Category: Neurology

Brain Transmission Speeds Increase Until Middle Age

Source: CC0

It has been believed speed of information transmitted among regions of the brain stabilised during early adolescence. A study in Nature Neuroscience has instead found that transmission speeds continue to increase into early adulthood, which may explain the emergence of mental health problems over this period. In fact, transmission speeds increase until around age 40, reaching a speed twice that of a 4-year old child.

As mental health problems such as anxiety, depression and bipolar disorders can emerge in late adolescence and early adulthood, a better understanding of brain development may lead to new treatments.

“A fundamental understanding of the developmental trajectory of brain circuitry may help identify sensitive periods of development when doctors could offer therapies to their patients,” says senior author Dora Hermes, PhD, a biomedical engineer at Mayo Clinic.

Called the human connectome, the structural system of neural pathways in the brain or nervous system develops as people age. But how structural changes affect the speed of neuronal signalling has not been well described.

“Just as transit time for a truck would depend on the structure of the road, so does the transmission speed of signals among brain areas depend on the structure of neural pathways,” Dr Hermes explains. “The human connectome matures during development and aging, and can be affected by disease. All these processes may affect the speed of information flow in the brain.” In the study, Dr Hermes and colleagues stimulated pairs of electrodes with a brief electrical pulse to measure the time it took signals to travel among brain regions in 74 research participants between the ages of 4 and 51. The intracranial measurements were done in a small population of patients who had electrodes implanted for epilepsy monitoring at University Medical Center Utrecht, Netherlands.

The response delays in connected brain regions showed that transmission speeds in the human brain increase throughout childhood and even into early adulthood. They plateau around 30 to 40 years of age.

The team’s data indicate that adult transmission speeds were about two times faster compared to those typically found in children. Transmission speeds also were typically faster in 30- or 40-year-old subjects compared to teenagers.

Brain transmission speed is measured in milliseconds, a unit of time equal to one-thousandth of a second. For example, the researchers measured the neuronal speed of a 4-year-old patient at 45 milliseconds for a signal to travel from the frontal to parietal regions of the brain. In a 38-year-old patient, the same pathway was measured at 20 milliseconds. For comparison, the blink of an eye takes about 100 to 400 milliseconds.

The researchers are working to characterise electrical stimulation-driven connectivity in the human brain. One of the next steps is to better understand how transmission speeds change with neurological diseases. They are collaborating with paediatric neurosurgeons and neurologists to understand how diseases change transmission speeds compared to what would be considered within the normal range for a certain age group.

Source: Mayo Clinic

Functional MRI is Now Able to Read People’s Minds

Photo by Mart Production on Pexels

In a study in Nature, researchers reported being able to identify words and phrases in volunteers undergoing fMRI imaging reasonable accuracy. The process is non-invasive, unlike implanted electrodes, but requires hours of preparation and scanning.

This technology would be a significant breakthrough for people suffering debilitating conditions that prevent them from speaking or otherwise communicating. Previously, decoding language required the use of extensive electrode implants.

The participants, two male and one female, listened to recordings of radio shows. This was used to train a language model which was based on an early version of ChatGPT. By looking at the brain’s responses, the language model was able to capture the gist of what the participants were thinking, sometimes replicating exact words or entire phrases.

Marked safe from ‘Big Brother’… for now

At this stage, the technology used requires the subject to cooperate, the researchers wrote, allaying concerns over any malicious use of this technology to tap into people’s private thoughts. Testing the decoding model on people who it hadn’t been trained on produced unintelligible results, as was the case when the trained participants put up resistance.

While the technology cannot be used for nefarious mind-reading, the march of progress means that one day such concerns will become real.

Nita Farahany, JD, PhD, of Duke University in Durham, North Carolina, told MedPage Today that the technology could one day be used against people. “This research illustrates the rapid advances being made toward an age of much greater brain transparency, where even continuous language and semantic meaning can be decoded from the brain.

