NS/ Researchers design “e-Nose” that could sniff out Parkinson’s
Neuroscience biweekly vol. 53, 16th February — 2nd March
TL;DR
- A couple of years ago, a woman named Joy Milne made headlines when scientists discovered that she could “smell” Parkinson’s disease (PD) on people with the neurodegenerative disorder. Since then, researchers have been trying to build devices that could diagnose PD through odor compounds on the skin. Now, researchers reporting in ACS Omega have developed a portable, artificially intelligent olfactory system, or “e-nose,” that could someday diagnose the disease in a doctor’s office.
- Scientists have developed a new technique that uses microscopic magnetic particles to remotely activate brain cells; researchers say the discovery in rats could potentially lead to the development of a new class of non-invasive therapies for neurological disorders.
- Researchers are simultaneously recording populations of neurons across brain areas in the visual system and utilizing novel statistical methods to observe neural activity patterns being conveyed.
- Neurons are constantly performing complex calculations to process sensory information and infer the state of the environment. For example, to localize a sound or to recognize the direction of visual motion, individual neurons are thought to multiply two signals. However, how such a computation is carried out has been a mystery for decades. Researchers have now discovered in fruit flies the biophysical basis that enables a specific type of neuron to multiply two incoming signals. This provides fundamental insights into the algebra of neurons — the computations that may underlie countless processes in the brain.
- It has long been known that oscillatory neural activity is a key factor for attentional selection in the mammalian brain. Scientists have now investigated how this works. They found that coupling lower frequencies of oscillations with higher ones allows fine-tuning the brain and is thus the basis for higher cognitive functions, such as selective attention.
- A new study has found that hippocampal neurons in rats accurately map the position of a moving object even while the rat is stationary. The results challenge the idea that the hippocampus, a region of the brain involved in learning and memory, only encodes a map of space based on movement.
- Researchers have developed a new method for controlled interrogation and recording neuronal activity. The system combines technology from multichannel optogenetics with laminar recordings in the brain. The research team proposes an alternative design for silicon probes and develops fibers with a Lambertian emission.
- A joint research team at the Medical University of South Carolina (MUSC) and the University of Florida describes the first non-invasive and near real-time visualization of the human brain’s waste-clearance system in Nature Communications. The brain is densely organized, and visualizing the structures dedicated to waste removal, also known as lymphatic structures, had been a limitation in the field.
- UNLV-led research team identifies key brain protein to target for new customized drug therapies treating adverse symptoms of developmental disorder subtypes.
- Researchers discovered that a brief 15-minute walk in a hot outdoor environment impairs cognitive function. Moreover, this effect was most pronounced in sleep-deprived men and could negatively impact the productivity and learning of workers and students in urban cities in the summer months.
- And more!
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Latest news and researches
Artificial Intelligent Olfactory System for the Diagnosis of Parkinson’s Disease
by Fu W, Xu L, Yu Q, et al. in ACS Omega.
A couple of years ago, a woman named Joy Milne made headlines when scientists discovered that she could “smell” Parkinson’s disease (PD) on people with the neurodegenerative disorder. Since then, researchers have been trying to build devices that could diagnose PD through odor compounds on the skin. Now, researchers reporting in ACS Omega have developed a portable, artificially intelligent olfactory system, or “e-nose,” that could someday diagnose the disease in a doctor’s office.
PD causes motor symptoms, such as tremors, rigidity and trouble walking, as well as non-motor symptoms, including depression and dementia. Although there’s no cure, early diagnosis and treatment can improve one’s quality of life, relieve symptoms and prolong survival. However, the disease usually isn’t identified until patients develop motor symptoms, and by that time, they’ve already experienced irreversible neuron loss.
Recently, scientists discovered that people with PD secrete increased sebum (an oily, waxy substance produced by the skin’s sebaceous glands), along with increased production of yeast, enzymes and hormones, which combine to produce certain odors. Although human “super smellers” like Milne are very rare, researchers have used gas chromatography (GC)-mass spectrometry to analyze odor compounds in the sebum of people with PD. But the instruments are bulky, slow and expensive. Jun Liu, Xing Chen and colleagues wanted to develop a fast, easy to use, portable and inexpensive GC system to diagnose PD through smell, making it suitable for point-of-care testing.
