Category: Neurology

Progress and Challenges in the Development of Brain Implants

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In a paper recently published in The Lancet Digital Health, a scientific team led by Stanisa Raspopovic from MedUni Vienna looks at the progress and challenges in the research and development of brain implants. New achievements in the field of this technology are seen as a source of hope for many patients with neurological disorders and have been making headlines recently. As neural implants have an effect not only on a physical but also on a psychological level, researchers are calling for particular ethical and scientific care when conducting clinical trials.

The research and development of neuroprostheses has entered a phase in which experiments on animal models are being followed by tests on humans. Only recently, reports of a paraplegic patient in the USA who was implanted with a brain chip as part of a clinical trial caused a stir. With the help of the implant, the man can control his wheelchair, operate the keyboard on his computer and use the cursor in such a way that he can even play chess. About a month after the implantation, however, the patient realised that the precision of the cursor control was decreasing and the time between his thoughts and the computer actions was delayed.

“The problem could be partially, but not completely, resolved – and illustrates just one of the potential challenges for research into this technology,” explains study author Stanisa Raspopovic from MedUni Vienna’s Center for Medical Physics and Biomedical Engineering, who published the paper together with Marcello Ienca (Technical University of Munich) and Giacomo Valle (ETH Zurich). “The questions of who will take care of the technical maintenance after the end of the study and whether the device will still be available to the patient at all after the study has been cancelled or completed are among the many aspects that need to be clarified in advance in neuroprosthesis research and development, which is predominantly industry-led.”

Protection of highly sensitive data

Neuroprostheses establish a direct connection between the nervous system and external devices and are considered a promising approach in the treatment of neurological impairments such as paraplegia, chronic pain, Parkinson’s disease and epilepsy. The implants can restore mobility, alleviate pain or improve sensory functions. However, as they form an interface to the human nervous system, they also have an effect on a psychological level: “They can influence consciousness, cognition and affective states and even free will. This means that conventional approaches to safety and efficacy assessment, such as those used in clinical drug trials, are not suitable for researching these complex systems. New models are needed to comprehensively evaluate the subjective patient experience and protect the psychological privacy of the test subjects,” Raspopovic points out.

The special technological features of neuroimplants, in particular the ability to collect and process neuronal data, pose further challenges for clinical validation and ethical oversight. Neural data is considered particularly sensitive and requires an even higher level of protection than other health information. Unsecured data transmission, inadequate data protection guidelines and the risk of hacker attacks are just some of the potential vulnerabilities that require special precautions in this context. “The use of neural implants cannot be reduced to medical risks,” summarises Stanisa Raspopovic. “We are only in the initial phase of clinical studies on these technological innovations. But questions of ethical and scientific diligence in dealing with this highly sensitive topic should be clarified now and not only after problems have arisen in test subjects or patients.”

Source: Medical University of Vienna

Could the Key to IBS Treatment Lie in the Brain?

Irritable bowel syndrome. Credit: Scientific Animations CC4.0

Although irritable bowel syndrome (IBS) affects about a tenth of the global population, the underlying causes and mechanisms of IBS remain unclear and thus treatments focus on symptom management. At Tokyo University of Science (TUS), Japan, Professor Akiyoshi Saitoh and his research group have spent the past decade exploring this topic. This study, published in the British Journal of Pharmacology, discovered that a class of drugs called opioid delta-receptor (DOP) agonists may help alleviate IBS symptoms by targeting the central nervous system rather than acting directly on the intestine.

One of the main motivations for this study was the growing evidence linking IBS closely to psychological stress. Saitoh’s group aimed to address this potential root cause by focusing on finding a novel animal model for this condition. In a 2022 study, they developed a mice model repeatedly exposed to psychological stress – using a method called chronic vicarious social defeat stress (cVSDS) – which developed symptoms similar to a type of IBS called IBS-D. These symptoms included overly active intestines and heightened sensitivity to abdominal pain, even though their organs showed no physical damage. The cVSDS animal model involved having the subject mouse repeatedly witness a territorial, aggressive mouse defeating a cage mate, inducing indirect chronic stress.