“While people can employ effective countermeasures to prevent decoding their brains using fMRI, as brain wearables become widespread that may not be an effective way to protect us from interception, manipulation, or even punishment for our thoughts.”

While lugging around a massive MRI machine would be a challenge for future thought police, smaller, more portable means of measuring brain activity remotely. Senior author Alexander Huth, PhD, of the University of Texas at Austin, says that one such technology could be functional near-infrared spectroscopy (fNIRS).

“fNIRS measures where there’s more or less blood flow in the brain at different points in time, which, it turns out, is exactly the same kind of signal that fMRI is measuring,” Huth said. “So, our exact kind of approach should translate to fNIRS,” but the resolution with fNIRS would be lower.

How Psychedelics Alter Brain Activity to Produce ‘Trips’

In a study published in the journal PNAS, detailed brain imaging data from 20 healthy volunteers revealed how the potent psychedelic compound, DMT (dimethyltryptamine), alters brain function. During the immersive DMT experience, there was increased connectivity across the brain, with more communication between different areas and systems. The changes to brain activity were most prominent in areas linked with ‘higher level’ functions, such as imagination.

DMT is a potent psychedelic found naturally in certain plants and animals, and unlike classic psychedelics, such as LSD or psilocybin, DMT’s has shorter-lasting effects on the brain, measured in minutes, rather than hours. It occurs in trace amounts in the human body and is the major psychoactive compound in ayahuasca.

The study is the first to track brain activity before, during and after the DMT experience in such detail.

Dr Chris Timmerman, from the Centre for Psychedelic Research at Imperial College London, and first author on the study, said: “This work is exciting as it provides the most advanced human neuroimaging view of the psychedelic state to-date.

“One increasingly popular view is that much of brain function is concerned with modelling or predicting its environment. Humans have unusually big brains and model an unusually large amount of the world. For example, like with optical illusions, when we’re looking at something, some of what we’re actually seeing is our brain filling in the blanks based on what we already know. What we have seen with DMT is that activity in highly evolved areas and systems of the brain that encode especially high-level models becomes highly dysregulated under the drug, and this relates to the intense drug ‘trip’.”

DMT can produce intense and immersive altered states of consciousness, with the experience characterised by vivid and bizarre visions, a sense of ‘visiting’ alternative realities or dimensions, and similarities with near death experiences. But exactly how the compound alters brain function to account for such effects has been unclear.

In the latest study, 20 healthy volunteers were given an injection of the drug while researchers from Imperial’s Centre for Psychedelic Research captured detailed imagery of their brains, enabling the team to study how activity changes before, during and after the trip.

Volunteers intravenously received a high dose of DMT (20mg), while simultaneously undergoing functional magnetic resonance imaging (fMRI) of their brain and electroencephalography (EEG). The total psychedelic experience lasted about 20 minutes, and at regular intervals, volunteers provided a rating of the subjective intensity of their experience (on a 1 to 10 scale).

The fMRI scans found changes to activity within and between brain regions in volunteers under the influence of DMT. Effects included increased connectivity across the brain, with more communication between different areas and systems. These phenomena, termed ‘network disintegration and desegregation’ and increased ‘global functional connectivity’, align with previous studies with other psychedelics. The changes to activity were most prominent in brain areas linked with ‘higher level’, human-specific functions, such as imagination.

The researchers highlight that while their study is not the first to image the brain under the influence of psychedelics or the first to show the signatures of brain activity linked to psychedelics, it is the first to combine imaging techniques to study the brain during a highly immersive psychedelic experience. They explain the work provides further evidence of how DMT, and psychedelics more generally, exert their effects by disrupting high level brain systems.

Prof Robin Carhart-Harris, founder of the Centre for Psychedelic Research at Imperial College London, and senior author on the paper (now working at the University of California, San Francisco), commented: “Motivated by, and building on our previous research with psychedelics, the present work combined two complementary methods for imaging the brain imaging. fMRI allowed us to see the whole of the brain, including its deepest structures, and EEG helped us view the brain’s fine-grained rhythmic activity.