The researchers developed an e-nose, combining GC with a surface acoustic wave sensor — which measures gaseous compounds through their interaction with a sound wave — and machine learning algorithms. The team collected sebum samples from 31 PD patients and 32 healthy controls by swabbing their upper backs with gauze. They analyzed volatile organic compounds emanating from the gauze with the e-nose, finding three odor compounds (octanal, hexyl acetate and perillic aldehyde) that were significantly different between the two groups, which they used to build a model for PD diagnosis.
Next, the researchers analyzed sebum from an additional 12 PD patients and 12 healthy controls, finding that the model had an accuracy of 70.8% in predicting PD. The model was 91.7% sensitive in identifying true PD patients, but its specificity was only 50%, indicating a high rate of false positives. When machine learning algorithms were used to analyze the entire odor profile, the accuracy of diagnosis improved to 79.2%. Before the e-nose is ready for the clinic, the team needs to test it on many more people to improve the accuracy of the models, and they also need to consider factors such as race, the researchers say.
Dynamic coupling of oscillatory neural activity and its roles in visual attention
by Moein Esghaei, Stefan Treue, Trichur R. Vidyasagar in Trends in Neurosciences
Focusing on what’s important — is one of the main tasks of our brain. After all, countless amounts of information are constantly flooding our senses. But how do we manage to separate the important from the unimportant? It has long been known that oscillatory neural activity is a key factor for this attentional selection in the mammalian brain. Scientists from the German Primate Center in Göttingen and the University of Melbourne have now investigated how this works. They found that coupling lower frequencies of oscillations with higher ones allows fine-tuning the brain and is thus the basis for higher cognitive functions, such as selective attention.
Contrary to our intuition, the precision with which we perceive the real world is not stable in time, rather it rhythmically fluctuates between high precision and low precision states several times per second. These fluctuations follow rhythmic electrical activities in the brain. Electrical rhythms of the brain range across different frequencies, from 1 to 250 hertz. Using these different frequencies the brain regulates how relevant information is transmitted between different brain regions. A group of neuroscientists from the German Primate Centre, Goettingen, Germany and the University of Melbourne, Australia has critically reviewed the evidence on this subject and shows how these frequencies may determine fundamental perceptual processes in the brain.
One basic phenomenon observed throughout brain areas is that slower rhythms (approx. 4 to 8 hertz) modulate the strength of a faster rhythm (approx. 40 to 80 hertz). This is known as cross-frequency coupling. The pair of frequencies coupled to each other varies, based upon the cortical area and its function for behavior. In some instances, attention may cause nerve cells to become de-synchronized, allowing them to carry different information, like when one string instrument plays a different melody from the rest of the orchestra. In others, attention may lead to the activation of large numbers of neurons to maximize their impact.
“These two different functions may be organized in the brain through cross frequency coupling,” says Moein Esghaei, one of the authors.
The simultaneous existence of different frequency bands in the brain also helps tagging different modalities of information arriving at the same brain region. For example, the colour and direction of a hang glider flying in the sky.
“Our brain routes information about color and motion through different frequencies to higher order brain areas, just like telecommunication systems transmitting different types of information to the same receiver,” says Moein Esghaei.
“The rhythmic activity of neuronal networks plays a critical role for visual perception in humans and other primates,” summarizes Stefan Treue, head of the Cognitive Neuroscience Laboratory at the German Primate Center as a co-author. “Understanding how exactly these activity patterns interact and are controlled, not only helps us to better understand the neural basis of perception, but also may help to elucidate some of the perceptual deficits in neurological conditions, such as dyslexia, ADHD, and schizophrenia.”
Remote and Selective Control of Astrocytes by Magnetomechanical Stimulation
by Yichao Yu, Christopher Payne, Nephtali Marina, Alla Korsak, Paul Southern, Ana García‐Prieto, Isabel N. Christie, Rebecca R. Baker, Elizabeth M. C. Fisher, Jack A. Wells, Tammy L. Kalber, Quentin A. Pankhurst, Alexander V. Gourine, Mark F. Lythgoe in Advanced Science
Scientists at UCL have developed a new technique that uses microscopic magnetic particles to remotely activate brain cells; researchers say the discovery in rats could potentially lead to the development of a new class of non-invasive therapies for neurological disorders.