Using the cVSDS model, the researchers sought to determine whether DOP in the brain, which is closely linked to pain and mood regulation, could serve as promising drug targets for treating stress-induced IBS. To achieve this, they performed a series of detailed experiments to observe the effects of DOP agonists on IBS symptoms and chemical signaling in the brain. Some experiments involved measuring the speed of a charcoal meal through the intestine to assess gastrointestinal motility and evaluate the impact of stress or treatments on bowel movement speed, along with directly measuring neurotransmitter concentrations using in vivo brain microdialysis. This revealed that re-exposure to VSDS increased glutamate levels in the insular cortex, but these elevated levels were normalised with DOP agonists.

According to the results, the administration of DOP agonists helped relieve abdominal pain and regulated bowel movements in cVSDS mice. Interestingly, applying the DOP agonists directly to a specific brain region called the insular cortex had similar effects on IBS symptoms as systemic treatment. “Our findings demonstrated that DOP agonists acted directly on the central nervous system to improve diarrhoea-predominant IBS symptoms in mice, and suggest that the mechanism of action involves the regulation of glutamate neurotransmission in the insular cortex,” highlights Saitoh.

Taken together, the continued research by Saitoh’s group on this topic could pave the way for effective treatments for IBS. “DOP agonists could represent a groundbreaking new IBS treatment that not only improves IBS-like symptoms but also provides anti-stress and emotional regulation effects. In the future, we would like to conduct clinical developments with the goal of expanding the indication of DOP agonists for IBS, in addition to depression,” remarks Saitoh.

Compared to currently available IBS treatments, such as laxatives, antidiarrhoeals, analgesics, and antispasmodics, targeting the underlying stress with DOP agonists may offer a more definitive solution with minimal adverse effects. Further clarification of the roles of stress and brain chemistry in the development of IBS will be essential in achieving this much-needed medical breakthrough. With promising prospects, future studies will translate Saitoh’s group’s findings to humans, bringing great relief to those affected by IBS.

Source: Tokyo University of Science

New Tech could Cut Epilepsy Misdiagnoses by up to 70% Using Routine EEGs

Source: Pixabay

Doctors could soon reduce epilepsy misdiagnoses by up to 70% using a new tool that turns routine electroencephalogram, or EEG, tests that appear normal into highly accurate epilepsy predictors, a Johns Hopkins University study has found.

By uncovering hidden epilepsy signatures in seemingly normal EEGs, the tool could significantly reduce false positives, seen in around 30% of cases globally, and spare patients from medication side effects, driving restrictions, and other quality-of-life challenges linked to misdiagnoses.

“Even when EEGs appear completely normal, our tool provides insights that make them actionable,” said Sridevi V. Sarma, a Johns Hopkins biomedical engineering professor who led the work. “We can get to the right diagnosis three times faster because patients often need multiple EEGs before abnormalities are detected, even if they have epilepsy. Accurate early diagnosis means a quicker path to effective treatment.”

A report of the study is newly published in Annals of Neurology.

Epilepsy causes recurrent, unprovoked seizures triggered by bursts of abnormal electrical activity in the brain. Standard care involves scalp EEG recordings during initial evaluations. These tests track brainwave patterns using small electrodes placed on the scalp.

Clinicians partly rely on EEGs to diagnose epilepsy and decide whether patients need anti-seizure medications. However, EEGs can be challenging to interpret because they capture noisy signals and because seizures rarely occur during the typical 20 to 40 minutes of an EEG recording. These characteristics makes diagnosing epilepsy subjective and prone to error, even for specialists, Sarma explained.

To improve reliability, Sarma’s team studied what happens in the brains of patients when they are not experiencing seizures. Their tool, called EpiScalp, uses algorithms trained on dynamic network models to map brainwave patterns and identify hidden signs of epilepsy from a single routine EEG.

“If you have epilepsy, why don’t you have seizures all the time? We hypothesized that some brain regions act as natural inhibitors, suppressing seizures. It’s like the brain’s immune response to the disease,” Sarma said.