“Our results revealed that when a volunteer was on DMT there was a marked dysregulation of some of the brain rhythms that would ordinarily be dominant. The brain switched in its mode of functioning to something altogether more anarchic. It will be fascinating to follow-up on these insights in the years to come. Psychedelics are proving to be extremely powerful scientific tools for furthering our understanding of how brain activity relates to conscious experience.”

The Imperial team is now exploring how to prolong the peak of the psychedelic experience through continuous infusion with DMT, and some are also advising on a commercially run trial to assess DMT for patients with depression.

Source: Imperial College London

Up to Half of Concussions May Have Long-lasting Effects

Photo by Tom Jur on Unsplash

Even mild concussion can cause long-lasting effects to the brain, according to a University of Cambridge analysis published in Brain. The study researchers showed that for almost a half of all people who receive a concussion, there are changes in how regions of the brain communicate with each other. This could potential cause long term symptoms such as fatigue and cognitive impairment.

Concussion, a mild traumatic brain injury, can occur as a result of a fall, a sports injury or from a cycling accident or car crash, for example. But despite the ‘mild’ label, it is commonly linked with persistent symptoms and incomplete recovery. Such symptoms include depression, cognitive impairment, headaches, and fatigue.

While some clinicians in recent studies predict that 9 out of 10 individuals who experience concussion will have a full recovery after six months, evidence is emerging that only a half achieve a full recovery. This means that a significant proportion of patients may not receive adequate post-injury care.

Predicting which patients will have a fast recovery and who will take longer to recover is challenging, however. At present, patients with suspected concussion will typically receive either a CT or MRI brain scan to look for structural problems, such as inflammation or bruising. Yet even if these scans show no obvious structural damage, a patient’s symptoms may still persist.

Dr Emmanuel Stamatakis from the Department of Clinical Neurosciences and Division of Anaesthesia at the University of Cambridge said: “Worldwide, we’re seeing an increase in the number of cases of mild traumatic brain injury, particularly from falls in our ageing population and rising numbers of road traffic collisions in low- and middle-income countries.

“At present, we have no clear way of working out which of these patients will have a speedy recovery and which will take longer, and the combination of over-optimistic and imprecise prognoses means that some patients risk not receiving adequate care for their symptoms.”

Dr Stamatakis and colleagues studied functional MRI (fMRI) brain scans taken from 108 patients with mild traumatic brain injury and compared them with scans from 76 healthy volunteers. Patients were also assessed for ongoing symptoms.

The patients and volunteers had been recruited to CENTER-TBI, a large European research project which aims to improve the care for patients with traumatic brain injury.

The team found that just under half (45%) were still showing symptoms resulting from their brain injury, with the most common being fatigue, poor concentration and headaches.

The researchers found that these patients had abnormalities in a region of the brain known as the thalamus, which integrates all sensory information and relays this information around the brain. Counter-intuitively, concussion was associated with increased connectivity between the thalamus and the rest of the brain – in other words, the thalamus was trying to communicate more as a result of the injury – and the greater this connectivity, the poorer the prognosis for the patient.

Rebecca Woodrow, a PhD student in the Department of Clinical Neuroscience and Hughes Hall, Cambridge, said: “Despite there being no obvious structural damage to the brain in routine scans, we saw clear evidence that the thalamus – the brain’s relay system – was hyperconnected. We might interpret this as the thalamus trying to over-compensate for any anticipated damage, and this appears to be at the root of some of the long-lasting symptoms that patients experience.”

Using positron emission tomography (PET) scans, the researchers were able to make associations with key neurotransmitters depending on which long-term symptoms a patient displayed. For example, patients experiencing cognitive problems such as memory difficulties showed increased connectivity between the thalamus and areas of the brain rich in the neurotransmitter noradrenaline; patients experiencing emotional symptoms, such as depression or irritability, showed greater connectivity with areas of the brain rich in serotonin.