Published in Advanced Science, the pioneering technique called “magnetomechanical stimulation” or , allows touch sensitive brain glial cells called astrocytes to be stimulated with a magnetic device outside the body.
Microscopic magnetic particles, or micromagnets, are attached to astrocytes, and used as miniature mechanical switches that can turn “on” the cells when a strong magnet is placed near the head.
Co-author, Professor Alexander Gourine (UCL Centre for Cardiovascular and Metabolic Neuroscience) said:
“Astrocytes are star-shaped cells found throughout the brain. They are strategically positioned between the brain blood vessels and nerve cells. These cells provide neurons with essential metabolic and structural support, modulate neuronal circuit activity and may also function as versatile surveyors of brain milieu, tuned to sense conditions of potential metabolic insufficiency.
“The ability to control brain astrocytes using a magnetic field gives the researchers a new tool to study the function of these cells in health and disease that may be important for future development of novel and effective treatments for some common neurological disorders, such as epilepsy and stroke.”
Senior author, Professor Mark Lythgoe (UCL Centre for Advanced Biomedical Imaging) said:
“Because astrocytes are sensitive to touch, decorating them with magnetic particles means you can give the cells a tiny prod from outside the body using a magnet, and as such, control their function. This ability to remotely control astrocytes provides a new tool for understanding their function and may have the potential to treat brain disorders.”
In developing MMS, scientists at UCL set out to create a more clinically relevant brain cell control technique. This contrasts with other existing research tools, such as optogenetics and chemogenetics, which require foreign genes to be inserted into the brain cells, typically with the help of a virus. This need for genetic modification has been a major obstacle to the clinical translation of the existing methods.
Lead researcher Dr Yichao Yu (UCL Centre for Advanced Biomedical Imaging) said: “Our new technology uses magnetic particles and magnets to remotely and precisely control brain cell activity and, importantly, does this without introducing any device or foreign gene into the brain.
“In the laboratory-based study, we coated microscopic magnetic particles with an antibody that enables them to bind specifically to astrocytes. The particles were then delivered to the target brain region in the rat via injection.
“Another advantage of using micromagnets is that they light up on an MRI scan so we can track their location and target very particular parts of the brain to get precise control of brain function.”
Professor Lythgoe, who received the Royal Society of Medicine Ellison-Cliffe Award 2021 for his “contribution of fundamental science to the advancement of medicine,” added:
“We are very excited about this technology because of its clinical potential. In contrast to existing methods, MMS takes advantage of the remarkable sensitivity to touch of certain brain cells, therefore neither genetic modification nor device implantation is needed. This makes MMS a promising candidate as an alternative, less invasive therapy compared to the currently used deep brain stimulation techniques that require the insertion of electrodes into the brain.”
Feedforward and feedback interactions between visual cortical areas use different population activity patterns
by João D. Semedo, Anna I. Jasper, Amin Zandvakili, Aravind Krishna, Amir Aschner, Christian K. Machens, Adam Kohn, Byron M. Yu in Nature Communications
Exploring how brain areas communicate with each other is the focus of a long-standing research collaboration between Carnegie Mellon University, Albert Einstein College of Medicine, and Champalimaud Research. The cross-continental team is simultaneously recording populations of neurons across multiple brain areas in the visual system and utilizing novel statistical methods to observe neural activity patterns being conveyed between the areas. Their latest findings reveal that feedforward and feedback signaling involve different neural activity patterns, lending fresh understanding into how the brain processes visual information.
A myriad of brain functions, such as seeing, hearing, and making decisions, require multiple brain areas to communicate with one another. Researchers have previously studied pairs of neurons or some aggregate metric of neuronal activity across areas to assess how information is taken in, processed, and then acted upon in everyday life. Few groups have studied, in such detail, populations of neurons together to see what type of activity patterns are being communicated across brain areas.
“The idea of this study was to investigate how information flows across two areas in the visual cortex, V1 and V2,” says João D. Semedo, first author of the work published in Nature Communications and former electrical and computer engineering Ph.D. student. “We had strong reasons to believe that the areas communicated with one another, based on anatomy, but tracking the flow of signals between areas has proven to be really difficult.”
