Parkinson's: New hope when treatment options seem exhausted

Prof. Paul Lingor
Photo Credit: Courtesy of Technical University of Munich

As Parkinson's progresses, more invasive therapies are used that require brain surgery, for example. When these no longer deliver the desired results, physicians often conclude that treatment options are exhausted. A study led by researchers at the Technical University of Munich (TUM) now shows that such patients can still benefit from a change in treatment. So far, however, this option has only been used very rarely.

A team led by Prof. Paul Lingor has examined data from 22 German Parkinson's centers. The result: although there are several options for therapies in the late stages of the disease, rarely is more than one used - although those affected often benefit from them.

Parkinson's disease is the world’s second-most common neurodegenerative disease after Alzheimer's. So far it has proved incurable. Only the symptoms can be treated. In the early stages, tablets can generally provide relief from complaints. As the disease progresses, this is often no longer enough.

Molecular blueprint of circuits governing locomotor speed

Zebra fish
Photo Credit: Lars Bräutigam

Researchers at Karolinska Institutet, Sweden have uncovered the molecular logic underpinning the assembly of spinal circuits that control the speed of locomotion in adult zebrafish. The study has recently been published in Nature Neuroscience.

What does the study show?

A fundamental hallmark of motor actions is the flexibility of their timing, speed and strength that is central to rapid adaptation to the ever-changing world around us. This is particularly apparent during locomotion, a behavior that involves full-body coordination characterized by sudden changes in speed and strength.

“In this study, we used single-cell RNA sequencing in adult zebrafish to link the molecular diversity of motoneurons and interneurons with their modular circuit organization that is responsible for changes in locomotor speed” says Abdel El Manira, Professor at the Department of Neuroscience at Karolinska Institutet, and corresponding author of the article.

Brain health in over 50s deteriorated more rapidly during the pandemic

Photo Credit: Gabriel Porras

Brain health in over 50s deteriorated more rapidly during the pandemic, even if they didn’t have COVID-19, according to major new research linking the pandemic to sustained cognitive decline.

Researchers looked at results from computerized brain function tests from more than 3,000 participants of the online PROTECT study, who were aged between 50 and 90 and based in the UK. The remote study, led by teams at the University of Exeter and the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London, and part-funded by NIHR Maudsley BRC, tested participants’ short-term memory and ability to complete complex tasks.

Through analyzing the results from this big dataset, researchers found that cognitive decline quickened significantly in the first year of the pandemic, when they found a 50 per cent change to the rate of decline across the study group. This figure was higher in those who already had mild cognitive decline before the pandemic, according to the research published in The Lancet Healthy Longevity.

What Happens When We Pass Out? Researchers ID New Brain and Heart Connections

An image of a heart labeled by vagal sensory neurons. In a new study published in the journal Nature, UC San Diego researchers and their colleagues found that these neurons trigger fainting, laying a foundation for addressing fainting-related disorders.
Image Credit: Augustine Lab, UC San Diego

Nearly 40 percent of people experience syncope, or fainting spells, at least once in their lives. These brief losses of consciousness, whether brought by pain, fear, heat, hyperventilation or other causes, account for a significant portion of hospital emergency room visits. Yet the exact root mechanisms at play when people “pass out” largely have remained a mystery.

Publishing a new report in Nature, University of California San Diego researchers, along with colleagues at The Scripps Research Institute and other institutions, have for the first time identified the genetic pathway between the heart and brain tied to fainting.

One of their unique approaches was to think of the heart as a sensory organ rather than the longstanding viewpoint that the brain sends out signals and the heart simply follows directions. School of Biological Sciences Assistant Professor Vineet Augustine, the paper’s senior author, applies a variety of approaches to better understand these neural connections between the heart and brain.

High metabolism is an early sign of Alzheimer’s disease

Illustration Credit: geralt

An early phase in the process of developing Alzheimer’s disease is a metabolic increase in a part of the brain called the hippocampus, report researchers from Karolinska Institutet in a study published in Molecular Psychiatry. The discovery opens up new potential methods of early intervention.

Alzheimer’s disease is the most common form of dementia and strikes about 20,000 people in Sweden every year. Researchers now show that a metabolic increase in the mitochondria, the cellular power plants, is an early indicator of the disease. 