Dr Stamatakis added: “We know that there already drugs that target these brain chemicals so our findings offer hope that in future, not only might we be able to predict a patient’s prognosis, but we may also be able to offer a treatment targeting their particular symptoms.”

Source: University of Cambridge

Introducing The Wits Journal of Neuroscience – Inaugural Issue

Modern Media Publishing is pleased to announce the inaugural issue of the Wits Journal of Neuroscience*, a new academic journal aiming to connect those in the field of neuroscience and broaden its horizons in South Africa.

The journal is available online here, and will also have a print distribution.

The new publication will feature articles from clinician researchers in the fields of neurosurgery, neurology, ophthalmology and ears, nose and throat (ENT). The journal features original research and case reports and MMed articles selected by its distinguished editorial board. It also reports on local neuroscience news and events as well as international research highlights. Readers also get a peek behind the curtain at upcoming research.

Professor John R. Ouma, Head of Department of Neuroscience at Wits said, “The aim of this new journal is to fill a gap that has been existing, wherein there has not hitherto been a common platform for academicians and others interested in neurosciences to come together and share ideas as well as generate new science.

“This journal will be widely circulated within the Neuroscience community of this University and its associated hospitals, and then further afield to sister Universities, hospitals and entities to ensure that the ideas generated and expressed in it achieve the widest exposure and impact.

“We hope you enjoy it, both now, and in future editions.”

*The Wits Journal of Neuroscience is Produced and Distributed on behalf of the Wits Dept of Neuroscience by Modern Media Publishing (Pty) Ltd. They can be contacted on 011-326-4171 or by email on info@modernmedia.co.za

Improper ‘Pruning’ of Brain Connections may Cause Teen Mental Health Disorders

Photo by Andrew Neel on Unsplash

Problems with the brain’s ability to ‘prune’ itself of unnecessary connections may underlie a wide range of mental health disorders that begin during adolescence, according to research published in Nature Medicine.

The findings, from an international collaboration, led by researchers in the UK, China and Germany, may help explain why people are often affected by more than one mental health disorder, and may in future help identify those at greatest risk.

One in seven adolescents (aged 10-19 years old) worldwide experiences mental health disorders, according to the World Health Organization (WHO). Depression, anxiety and behavioural disorders, such as attention deficit hyperactivity disorder (ADHD), are among the leading causes of illness and disability among young people, and adolescents will commonly have more than one mental health disorder.

Many mental health problems emerge during adolescence, such as depression and anxiety, which manifest as ‘internalising’ symptoms, including low mood and worrying. Other conditions such as attention deficit hyperactivity disorder (ADHD) manifest as ‘externalising’ symptoms, such as impulsive behaviour.

Professor Barbara Sahakian from the Department of Psychiatry at the University of Cambridge said: “Young people often experience multiple mental health disorders, beginning in adolescence and continuing – and often transforming – into adult life. This suggests that there’s a common brain mechanism that could explain the onset of these mental health disorders during this critical time of brain development.”

In the study, the researchers say they have identified a characteristic pattern of brain activity among these adolescents, which they have termed the ‘neuropsychopathological factor’, or NP factor for short.

The team examined data from 1,750 adolescents, aged 14 years, from the IMAGEN cohort, a European research project examining how biological, psychological, and environmental factors during adolescence may influence brain development and mental health. In particular, they examined imaging data from brain scans taken while participants took part in cognitive tasks, looking for patterns of brain connectivity – in other words, how different regions of the brain communicate with each other.

Adolescents who experienced mental health problems – regardless of whether their disorder was one of internalising or externalising symptoms, or whether they experienced multiple disorders – showed similar patterns of brain activity. These patterns – the NP factor – were largely apparent in the frontal lobes, the area at the front of the brain responsible for executive function which, among other functions, controls flexible thinking, self-control and emotional behaviour.