The new study analyzed 198 epilepsy patients from five major medical centers: Johns Hopkins Hospital, Johns Hopkins Bayview Medical Center, University of Pittsburgh Medical Center, University of Maryland Medical Center, and Thomas Jefferson University Hospital. Out of these 198 patients in the study, 91 patients had epilepsy while the rest had non-epileptic conditions mimicking epilepsy.

When Sarma’s team reanalysed the initial EEGs using EpiScalp, the tool ruled out 96% of those false positives, cutting potential misdiagnoses among these cases from 54% to 17%.

“This is where our tool makes a difference because it can help us uncover markers of epilepsy in EEGs that appear uninformative, reducing the risk of patients being misdiagnosed and treated for a condition they don’t have,” said Khalil Husari, co-senior author and assistant professor of neurology at Johns Hopkins. “These patients experienced side effects of the anti-seizure medication without any benefit because they didn’t have epilepsy. Without the correct diagnosis, we can’t find out what’s actually causing their symptoms.”

In certain cases, misdiagnosis happens due to misinterpretation of EEGs, Husari explained, as doctors may overdiagnose epilepsy to prevent the dangers of a second seizure. But in some cases, patients experience nonepileptic seizures, which mimic epilepsy. These conditions can often be treated with therapies that do not involve epilepsy medication.

In earlier work, the team studied epileptic brain networks using intracranial EEGs to demonstrate that the seizure onset zone is being inhibited by neighboring regions in the brain when patients are not seizing. EpiScalp builds on this research, identifying these patterns from routine scalp EEGs.

Traditional approaches to improve EEG interpretation often focus on individual signals or electrodes. Instead, EpiScalp analyses how different regions of the brain interact and influence one another through a complex network of neural pathways, said Patrick Myers, first author and doctoral student in biomedical engineering at Johns Hopkins.

“If you just look at how nodes are interacting with each other within the brain network, you can find this pattern of independent nodes trying to cause a lot of activity and the suppression from nodes in a second region, and they’re not interacting with the rest of the brain,” Myers said. “We check whether we can see this pattern anywhere. Do we see a region in your EEG that has been decoupled from the rest of the brain’s network? A healthy person shouldn’t have that.”

Source: Johns Hopkins University

Elevated Opioid Neurotransmitter Activity Seen in Patients with Anorexia

Photo from Freepik.

A study conducted at Turku PET Centre in Finland and published in showed that changes in the functioning of opioid neurotransmitters in the brain may underlie anorexia.

Anorexia nervosa is a serious psychiatric disorder characterised by restricted eating, fear of gaining weight, and body image disturbances, which may lead to severe malnutrition, depression and anxiety. This new study from Turku PET Centre, published in Molecular Psychiatry, shows how changes in neurotransmitter function in the brain may underlie anorexia.

“Opioid neurotransmission regulates appetite and pleasure in the brain. In patients with anorexia nervosa, the brain’s opioidergic tone was elevated in comparison with healthy control subjects. Previously we have shown that in obese patients the activity of the tone of this system is lowered. It is likely that the actions of these molecules regulate both the loss and increase in appetite,” says Professor Pirjo Nuutila from the University of Turku.

Number of opioid receptors in the brain (top row) and sugar intake (bottom row) in patients with anorexia nervosa. Credit: University of Turku

In addition, the researchers measured the brain’s glucose uptake. The brain accounts for about 20% of the body’s total energy consumption, so the researchers were interested in how a reduction in the energy intake affects the brain’s energy balance in anorexia.

“The brains of patients with anorexia nervosa used a similar amount of glucose as the brains of the healthy control subjects. Although being underweight burdens physiology in many ways, the brain tries to protect itself and maintain its ability to function for as long as possible,” says Professor Lauri Nummenmaa from Turku PET Centre and continues:

“The brain regulates appetite and feeding, and changes in brain function are associated with both obesity and low body weight. Since changes in opioid activity in the brain are also connected to anxiety and depression, our findings may explain the emotional symptoms and mood changes associated with anorexia nervosa.”