The teams behind the study used mice that developed Alzheimer’s disease pathology in a similar way to humans. The increase in metabolism in young mice was followed by synaptic changes caused by disruption to the cellular recycling system (a process known as autophagy), a finding that was awarded the Nobel Prize in Physiology or Medicine in 2016. 

After a time, metabolism in the Alzheimer brain usually declines, which contributes to the degradation of synapses. This the researchers could also see in the older mice, which had had the disease for a longer time. 

Sets of neurons work in sync to track ‘time’ and ‘place,’ giving humans context for past, present and future

Illustration Credit: MasterTux

Two studies led by UCLA researchers offer new insights into the way neurons in the human brain represent time and space – the most basic ingredients of consciousness of human existence and the primary dimensions of experience that allow us to reconstruct the past and envision the future.

The new findings are based on recordings of the activity of single neurons in the brain, from studies led by Dr. Itzhak Fried, a neurosurgeon and researcher at the UCLA David Geffen School of Medicine, is the senior author of two articles in Cell Reports. Patients who had undergone surgical placement of special depth electrodes developed and implanted by Fried for surgical treatment of intractable epilepsy agreed to perform cognitive tasks while their brain cell activity is recorded for these studies.

Neurons that act as the brain’s GPS system – termed “place cells” and “grid cells” – were discovered initially in rodents, similar findings later described in humans by Fried and colleagues at UCLA in collaboration with Dr. Michael Kahana, professor of Psychology at the University of Pennsylvania and a co-senior author of one of the new studies. The brain’s clock cells, or “time cells,” were identified in more recent years.

New genes linked to ADHD identified potentially paving the way for new treatments

Image Credit: Braňo

Several new genes associated with conditions such as Attention-deficit hyperactivity disorder (ADHD) have been identified, unearthing a significant connection between these disorders and our immune system that could lead to new treatments. The research from the University of Surrey also confirms the role of gene ADGRL3 in conditions such as ADHD, giving scientists a greater understanding of its workings.

During this innovative study, scientists led by Dr Matt Parker from Surrey set out to understand more about ADGRL3, a gene closely linked to ADHD and other ‘externalizing’ disorders, in promoting behaviors such as substance abuse, which can be associated with the conditions. Through this work, scientists identified several new genes related to externalizing disorders, which could lead to the development of new medication to lessen the impact on individuals.

DNA organization influences the growth of deadly brain tumors in response to neuronal signals

Silvia Remeseiro
Photo Credit: Mattias Pettersson

A pioneering study at Umeå University, Sweden, has unveiled that the 3D organization of DNA can influence the progression of the aggressive brain tumor known as glioblastoma. Having identified the factors that glioblastoma uses to respond to neurons by growing and spreading, this discovery paves the way for further research into new treatments for brain tumors.

"We have now identified the most important factors behind how the tumor responds to nerve cells, thus becoming more dangerous. These findings offer hope in our long-term battle against this difficult-to-treat cancer, for which the prognosis has not improved in decades," comments Silvia Remeseiro, Wallenberg fellow at WCMM, Assistant Professor at Umeå University, and lead author of the study.

Glioblastoma is the most fatal type of brain tumor among adults and there is currently no curative treatment. Glioblastoma patients typically face a survival of roughly one-year post-diagnosis. Even following current treatment regimes, which include surgery, radiotherapy and chemotherapy, a mere four per cent of patients are still alive five years after diagnosis.

The brain may learn about the world the same way some computational models do

Two new MIT studies offer evidence supporting the idea that the brain uses a process similar to a machine-learning approach known as “self-supervised learning.”
Illustration Credit: geralt

To make our way through the world, our brain must develop an intuitive understanding of the physical world around us, which we then use to interpret sensory information coming into the brain.

How does the brain develop that intuitive understanding? Many scientists believe that it may use a process similar to what’s known as “self-supervised learning.” This type of machine learning, originally developed as a way to create more efficient models for computer vision, allows computational models to learn about visual scenes based solely on the similarities and differences between them, with no labels or other information.

A pair of studies from researchers at the K. Lisa Yang Integrative Computational Neuroscience (ICoN) Center at MIT offers new evidence supporting this hypothesis. The researchers found that when they trained models known as neural networks using a particular type of self-supervised learning, the resulting models generated activity patterns very similar to those seen in the brains of animals that were performing the same tasks as the models.