The researchers confirmed their findings by replicating them in 1799 participants from the ABCD Study in the USA, a long-term study of brain development and child health, and by studying patients who had received psychiatric diagnoses.

When the team looked at genetic data from the IMAGEN cohort, they found that the NP factor was strongest in individuals who carried a particular variant of the gene IGSF11 that has been previously associated with multiple mental health disorders. This gene is known to play an important role in synaptic pruning, a process whereby unnecessary brain connections – synapses – are discarded. Problems with pruning may particularly affect the frontal lobes, since these regions are the last brain areas to complete development in adolescents and young adults.

Dr Tianye Jia from the Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China and the Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK said: “As we grow up, our brains make more and more connections. This is a normal part of our development. But too many connections risk making the brain inefficient. Synaptic pruning helps ensure that brain activity doesn’t get drowned out in ‘white noise’.

“Our research suggests that when this important pruning process is disrupted, it affects how brain regions talk to each other. As this impact is seen most in the frontal lobes, this then has implications for mental health.”

The researchers say that the discovery of the NP factor could help identify those young people at greatest risk of compounding mental health problems.

Professor Jianfeng Feng from Fudan University in Shanghai, China, and the University of Warwick, UK, said: “We know that many mental health disorders begin in adolescence and that individuals who develop one disorder are at increased risk of developing other disorders, too. By examining brain activity and looking for this NP factor, we might be able to detect those at greatest risk sooner, offering us more opportunity to intervene and reduce this risk.”

Source: University of Cambridge

Evidence of Deep Connection Between Body and Mind

Source: CC0

A new study suggests that notion of the body and mind being inextricably intertwined is more than mere abstraction: parts of the brain area that control movement are plugged into networks involved in thinking and planning, and in control of involuntary bodily functions such as blood pressure and heartbeat. The findings represent a literal linkage of body and mind in the very structure of the brain, overturning decades of interpretations.

The research, published in the journal Nature, could help explain some baffling phenomena, such as why anxiety causes people to pace; why stimulating the vagus nerve, which regulates internal organ functions such as digestion and heart rate, may alleviate depression; and why people who exercise regularly report a more positive outlook on life.

“People who meditate say that by calming your body with, say, breathing exercises, you also calm your mind,” said first author Evan M. Gordon, PhD, an assistant professor of radiology at Washington University School of Medicine in St. Louis. “Those sorts of practices can be really helpful for people with anxiety, for example, but so far, there hasn’t been much scientific evidence for how it works. But now we’ve found a connection. We’ve found the place where the highly active, goal-oriented ‘go, go, go’ part of your mind connects to the parts of the brain that control breathing and heart rate. If you calm one down, it absolutely should have feedback effects on the other.”

Gordon and senior author Nico Dosenbach, MD, PhD, an associate professor of neurology, did not set out to answer age-old philosophical questions about the relationship between the body and the mind. They set out to verify the long-established map of the areas of the brain that control movement, using modern brain-imaging techniques.

In the 1930s, neurosurgeon Wilder Penfield, MD, mapped such motor areas of the brain by applying small jolts of electricity to the exposed brains of people undergoing brain surgery, and noting their responses. He discovered that stimulating a narrow strip of tissue on each half of the brain causes specific body parts to twitch. Moreover, the control areas in the brain are arranged in the same order as the body parts they direct, with the toes at one end of each strip and the face at the other. Penfield’s map of the motor regions of the brain – depicted as a homunculus, or “little man” – has become a staple of neuroscience textbooks.

Gordon, Dosenbach and colleagues set about replicating Penfield’s work with functional magnetic resonance imaging (fMRI). They recruited seven healthy adults to undergo hours of fMRI brain scanning while resting or performing tasks. From this high-density dataset, they built individualized brain maps for each participant. Then, they validated their results using three large, publicly available fMRI datasets – the Human Connectome Project, the Adolescent Brain Cognitive Development Study and the UK Biobank – which together contain brain scans from about 50 000 people.