Source: University of Turku

Nerve Stimulation Fails When the Brain is not ‘Listening’

A small device worn on the body can stimulate the nervous system via electrodes on the ear. Credit: Vienna University of Technology.

Various diseases can be treated by stimulating the vagus nerve in the ear with electrical signals, but the results can be ‘hit or miss’. A study recently published in Frontiers in Physiology has now shown that the electrical signals must be synchronised with the body’s natural rhythms – heartbeat and breathing.

Some health problems, from chronic pain and inflammation to neurological diseases, can also be treated by nerve stimulation, for example with the help of electrodes that are attached to the ear and activate the vagus nerve. This method is sometimes referred to as an ‘electric pill’.

However, vagus nerve stimulation does not always work the way it is supposed to. A study conducted by TU Wien (Vienna) in cooperation with the Vienna Private Clinic now shows how this can be improved: Experiments demonstrate that the effect is very good when the electrical stimulation is synchronised with the body’s natural rhythms – the actual heartbeat and breathing.

The ‘electric pill’ for the parasympathetic nervous system

The vagus nerve plays an important role in our body: it is the longest nerve of the parasympathetic nervous system, the part of the nervous system that is significantly involved in the precise control of the internal organs and blood circulation, and is responsible for recovery and building up the body’s own reserves. A branch of the vagus nerve also leads from the brain directly into the ear, which is why small electrodes in the ear can be used to activate the vagus nerve, stimulate the brain and thus influence various functions of the body.

“However, it turns out that this stimulation does not always produce the expected results,” says Prof Eugenijus Kaniusas from the Institute of Biomedical Electronics at TU Wien. “The electrical stimulation does not have an effect on the nervous system at all times. You could say that the brain is just not always listening. It’s as if there is a gate to the control centre of the nervous system that is sometimes open and then closed again, and this can change in less than a second.”

Five people have now been examined in a pilot study. Their vagus nerve was electrically activated to lower their heart rate. It is already known from previous studies that heart rate is a potential indicator of whether stimulation therapy is beneficial or not.

It was shown that the temporal connection between the stimulation and the heartbeat plays a decisive role. If the vagus nerve is stimulated at a rhythm that is not synchronised with the heartbeat, hardly any effect can be observed. However, if the stimulation signals are always applied when the heart is contracting (during systole), a strong effect can be observed – much stronger than if stimulation is applied during the relaxation phase of the heart, diastole.

Breathing is also important in this context: the stimulation was significantly more effective during the inhalation phase than during the exhalation phase.

“Our results show that synchronising vagus nerve stimulation with the heartbeat and breathing rhythm significantly increases effectiveness. This could help to improve the success of treatment for chronic illnesses, especially for those who have not previously responded to this therapy for reasons that are as yet unexplained,” says Eugenijus Kaniusas.

Larger clinical studies to follow

If nerve stimulation can be customised electronically so that it is tailored to the body’s own individual rhythms at any given time, it should be possible to achieve significantly greater successes than has been possible to date. Future studies should examine larger and clinically relevant patient groups and develop even more precise algorithms in order to be able to tailor the stimulation even more precisely to individual needs.

“This technology could be an effective and non-invasive way of modulating the autonomic nervous system in a targeted and gentle manner – a potential milestone in the neuromodulatory treatment of various chronic diseases,” believes Dr Joszef Constantin Szeles from the Vienna Private Clinic.

Source: Vienna University of Technology

Researchers Map the Brain’s Self-healing Abilities after Stroke

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

A new study by researchers at the Department of Molecular Medicine at SDU sheds light on one of the most severe consequences of stroke: damage to nerve fibres – the brain’s “cables” – which leads to permanent impairments. The study, which is published in the Journal of Pathology, used unique tissue samples from Denmark’s Brain Bank located at SDU, may pave the way for new treatments that help the brain repair itself.