Semedo continues,
“Using pioneering technology from Dr. Kohn’s lab, we have been able to record multiple brain areas at the same time, and within each of those brain areas, record many neurons. It is the activity of a group of neurons together that tells us what is specifically going on. Then, we applied statistical methods in a creative way to pull out signals that haven’t been extracted before.”
In their analysis, the group identified directed interactions between brain areas and confirmed that patterns of activity in feedforward interactions (from V1 to V2), differed from patterns of activity in feedback interactions (from V2 to V1). Weekly meetings and a tight-knit, teamwork-driven approach has enabled the collaborators to stay connected on all aspects of the work and contributed to their success.
“Understanding what is communicated from one brain area to another is tough to disentangle, because signals are flowing in all directions, all the time,” explains Adam Kohn, professor of neuroscience at the Albert Einstein College of Medicine. “The thing that is most exciting to me about this work is the perspectives it opens for the future. If we can pinpoint the activity patterns that are involved in different signaling directions, it will be a big step forward in understanding how the brain works.”
More broadly, these methods could be applied to investigate the flow of communication in other areas of the brain, outside of the visual system.
“Studies like these increase our basic scientific understanding of how the brain works,” says Byron Yu, professor of biomedical engineering and electrical and computer engineering. “Many brain disorders involve a breakdown of communication between brain areas. This pioneering work could lead to novel treatments for such disorders, and even help us develop new methods to aid brain development and ways to learn.”
A biophysical account of multiplication by a single neuron
by Lukas N. Groschner, Jonatan G. Malis, Birte Zuidinga, Alexander Borst in Nature
Neurons are constantly performing complex calculations to process sensory information and infer the state of the environment. For example, to localize a sound or to recognize the direction of visual motion, individual neurons are thought to multiply two signals. However, how such a computation is carried out has been a mystery for decades. Researchers at the Max Planck Institute for Biological Intelligence, in foundation (i.f.), have now discovered in fruit flies the biophysical basis that enables a specific type of neuron to multiply two incoming signals. This provides fundamental insights into the algebra of neurons — the computations that may underlie countless processes in the brain.
We easily recognize objects and the direction in which they move. The brain calculates this information based on local changes in light intensity detected by our retina. The calculations occur at the level of individual neurons. But what does it mean when neurons calculate? In a network of communicating nerve cells, each cell must calculate its outgoing signal based on a multitude of incoming signals. Certain types of signals will increase and others will reduce the outgoing signal — processes that neuroscientists refer to as ‘excitation’ and ‘inhibition’.
Theoretical models assume that seeing motion requires the multiplication of two signals, but how such arithmetic operations are performed at the level of single neurons was previously unknown. Researchers from Alexander Borst’s department at the Max Planck Institute for Biological Intelligence, i.f., have now solved this puzzle in a specific type of neuron.
The scientists focused on so-called T4 cells in the visual system of the fruit fly. These neurons only respond to visual motion in one specific direction. The lead authors Jonatan Malis and Lukas Groschner succeeded for the first time in measuring both the incoming and the outgoing signals of T4 cells. To do so, the neurobiologists placed the animal in a miniature cinema and used minuscule electrodes to record the neurons’ electrical activities. Since T4 cells are among the smallest of all neurons, the successful measurements were a methodological milestone.
Together with computer simulations, the data revealed that the activity of a T4 cell is constantly inhibited. However, if a visual stimulus moves in a certain direction, the inhibition is briefly lifted. Within this short time window, an incoming excitatory signal is amplified: Mathematically, constant inhibition is equivalent to a division; removing the inhibition results in a multiplication.
“We have discovered a simple basis for a complex calculation in a single neuron,” explains Lukas Groschner. “The inverse operation of a division is a multiplication. Neurons seem to be able to exploit this relationship,” adds Jonatan Malis.
The T4 cell’s ability to multiply is linked to a certain receptor molecule on its surface.
“Animals lacking this receptor misperceive visual motion and fail to maintain a stable course in behavioral experiments,” explains co-author Birte Zuidinga, who analyzed the walking trajectories of fruit flies in a virtual reality setup.
This illustrates the importance of this type of computation for the animals’ behavior.