To their surprise, they discovered that Penfield’s map wasn’t quite right. Control of the feet was in the spot Penfield had identified. Same for the hands and the face. But interspersed with those three key areas were another three areas that did not seem to be directly involved in movement at all, even though they lay in the brain’s motor area.

Moreover, the nonmovement areas looked different than the movement areas. They appeared thinner and were strongly connected to each other and to other parts of the brain involved in thinking, planning, mental arousal, pain, and control of internal organs and functions such as blood pressure and heart rate. Further imaging experiments showed that while the nonmovement areas did not become active during movement, they did become active when the person thought about moving.

“All of these connections make sense if you think about what the brain is really for,” Dosenbach said. “The brain is for successfully behaving in the environment so you can achieve your goals without hurting or killing yourself. You move your body for a reason. Of course, the motor areas must be connected to executive function and control of basic bodily processes, like blood pressure and pain. Pain is the most powerful feedback, right? You do something, and it hurts, and you think, ‘I’m not doing that again.'”

Dosenbach and Gordon named their newly identified network the Somato (body)-Cognitive (mind) Action Network, or SCAN. To understand how the network developed and evolved, they scanned the brains of a newborn, a 1-year-old and a 9-year-old. They also analysed data that had been previously collected on 9 monkeys. The network was not detectable in the newborn, but it was clearly evident in the 1-year-old and nearly adult-like in the 9-year-old. The monkeys had a smaller, more rudimentary system without the extensive connections seen in humans.

“This may have started as a simpler system to integrate movement with physiology so that we don’t pass out, for example, when we stand up,” Gordon said. “But as we evolved into organisms that do much more complex thinking and planning, the system has been upgraded to plug in a lot of very complex cognitive elements.”

Clues to the existence of a mind-body network have been around for a long time, scattered in isolated papers and inexplicable observations.

“Penfield was brilliant, and his ideas have been dominant for 90 years, and it created a blind spot in the field,” said Dosenbach, who is also an associate professor of biomedical engineering, of paediatrics, occupational therapy, radiology, and psychological & brain sciences. “Once we started looking for it, we found lots of published data that didn’t quite jibe with his ideas, and alternative interpretations that had been ignored. We pulled together a lot of different data in addition to our own observations, and zoomed out and synthesised it, and came up with a new way of thinking about how the body and the mind are tied together.”

Source: Washington University School of Medicine

Neurons in Developing Brains are Connected by Nanoscopic Tunnels

Example of 3D imaging of segmented granule cells shown in green and orange, with nuclei in blue and purple respectively, and mitochondria in yellow. A thin connection can be seen between the two cells in blue, with subcompartments attached to the tube containing the mitochondria, shown in pink. Credit: Diego Cordero / Membrane Traffic and Pathogenesis Unit, Institut Pasteur

Over a hundred years after the discovery of the neuron by neuroanatomist Santiago Ramón y Cajal, scientists continue to deepen their knowledge of the brain and its development. Now, scientists detail novel insights into how cells in the outer layers of the brain interact immediately after birth during formation of the cerebellum, the brain region towards the back of the skull. Publishing their results in in Science Advances, the scientists demonstrated a novel type of connection between neural precursor cells via nanotubes, even before synapses form.

In 2009, Chiara Zurzolo’s team from the Institut Pasteur identified a novel mechanism for direct communication between neuronal cells in culture via nanoscopic tunnels, known as tunnelling nanotubes. These are involved in the spread of various toxic proteins that accumulate in the brain during neurodegenerative diseases – but may also be tapped for the treatment of diseases or cancers.

In this new study, the researchers discovered nanoscopic tunnels that connect precursor cells in the brain, more specifically the cerebellum – an area that develops after birth and is important for making postural adjustments to maintain balance – as they mature into neurons. These tunnels, although similar in size, vary in shape from one to another: some contain branches while others don’t, some are enveloped by the cells they connect while others are exposed to their local environment. The authors believe these intercellular connections (ICs) may enable the exchange of molecules that help pre-neuronal cells physically migrate across various layers and reach their final destination as the brain develops.