The brain tries to repair damage

Following an injury, the brain tries to repair the damaged nerve fibres by re-establishing their insulating myelin sheaths. Unfortunately, the repair process often succeeds only partially, meaning many patients experience lasting damage to their physical and mental functions. According to Professor Kate Lykke Lambertsen, one of the study’s lead authors, the brain has the resources to repair itself. “We need to find ways to help the cells complete their work, even under difficult conditions,” Prof Lykke said.

The researchers have thus focused on how inflammatory conditions hinder the rebuilding. The study has identified a particular type of cell in the brain that plays a key role in this process. These cells work to rebuild myelin, but inflammatory conditions often block their efforts.

How researchers used the brain collection

-Using the brain collection, we can precisely map which areas of the brain are most active in the repair process, explains Professor Kate Lykke Lambertsen.

This mapping has enabled researchers to analyse tissue samples from Denmark’s Brain Bank and gain a deeper understanding of the mechanisms that control the brain’s ability to heal itself.

Through advanced staining techniques, known as immunohistochemistry, the researchers have been able to detect specific cells that play a central role in the reconstruction of myelin in the damaged areas of the brain.

The samples were analysed to distinguish between different areas of the brain, including the infarct core (the most damaged area), the peri-infarct area (surrounding tissue where rebuilding is active), and tissue that appears unaffected.

The analysis provided insight into where repair cells accumulate and how their activity varies depending on gender and time since the stroke.

Women and men react differently

An interesting discovery in the study is that women’s and men’s brains react differently to injuries.

-The differences underscore the importance of future treatments being more targeted and taking into account the patient’s gender and individual needs, says Kate Lykke Lambertsen.

In women, it seems that inflammatory conditions can prevent cells from repairing damage, while men have a slightly better ability to initiate the repair process. This difference may explain why women often experience greater difficulties after a stroke.

The brain collection at SDU is key to progress

The researchers behind the study emphasise that the discoveries could not have been made without the Danish Brain Bank at SDU. The collection consists of tissue samples from humans, used to understand brain diseases at a detailed level.

With access to this resource, researchers can investigate the mechanisms behind diseases like stroke and develop new treatment strategies.

Source: University of Southern Denmark Faculty of Health Sciences

Person with Tetraplegia Pilots Drone with Brain-computer Interface

Photo by Thomas Bjornstad on Unsplash

A brain-computer interface, surgically placed in a research participant with tetraplegia, paralysis in all four limbs, provided an unprecedented level of control over a virtual quadcopter – just by thinking about moving his unresponsive fingers.

The technology divides the hand into three parts: the thumb and two pairs of fingers (index and middle, ring and small). Each part can move both vertically and horizontally. As the participant thinks about moving the three groups, at times simultaneously, the virtual quadcopter responds, manoeuvring through a virtual obstacle course.

It’s an exciting next step in providing those with paralysis the chance to enjoy games with friends while also demonstrating the potential for performing remote work.

“This is a greater degree of functionality than anything previously based on finger movements,” said Matthew Willsey, U-M assistant professor of neurosurgery and biomedical engineering, and first author of a new research paper in Nature Medicine. The testing that produced the paper was conducted while Willsey was a researcher at Stanford University, where most of his collaborators are located.

While there are noninvasive approaches to allow enhanced video gaming such as using electroencephalography to take signals from the surface of the user’s head, EEG signals combine contributions from large regions of the brain. The authors believe that to restore highly functional fine motor control, electrodes need to be placed closer to the neurons. The study notes a sixfold improvement in the user’s quadcopter flight performance by reading signals directly from motor neurons vs. EEG.

To prepare the interface, patients undergo a surgical procedure in which electrodes are placed in the brain’s motor cortex. The electrodes are wired to a pedestal that is anchored to the skull and exits the skin, which allows a connection to a computer.

“It takes the signals created in the motor cortex that occur simply when the participant tries to move their fingers and uses an artificial neural network to interpret what the intentions are to control virtual fingers in the simulation,” Willsey said. “Then we send a signal to control a virtual quadcopter.”