“So far, our understanding of the basic algebra of neurons was rather incomplete,” says Alexander Borst. “However, the comparatively simple brain of the fruit fly has allowed us to gain insight into this seemingly intractable puzzle.”
The researchers assume that similar neuronal computations underlie, for example, our abilities to localize sounds, to focus our attention, or to orient ourselves in space.
Moving bar of light evokes vectorial spatial selectivity in the immobile rat hippocampus
by Chinmay S. Purandare, Shonali Dhingra, Rodrigo Rios, Cliff Vuong, Thuc To, Ayaka Hachisuka, Krishna Choudhary, Mayank R. Mehta in Nature
Understanding how the brain creates a map of the space around us has implications for research into learning and memory disorders ranging from autism to Alzheimer’s disease, where subjects often have an incorrect perception of space-time and events. Previously, it was thought that only neurons in the visual cortex were able to map the position of moving objects, and that the hippocampus, the memory-making part of the brain, required spatial exploration or a cognitive task in order to contribute.
A new UCLA study has found that hippocampal neurons in rats accurately map the position of a moving object even while the rat is stationary. The results challenge the idea that the hippocampus, a region of the brain involved in learning and memory, only encodes a map of space based on movement.
Panel a) shows the rat seated in the midst of augmented reality setup with a green bar of light moving around him. Panel b) shows the top down view of the maze. Panel c) shows the activity of four different neurons as a function of the position of the bar. Neurons encode the angular position of the bar of light even when the rat is not moving, thus challenging the prevailing hypothesis that the hippocampus requires exploration to create an abstract map of space. (Graphic courtesy of Dr. Mayank Mehta).
These new findings resolve long-standing puzzles about hippocampal function and open up many new avenues to develop early diagnosis and treatment for memory disorders, says Mayank R. Mehta, PhD, head of the W. M. Keck Center for Neurophysics at UCLA and a professor in the departments of physics, neurology, and electrical and computer engineering at UCLA.
“For example,” he said, “it allows scientists to study cognitive deficits such as a subject’s memory of events around them — the most common deficit in Alzheimer’s.”
The study, published in Nature, was conducted by scientists from the W. M. Keck Center for Neurophysics at UCLA, including lead authors Chinmay Purandare, PhD, and Shonali Dhingra, PhD.
Using a modified virtual reality maze for rats developed to probe the hippocampus’s memory function, researchers created a single bar of light on the VR screen that moved all around the rat — “as if a person was walking around you while you’re seated,” Dr. Mehta explained. Previous studies had found that such simple stimuli did not trigger the hippocampus. UCLA researchers, hypothesizing that the reason for that was the size of the stimuli, made the size of the bar large from the rat’s perspective.
By measuring neural signals, they found a majority of neurons in the rat’s hippocampus responded to the bar of light, logging its exact position, the direction in which it was moving, and even its distance and angular degree from the rat. The neurons also encoded identifying characteristics of the bar of light, such as its color and texture.
The results overturn the idea that the hippocampus requires movement in space to create a spatial map.
The neural response “is quite similar to activity patterns in the visual cortices,” Dr. Mehta said. “That makes sense since the visual cortex is a major source of input to the hippocampus.”
The team plans to continue using the VR system for experiments into understanding the neural activity of patients, including those with memory deficits such as Alzheimer’s disease.
Multichannel optogenetics combined with laminar recordings for ultra-controlled neuronal interrogation
by David Eriksson, Artur Schneider, Anupriya Thirumalai, Mansour Alyahyay, Brice de la Crompe, Kirti Sharma, Patrick Ruther, Ilka Diester in Nature Communications
In the field of optogenetics, scientists investigate the activity of neurons in the brain using light. A team led by Prof. Dr. Ilka Diester and Dr. David Eriksson from the Optophysiology Laboratory at the University of Freiburg has developed a new method to simultaneously conduct laminar recordings, multifiber stimulations, 3D optogenetic stimulation, connectivity inference, and behavioral quantification on brains. Their results are presented in Nature Communications. “Our work paves the way for large-scale photo-recording and controlled interrogation of fast neural communication in any combination of brain areas,” Diester explains. “This can help us unravel the rapid and multilayered dialogues between neurons that maintain brain function.”