The findings suggest that these models are able to learn representations of the physical world that they can use to make accurate predictions about what will happen in that world, and that the mammalian brain may be using the same strategy, the researchers say.

An unexpected link between 2 schizophrenia risk proteins

The study findings suggest that when the proteins don’t bind properly, signaling among neurons, illustrated above, becomes imbalanced, which can lead to related negative behavioral symptoms.
 Image Credit: T. Ahmed, A. Buonanno, National institute of Child Health and Human Development

The discovery of a physical interaction between two proteins in brain cells that can be traced in mice to control of movement, anxiety and memory could one day open the door to development of new schizophrenia treatment strategies.

The research group is the first to determine that the two proteins, both among the dozens of proteins related to risk for the development of schizophrenia, bind to each other under normal conditions in multiple regions of the brain, and that their connection was found in mice to be key to maintaining normal movement, memory function and anxiety regulation.

When that connection doesn’t happen as it should, they found, behavior can be negatively affected – in mice, disruption to the proteins’ ability to interact increased hyperactivity, reduced risk avoidance and impaired memory. Though delusions and hallucinations are hallmark symptoms of schizophrenia, the condition also encompasses additional symptoms, including movement and memory problems. 

“These two proteins are seemingly unrelated, and our study has provided a link between them that wasn’t recognized before,” said lead author Chen Gu, associate professor of biological chemistry and pharmacology in The Ohio State University College of Medicine.  

First digital atlas of human fetal brain development published

Image Credit: Geralt

The first digital atlas showing how the human brain develops in the womb has been published by a global research team led by the University of Oxford.

A team of over 200 researchers around the world, involving multiple health and scientific institutions, led by the University of Oxford, has today published, in the journal Nature, the first digital atlas showing the dynamics of normative maturation of each hemisphere of the fetal brain between 14- and 31-weeks’ gestation - a critical period of human development.

The atlas was produced using over 2,500 3-dimensional ultrasound (3D US) brain scans that were acquired serially during pregnancy from 2,194 fetuses in the INTERGROWTH-21st Project, which is a large population-based study of healthy pregnant women living in eight diverse geographical regions of the world (including five in the Global South), whose children had satisfactory growth and neurodevelopment at 2 years of age.

The study is unique because, for the first time, an international dataset of 3D US scans, collected using standardized methods and equipment, has been analyzed with advanced artificial intelligence (AI) and image processing tools to construct a map showing how the fetal brain matures as pregnancy advances.

Brain implant at OHSU successfully controls both seizures and OCD

OHSU neurosurgeon Ahmed Raslan, M.D., and patient Amber Pearson.
Photo Credit: OHSU/Christine Torres Hicks

A patient at Oregon Health & Science University is the first in the world to benefit from a single stimulator implanted in the brain to effectively control two life-altering conditions: seizures caused by epilepsy and compulsive behavior caused by obsessive-compulsive disorder, or OCD.

Amber Pearson, 34, of Albany, said her seizures are under better control, but the relief from her psychiatric condition is profound.

“OCD is worse than having the seizures,” she said. “Epilepsy brings limitations to my life, but OCD controlled it.”

In the case study, published in the journal Neuron, co-authors from institutions across the country describe the interactive programming of the responsive neurostimulation system, or RNS, that now functions seamlessly to control the compulsions that once ruled her life.

“Before I started treatment with my RNS, I would wash my hands until they would bleed,” Pearson said. “My hands would be so dry that bending my fingers would crack the skin of my knuckles.”

Case report shows promising results using transcranial magnetic stimulation for post-stroke ataxia

Image Credit: UCLA| Health et al. Cerebellum. October 21, 2023

In a new case report, researchers at UCLA Health describe promising results using repetitive transcranial magnetic stimulation (rTMS) in the management of post-stroke cerebellar ataxia, a debilitating condition marked by impaired coordination and balance.

Cerebellar ataxia describes a group of neurological disorders that affect coordination, balance, and control of muscle movements. It results from damage or dysfunction of the cerebellum, a part of the brain responsible for coordinating voluntary movements. Ataxia can manifest as unsteady walking, difficulties with fine motor skills, and problems with speech, among other symptoms. The severity of ataxia can vary from mild to severe, and treatments often aim to manage symptoms and improve a person's quality of life as treatment options are limited.