The quadcopter is on a serpentine path around rings that hang in midair over a virtual basketball court. The fingers of the hand are curled in with a line indicating a neutral point for the fingers. Four vectors point away from the thumb: up, down, right and left.
A screenshot of the game display shows the quadcopter following a green path around the rings. The inset shows a hand avatar. The neural implant records from nearby neurons and algorithms determine the intended movements for the hand avatar. The finger positions are then used to control the virtual quadcopter. Image credit: Nature Medicine

The research, conducted as part of the BrainGate2 clinical trials, focused on how these neural signals could be coupled with machine learning to provide new options for external device control for people with neurological injuries or disease. The participant first began working with the research team at Stanford in 2016, several years after a spinal cord injury left him unable to use his arms or legs. He was interested in contributing to the work and had a particular interest in flying.

“The quadcopter simulation was not an arbitrary choice, the research participant had a passion for flying,” said Donald Avansino, co-author and computer scientist at Stanford University. “While also fulfilling the participant’s desire for flight, the platform also showcased the control of multiple fingers.”

Co-author Nishal Shah, incoming professor of electrical and computer engineering at Rice University, explained, “controlling fingers is a stepping stone; the ultimate goal is whole body movement restoration.”

Jaimie Henderson, a Stanford professor of neurosurgery and co-author of the study, said the work’s importance goes beyond games. It allows for human connection.

“People tend to focus on restoration of the sorts of functions that are basic necessities – eating, dressing, mobility – and those are all important,” he said. “But oftentimes, other equally important aspects of life get short shrift, like recreation or connection with peers. People want to play games and interact with their friends.”

A person who can connect with a computer and manipulate a virtual vehicle simply by thinking, he says, could eventually be capable of much more.

“Being able to move multiple virtual fingers with brain control, you can have multifactor control schemes for all kinds of things,” Henderson said. “That could mean anything, from operating CAD software to composing music.”

Source: University of Michigan

Sex Differences are Also Seen in Brain Immune Cells

Image of an astrocyte, a subtype of glial cells. Glial cells are the most common cell in the brain. Credit: Pasca Lab, Stanford University
NIH support from: NINDS, NIMH, NIGMS, NCATS

New research from the University of Rochester finds that microglia function may not be as similar across sex as once thought. This discovery could have broad implications for how diseases like Alzheimer’s and Parkinson’s are approached and studied, and points to the necessity of having gender-specific research. It is already known that more women are diagnosed with Alzheimer’s and more men are diagnosed with Parkinson’s, but it’s unclear why.

Microglia are the immune cells of the central nervous system, clearing toxins in the brain. But if they are overactive, they can damage neurons instead and, in some cases, have been found to promote the progression of neurodegenerative diseases like Alzheimer’s and Parkinson’s. Although there are known sex-related differences in how microglia function, it was thought to be less variation in how they behave in adulthood. The new study showied how microglia respond differently in adult male versus female mice when given an enzyme inhibitor to block its microglia survival receptor.

“It is a fortuitous finding that has repercussions for what people are doing in the field, but also helps us understand microglia biology in a way that people may not have been expecting,” said Ania Majewska, PhD, professor of Neuroscience and senior author of the study in Cell Reports. “This research has a lot of ramifications for microglia biology and as a result all these diseases where microglia are important in a sex-specific manner.”

Pexidartinib or PLX3397 is an enzyme inhibitor commonly used to remove microglia in the lab setting to help researchers better understand the role of these cells in brain health, function, and disease. PLX3397 is also used to treat the rare disease tenosynovial giant cells tumours (TGCT), a condition that causes benign tumours to grow rapidly in the joints.

Researchers in the Majewska Lab were using PLX3397 in male versus female experiments but continued to run into difficulties, so they decided to take a different approach with the inhibitor. Instead of using it to ask other questions, they decided to better understand how microglia were responding to the drug in males versus females.

First author Linh Le, PhD (‘24), currently a Research Scientist, SetPoint Medical Corp, was a graduate student in the Majewska Lab when she found the expected response from microglia to PLX3397 in male mice: it blocked the receptor that signals microglial survival and depleted the microglia. However, Le, et al, were surprised to find that female microglia responded with a different signalling strategy that resulted in increased microglial survival and less depletion.