Intriguingly, ICs share anatomical similarities with bridges formed when cells finish dividing. “ICs could derive from cellular division but persist during cell migration, so this study could shed light on the mechanisms allowing coordination between cell division and migration implicated in brain development. On the other hand, ICs established between cells post mitotically could allow direct exchange between cells beyond the usual synaptic connections, representing a revolution in our understanding of brain connectivity. We show that there are not only synapses allowing communication between cells in the brain, there are also nanotubes,” says Dr Zurzolo, senior author and head of the Membrane Traffic and Pathogenesis Unit (Institut Pasteur/CNRS).

To achieve these discoveries, the researchers used a three-dimensional (3D) electron microscopy method and brain cells from mouse models to study how the brain regions communicate between each other. Very high resolution neural network maps could thus be reconstructed. The 3D cerebellum volume produced and used for the study contains over 2000 cells. “If you really want to understand how cells behave in a three-dimensional environment, and map the location and distribution of these tunnels, you have to reconstruct an entire ecosystem of the brain, which requires extraordinary effort with twenty or so people involved over 4 years,” said the article’s first author Diego Cordero.

To meet the challenges of working with the wide range of cell types the brain contains, the authors used an AI tool to automatically distinguish cortical layers. Furthermore, they developed an open-source program called CellWalker to characterise morphological features of 3D segments. The tissue block was reconstructed from brain section images. This program being made freely available will enable scientists to quickly and easily analyse the complex anatomical information embedded in these types of microscope images.

The next step will be to identify the biological function of these cellular tunnels to understand their role in the development of the central nervous system and in other brain regions, and their function in communication between brain cells in neurodegenerative diseases and cancers.

Source: Institut Pasteur

Dopamine’s Role in Exercise Feeling ‘Hard’ or ‘Easy’

Photo by Jonathan Borba on Unsplash

Dopamine, long associated with pleasure, motivation and reward-seeking, also appears to play an important role in why exercise and other physical efforts feel ‘easy’ to some people and exhausting to others. These are the findings of of a study of people with Parkinson’s disease, which is published in NPG Parkinson’s Disease. Parkinson’s disease is marked by a loss of dopamine-producing cells in the brain over time.

According to the researchers, the findings might eventually lead to more effective ways to help people establish and stick with exercise regimens, new treatments for fatigue associated with depression and many other conditions, and a better understanding of Parkinson’s disease.

“Researchers have long been trying to understand why some people find physical effort easier than others,” says study leader Vikram Chib, Ph.D., associate professor in the Department of Biomedical Engineering at the Johns Hopkins University School of Medicine and research scientist at the Kennedy Krieger Institute. “This study’s results suggest that the amount of dopamine availability in the brain is a key factor.”

Chib explains that after a bout of physical activity, people’s perception and self-reports of the effort they expended varies, and also guides their decisions about undertaking future exertions. Previous studies have shown that people with increased dopamine are more willing to exert physical effort for rewards, but the current study focuses on dopamine’s role in people’s self-assessment of effort needed for a physical task, without the promise of a reward.

For the study, Chib and his colleagues from Johns Hopkins Medicine and the Kennedy Krieger Institute recruited 19 adults diagnosed with Parkinson’s disease, a condition in which neurons in the brain that produce dopamine gradually die off, causing unintended and uncontrollable movements such as tremors, fatigue, stiffness and trouble with balance or coordination.

In Chib’s lab, 10 male volunteers and nine female volunteers with an average age of 67 were asked to perform the same physical task, that of squeezing a hand grip equipped with a sensor, on two different days within four weeks of each other. On one of the days, the patients were asked to take their standard, daily synthetic dopamine medication as they normally would. On the other, they were asked not to take their medication for at least 12 hours prior to performing the squeeze test.

