reliable decision-making support

This is a well-validated clinical application of AI-based algorithms, and has the potential to become a fast and reliable form of decision-making support that effectively reduces the number of false negatives. The researchers believe that this solution can improve diagnostics in primary care, optimising patient flow to specialist care.

“This is a major step forward for imaging diagnosis,” says Meera Srikrishna, a postdoctor at the University of Gothenburg and lead author of the study.

“It is now possible to measure the size of different structures or regions of the brain in a similar way to advanced analysis of MRI images. The software makes it possible to segment the brain’s constituent parts in the image and to measure its volume, even though the image quality is not as high with CT.”

Applications for other brain diseases

The software was trained on images of 1117 people, all of whom underwent both CT and MRI imaging. The current study mainly involved healthy older individuals and patients with various forms of dementia. Another application that the team is now investigating is for normal pressure hydrocephalus (NPH).

With NPH, the team has obtained new results indicating that the method can be used both during diagnosis and to monitor the effects of treatment. NPH is a condition that occurs particularly in older people, whereby fluid builds up in the cerebral ventricular system and results in neurological symptoms. About two percent of all people over the age of 65 are affected. Because diagnosis can be complicated and the condition risks being confused with other diseases, many cases are likely to be missed.

“NPH is difficult to diagnose, and it can also be hard to safely evaluate the effect of shunt surgery to drain the fluid in the brain,” continues Michael. “We therefore believe that our method can make a big difference when caring for these patients.”

The software has been developed over the course of several years, and development is now continuing in cooperation with clinics in Sweden, the UK, and the US together with a company, which is a requirement for the innovation to be approved and transferred to healthcare.

Source: University of Gothenburg