“These findings are crucial in the rapidly emerging field of developing disease-modifying therapies that target microglia,” said Majewska. “We do not yet know why the microglia are acting differently in the two sexes. I think we’d like to understand how the signaling through this receptor is regulated in different conditions, such as hormonal changes, basal state, inflammatory, or an anti-inflammatory state.”

Source: University of Rochester Medical Center

Brains of People with Sickle Cell Disease Appear Older

Sickle cell disease. Credit: National Institutes of Health

Individuals with sickle cell disease are at a higher risk for stroke and resulting cognitive disability. But even in the absence of stroke, many such patients struggle with remembering, focusing, learning and problem solving, among other cognitive problems, with many facing challenges in school and in the workplace.

Now a multidisciplinary team of researchers and physicians at Washington University School of Medicine in St. Louis has published a study that helps explain how the illness might affect cognitive performance in sickle cell patients without a history of stroke. The study, appearing in JAMA Network Open, found such participants had brains that appeared older than expected for their age. Individuals experiencing economic deprivation, who struggle to meet basic needs, even in the absence of sickle cell disease, had more-aged appearing brains, the team also found.

“Our study explains how a chronic illness and low socioeconomic status can cause cognitive problems,” said Andria Ford, MD, a professor of neurology and chief of the section of stroke and cerebrovascular diseases at WashU Medicine and corresponding author on the study. “We found that such factors could impact brain development and/or aging, which ultimately affects the mental processes involved in thinking, remembering and problem solving, among others. Understanding the influence that sickle cell disease and economic deprivation have on brain structure may lead to treatments and preventive measures that potentially could preserve cognitive function.”

More than 200 young, Black adults with and without sickle cell disease, living in St. Louis and the surrounding region in eastern Missouri and southwestern Illinois, participated in brain MRI scans and cognitive tests. The researchers – including Yasheng Chen, DSc, an associate professor of neurology at WashU Medicine and senior author on the study – calculated each person’s brain age using a brain-age prediction tool that was developed using MRI brain scans from a diverse group of more than 14 000 healthy people of known ages. The estimated brain age was compared with the individual’s actual age.

The researchers found that participants with sickle cell disease had brains that appeared an average of 14 years older than their actual age. Sickle cell participants with older-looking brains also scored lower on cognitive tests.

The study also found that socioeconomic status correlates with brain age. On average, a seven-year gap was found between the brain age and the participants’ actual age in healthy individuals experiencing poverty. The more severe the economic deprivation, the older the brains of such study subjects appeared.

Healthy brains shrink as people age, while premature shrinking is characteristic of neurological illnesses such as Alzheimer’s disease. But a smaller brain that appears older can also result from stunted growth early in life. Sickle cell disease is congenital, chronically depriving the developing brain of oxygen and possibly affecting its growth from birth. Also, children exposed to long-term economic deprivation and poverty experience cognitive challenges that affect their academic performance, Ford explained.

As a part of the same study, the researchers are again performing cognitive tests and scanning the brains of the same healthy and sickle cell participants three years after their first scan to investigate if the older-looking brains aged prematurely, or if their development was stunted.

“A single brain scan helps measure the participants’ brain age only in that moment,” said Ford, who treats patients at Barnes-Jewish Hospital. “But multiple time points can help us understand if the brain is stable, initially capturing differences that were present since childhood, or prematurely aging and able to predict the trajectory of someone’s cognitive decline. Identifying who is at greatest risk for future cognitive disability with a single MRI scan can be a powerful tool for helping patients with neurological conditions.”

Source: WashU Medicine

New Flexible ‘Tentacle’ Electrodes can Precisely Record Brain Activity

A bundle of extremely fine electrode fibres in the brain (microscope image). (Image: Yasar TB et al. Nature Communications 2024, modified)

Researchers at ETH Zurich have developed ultra-flexible brain probes that accurately record brain activity without causing tissue damage. This technology, described in Nature Communications, opens up new avenues for the treatment of a range of neurological and neuropsychiatric disorders. 