On both days, the patients were initially taught to squeeze a grip sensor at various levels of defined effort, and then were asked to squeeze and report how many units of effort they put forth.

When the participants had taken their regular synthetic dopamine medication, their self-assessments of units of effort expended were more accurate than when they hadn’t taken the drug. They also had less variability in their efforts, showing accurate squeezes when the researchers cued them to squeeze at different levels of effort.

In contrast, when the patients hadn’t taken the medication, they consistently over-reported their efforts, meaning they perceived the task to be physically harder, and had significantly more variability among grips after being cued.

In another experiment, the patients were given a choice between a sure option of squeezing with a relatively low amount of effort on the grip sensor or flipping a coin and taking a chance on having to perform either no effort or a very high level of effort. When these volunteers had taken their medication, they were more willing to take a chance on having to perform a higher amount of effort than when they didn’t take their medication.

A third experiment offered participants the choice between getting a small amount of guaranteed money or, getting either nothing or a higher amount of money on a coin flip. Results showed no difference in the subjects on days when they took their medication and when they did not. This result, researchers say, suggests that dopamine’s influence on risk-taking preferences is specific to physical effort-based decision-making.

Together, Chib says, these findings suggest that dopamine level is a critical factor in helping people accurately assess how much effort a physical task requires, which can significantly affect how much effort they’re willing to put forth for future tasks. For example, if someone perceives that a physical task will take an extraordinary amount of effort, they may be less motivated to do it.

Understanding more about the chemistry and biology of motivation could advance ways to motivate exercise and physical therapy regimens, Chib says. In addition, inefficient dopamine signalling could help explain the pervasive fatigue present in conditions such as depression and long COVID, and during cancer treatments. Currently, he and his colleagues are studying dopamine’s role in clinical fatigue.

Source: John Hopkins Medicine

Researchers Identify a Protein to Treat Intracerebral Haemorrhage

Photo by cottonbro studio from Pexels

University of Helsinki and Taiwanese researchers have found a new way to remove waste from the brain after haemorrhage, using a protein called cerebral dopamine neurotrophic factor (CDNF).

Intracerebral haemorrhage, and bleeding into the brain tissue, is a devastating neurological condition affecting millions of people annually. It has a high mortality rate, with long-term neurological deficits experienced by many survivors. To date, no medication has been identified that supports brain recovery following haemorrhage.

In an international collaboration, researchers from the Brain Repair laboratory, University of Helsinki, together with their Taiwanese colleagues investigated whether CDNF, a protein being currently tested for Parkinson’s disease treatment, could be a potential treatment for brain haemorrhage.

Research suggests that CDBF also has therapeutic effects and enhances immune cell’s response after brain haemorrhage. The authors found that the administration of cerebral dopamine neurotrophic factor accelerates haemorrhagic lesion resolution, reduces brain swelling, and improves functional outcomes in an animal model of brain haemorrhage.

“Surprisingly, we found that cerebral dopamine neurotrophic factor acts on immune cells in the bleeding brain, by increasing anti-inflammatory mediators and suppressing the production of the pro-inflammatory cytokines that are responsible for cell signalling. This is a significant step towards the treatment of injuries caused by brain haemorrhage, for which we currently have no cure,” says Professor Mikko Airavaara, from University of Helsinki.

Dr.Vassileios Stratoulias from the Brain Repair laboratory comments, “It’s interesting to note that after a bleeding episode, the brain contains a lot of waste and debris. Cerebral dopamine neurotrophic factor encourages immune cells in the brain to consume and remove the waste and debris, which is essential for the brain’s recovery!.”

The administration of cerebral dopamine neurotrophic factor also resulted in the alleviation of cell stress in the area that surrounds the haematoma.

Finally, the researchers demonstrated that systemic administration of cerebral dopamine neurotrophic factor promotes scavenging by the brain’s immune cells after brain haemorrhage and has beneficial effects in an animal model of brain haemorrhage.

Source: University of Helsinki