Writing in The Cerebellum, researchers led by Evan Hy Einstein, Department of Psychiatry & Biobehavioral Sciences at the UCLA David Geffen School of Medicine, report on the case of a 58-year-old male who had experienced a cerebellar hemorrhage approximately 12 years previously. Despite intensive rehabilitation, symptoms such as slow and unsteady gait, balance issues, and urinary incontinence persisted over the years. The patient sought consultation for potential rTMS treatment. His primary complaints focused on his slow and unsteady gait, along with challenges related to balance and stability. The decision was made to employ bilateral cerebellar rTMS, representing an innovative approach to address the condition.

How Huntington’s Disease Begins Before Symptoms Appear

A microglia cell (shown in green) and corticostriatal synapses (purple) from a patient with Huntington’s disease.
Image Credit: Dan Wilton

A new study led by researchers at Boston Children’s Hospital and Harvard Medical School reveals how the process of Huntington’s disease begins well before symptoms appear — and shows that in mice, the process can be blocked to prevent cognitive problems related to Huntington’s.

If the findings hold true in humans, they raise the possibility of intervening early in the disease in people who carry the Huntington’s gene mutation.

The work, published in Nature Medicine, also could shed light on other neurodegenerative disorders.

The team found in patient tissue samples and mouse models that two players in the immune system — complement proteins and microglia — are activated very early in Huntington’s, leading to loss of synapses in the brain before cognitive and motor symptoms emerge. The researchers revealed how and where the synapses are lost.

The findings corroborate a potential treatment that’s currently in clinical trials for the disease.

The study was led by senior author Beth Stevens, HMS associate professor of neurology at Boston Children’s, and first author Dan Wilton, HMS research fellow in neurology in the Stevens lab.

UConn Health Researchers Find that Youthful Proteins Help Nerves Regrow

Three sections of optic nerve were injured by crushing (the white diamond on the far left of each nerve marks the crush point.) The lower two nerves each express genes (Rpl7 or Rpl7a) newly identified by the Trakhtenberg lab as promoting nerve axon regeneration. The axons carry the bright green dye. The insets to the right show how much more axon regrowth is occurring in the nerves that express the regeneration genes, and how no regrowth happens in the normal control (top).
Image Credit: Courtesy of Trakhtenberg Lab/UConn Health

Damaged nerves of the brain, eye, and spinal cord cannot grow back. But specific gene therapies might be able to change this, leading to treatments for paralysis and other forms of nerve damage, UConn Health researchers report in the October issue of Experimental Neurology.

Axons are the long arms of nerve cells that reach from our extremities to our spinal cord, and from our eye to our brain. Injuries that smash or sever axons—and often the large bundles of axons that we commonly call nerves—can cause paralysis, blindness, lack of sexual function, or other devastating outcomes. Most of the time, these central nervous system axons don’t repair themselves, and we have no good treatments for this.

Axons fail to regenerate for several reasons. Some of them have to do with the environment the axon grows in, but another reason is that the ability to grow is lost as the nervous system matures during and after birth. The loss of key proteins prevents regrowth once an organism matures, reports a team of researchers at UConn School of Medicine.

New non-invasive form of deep brain stimulation could provide alternative treatment for brain diseases

Photo Credit: Helix Centre

Researchers at the UK Dementia Research Institute have developed a new form of deep brain stimulation that does not require surgery and could provide an alternative treatment option for brain diseases such as Alzheimer’s.

The exciting new technology has been successfully trialed with 20 healthy volunteers for the first time by Dr Nir Grossman and Dr Ines Violante and the team at the UK Dementia Research Institute (UK DRI) at Imperial College London and the University of Surrey.

Known as temporal interference (TI), it works by safely delivering differing frequencies of electrical field through electrodes placed on the scalp and different parts of the head. The overlapping electrical fields enable a deep region of the brain known as the hippocampus to be targeted by electrical stimulation, without affecting the surrounding areas – a procedure that until now required brain surgery. 