Neurostimulators, also known as brain pacemakers, send electrical impulses to specific areas of the brain via special electrodes. It is estimated that some 200 000 people worldwide are now benefiting from this technology, including those who suffer from Parkinson’s disease or from pathological muscle spasms. According to Mehmet Fatih Yanik, Professor of Neurotechnology at ETH Zurich, further research will greatly expand the potential applications: instead of using them exclusively to stimulate the brain, the electrodes can also be used to precisely record brain activity and analyse it for anomalies associated with neurological or psychiatric disorders. In a second step, it would be conceivable in future to treat these anomalies and disorders using electrical impulses.

To this end, Yanik and his team have now developed a new type of electrode that enables more detailed and more precise recordings of brain activity over an extended period of time. These electrodes are made of bundles of extremely fine and flexible fibres of electrically conductive gold encapsulated in a polymer. Thanks to a process developed by the ETH Zurich researchers, these bundles can be inserted into the brain very slowly, which is why they do not cause any detectable damage to brain tissue.

This sets the new electrodes apart from rival technologies. Of these, perhaps the best known in the public sphere is the one from Neuralink, an Elon Musk company. In all such systems, including Neuralink’s, the electrodes are considerably wider. “The wider the probe, even if it is flexible, the greater the risk of damage to brain tissue,” Yanik explains. “Our electrodes are so fine that they can be threaded past the long processes that extend from the nerve cells in the brain. They are only around as thick as the nerve-cell processes themselves.”

The tentacle electrodes (right) shown alongside three current technologies using thicker electrodes or an electrode mesh. (Yasar TB et al. Nature Communications 2024, modified)

The research team tested the new electrodes on the brains of rats using four bundles, each made up of 64 fibres. In principle, as Yanik explains, up to several hundred electrode fibres could be used to investigate the activity of an even greater number of brain cells. In the study, the electrodes were connected to a small recording device attached to the head of each rat, thereby enabling them to move freely.

No influence on brain activity

In the experiments, the research team was able to confirm that the probes are biocompatible and that they do not influence brain function. Because the electrodes are very close to the nerve cells, the signal quality is very good compared to other methods.

At the same time, the probes are suitable for long-term monitoring activities, with researchers recording signals from the same cells in the brains of animals for the entire duration of a ten-month experiment. Examinations showed that no brain-tissue damage occurred during this time. A further advantage is that the bundles can branch out in different directions, meaning that they can reach multiple brain areas.

Human testing to begin soon

In the study, the researcher used the new electrodes to track and analyse nerve-cell activity in various areas of the brains of rats over a period of several months. They were able to determine that nerve cells in different regions were “co-activated”. Scientists believe that this large-scale, synchronous interaction of brain cells plays a key role in the processing of complex information and memory formation. “The technology is of high interest for basic research that investigates these functions and their impairments in neurological and psychiatric disorders,” Yanik explains.

The group has teamed up with fellow researchers at the University College London in order to test diagnostic use of the new electrodes in the human brain. Specifically, the project involves epilepsy sufferers who do not respond to drug therapy. In such cases, neurosurgeons may remove a small part of the brain where the seizures originate. The idea is to use the group’s method to precisely localise the affected area of the brain prior to tissue removal.

Brain-machine interfaces

There are also plans to use the new electrodes to stimulate brain cells in humans. “This could aid the development of more effective therapies for people with neurological and psychiatric disorders”, says Yanik. In disorders such as depression, schizophrenia or OCD, there is often impairments in specific regions of the brain, which leads to problems in evaluation of information and decision making. Using the new electrodes, it might be possible to detect the pathological signals generated by the neural networks in the brain in advance, and then stimulate the brain in a way that would alleviate such disorders. Yanik also thinks that this technology may give rise to brain-machine interfaces for people with brain injuries. In such cases, the electrodes might be used to read their intentions and thereby, for example, to control prosthetics or a voice-output system.

Source: ETH Zurich