New insights into the genetics of the common octopus: genome at the chromosome level decoded

Octopus vulgaris
Photo Credit: ©Antonio, Valerio Cirillo (BEOM SZN), 2023

Octopuses are fascinating animals – and serve as important model organisms in neuroscience, cognition research and developmental biology. To gain a deeper understanding of their biology and evolutionary history, validated data on the composition of their genome is needed, which has been lacking until now. Scientists from the University of Vienna together with an international research team have now been able to close this gap and, in a study, determined impressive figures: 2.8 billion base pairs - organized in 30 chromosomes. What sounds so simple is the result of complex, computer-assisted genome analyses and comparisons with the genomes of other cephalopod species. This groundbreaking research has just been published in the renowned journal G3: Genes / Genomes / Genetics.

Octopuses, together with squid and cuttlefish, belong to a group of coleoid cephalopods consisting of several hundreds of species that are characterized by highly diversified lifestyles, body structure and adaptations to their environment. The study of these animals looks back on a long tradition, especially since the neuronal plasticity of the octopus brain – meaning the brain's ability to change and adapt as you learn and experience new things – provides evidence for the existence of functionally analogous structures to the brains of mammals. This is making them a comparative model group for neurophysiological studies. Also, their ability to regenerate parts of their bodies as well as the rapid changes of their body patterns, which are important for camouflage and communication, make octopuses a popular research subject for studying how these innovative traits arose – and how they have changed – during evolution.

Scientists discover links between Alzheimer’s disease and gut microbiota

Photo (L-R): Dr Stefanie Grabrucker (a postdoctoral researcher) and Professor Yvonne Nolan, of APC Microbiome Ireland and the Department of Anatomy and Neuroscience.
Photo Credit: Ms Bereniece Riedewald.

Researchers have discovered the link between gut microbiota and Alzheimer’s disease.

For the first time, researchers have found that Alzheimer’s symptoms can be transferred to a healthy young organism via the gut microbiota, confirming its role in the disease.

The research was led by Professor Yvonne Nolan, APC Microbiome Ireland, a world leading SFI funded research center based at University College Cork (UCC), and the Department of Anatomy and Neuroscience, UCC, with Professor Sandrine Thuret at King’s College London and Dr Annamaria Cattaneo IRCCS Fatebenefratelli, Italy. The study supports the emergence of the gut microbiome as a key target for investigation in Alzheimer’s disease due to its particular susceptibility to lifestyle and environmental influences.

Published in Brain, the study shows that memory impairments in people with Alzheimer’s could be transferred to young animals through transplant of gut microbiota. Alzheimer’s patients had a higher abundance of inflammation-promoting bacteria in fecal samples, and these changes were directly associated with their cognitive status.

New Research Suggests Why Males and Females Respond Differently to Social Stress

Emily Wright, researcher, in a UC Davis lab.
Photo Credit: Jerry Tsai

Women are nearly twice as likely as men to be diagnosed with an anxiety disorder, but among boys and girls the likelihood is the same. New University of California, Davis, research has identified changes in the brain during puberty that may account for differences in how women and men respond to stress.

A team of psychologists has found that testosterone is the key hormone that drives gender-based differences in responses to social stress. The study encompassed six separate experiments with mice to isolate what changes in the brain drive these differences between males and females. The study was published in the Proceedings of the National Academy of Sciences, or PNAS, today.

“This research shows how the body’s hormones shape the complex interplay between the brain’s circuitry and behavioral responses to stress,” said Brian Trainor, a professor of psychology in the College of Letters and Science at UC Davis and the study’s corresponding author.

Fluctuating blood pressure: a warning sign for dementia and heart disease

Photo Credit: CDC

A new study by Australian researchers has shown that fluctuating blood pressure can increase the risk of dementia and vascular problems in older people.

Short blood pressure (BP) fluctuations within 24 hours as well as over several days or weeks are linked with impaired cognition, say University of South Australia (UniSA) researchers who led the study.

Higher systolic BP variations (the top number that measures the pressure in arteries when a heart beats) are also linked with stiffening of the arteries, associated with heart disease.

The findings have been published in the journal Cerebral Circulation – Cognition and Behavior.

Lead author Daria Gutteridge, a PhD candidate based in UniSA’s Cognitive Ageing and Impairment Neuroscience Laboratory (CAIN), says it’s well known that high blood pressure is a risk factor for dementia, but little attention is paid to fluctuating blood pressure.

“Clinical treatments focus on hypertension, while ignoring the variability of blood pressure,” Gutteridge says.