The research group, in collaboration with Dr. Patrick Ruther of the Department of Microsystems Engineering (IMTEK) at the University of Freiburg, is developing a new method for the controlled interrogation and recording of neuronal activity in the brain. To do this, the team is taking advantage of thin, cell-sized optical fibers for minimally invasive optogenetic implantation.
“We combine side-emitting fibers with silicon probes to achieve high-quality recordings and ultrafast, multichannel optogenetic control.”
They call the system Fused Fiber Light Emission and eXtracellular Recording, or FFLEXR. In addition to optical fibers that can be attached to any silicon probe, the team uses linear depth-resolved stimulation, a lightweight fiber matrix connector, a flexible multifiber ribbon cable, an optical commutator for efficient multichannel stimulation, a general-purpose patch cable, and an algorithm to manage the photovoltaic response.
“Our alternative approach maintains the flexibility to apply any desired wavelength via an external interchangeable light source and enable optogenetic stimulation at different depths of brain tissue,” Diester says.
Ilka Diester heads a research group at the Institute of Biology III and research center IMBIT/BrainLinks-BrainTools at the University of Freiburg that uses optophysiology, i.e. novel optical tools, to investigate the functioning of neuronal circuits. The scientists are investigating the neuronal basis of motor and cognitive control as well as interactions between the prefrontal and motor cortex, both of which are part of the cerebral cortex.
Non-invasive MR imaging of human brain lymphatic networks with connections to cervical lymph nodes
by Albayram MS, Smith G, Tufan F, et al. in Nature Communications
A joint research team at the Medical University of South Carolina (MUSC) and the University of Florida describes the first non-invasive and near real-time visualization of the human brain’s waste-clearance system in Nature Communications. The brain is densely organized, and visualizing the structures dedicated to waste removal, also known as lymphatic structures, had been a limitation in the field.
“This is the first report to show the complete human brain lymphatic system architecture in living humans,” said Onder Albayram, Ph.D., an assistant professor in the Department of Pathology and Laboratory Medicine and Department of Neuroscience at MUSC, who led the research team and is senior author of the article.
Albayram was intrigued by the possibility of lymphatic structures in the brain. “The lymphatic clearance system is all over the body for different organs,” he said. “I asked myself simply, ‘Why not the brain?’”
Improved visualization of the brain’s waste-clearance system could enhance our understanding of how the healthy brain functions. It could also provide insight into what goes wrong in neurogenerative diseases such as Alzheimer’s and how the brain recovers from traumatic brain injuries (TBIs).
Pound for pound, the brain is the most metabolically demanding mass in the body — weighing around 3 pounds but requiring 20% of total oxygen consumption. That metabolic demand comes with the need to dispose of waste regularly.
As blood carrying oxygen permeates tissues to deliver vital nutrients, it collects pathogens, damaged cells and waste. This fluid then drains into lymphatic vessels to be filtered through lymph nodes, which dispose of any unwanted waste products.
“It had long been believed that the brain lacked lymphatic vessels,” said Sait Albayram, M.D., a professor in the Department of Neuroradiology at the University of Florida, who is the lead author of the article.
“That thinking began to change about a decade ago, as the first reports from experiments in rodents hinted at lymphatic vessels surrounding the brain, side by side with blood vessels. But evidence of lymphatic vessels in human brains remained scarce before this study.”
Onder Albayram likens the brain in the skull to an apple suspended inside of a jar. Coating the inside of the “jar,” or skull, is a layer of delicate membranes known as the meninges. A liquid known as cerebrospinal fluid (CSF) surrounds the brain. The conventional thinking was that waste-laden fluid from the brain flowed out into the CSF along blood vessels, was transported out of the skull and then drained into veins. Research over the past decade has hinted instead that the process is more complex and suggested the existence of dedicated waste-removing lymphatic vessels in the brain.
However, witnessing these vessels in action in a living human brain has posed technical limitations. Chief among them is the required use of the toxic rare-earth metal, Gadolinium, a toxic rare-earth metal used as a contrast agent during MRI, a technique used to visualize and differentiate structures in the brain.
In this study, investigators were able to overcome this limitation and use MRI to visualize lymphatic vessels in the meninges without the need for contrast agent. Instead, the team used differences in the brain’s own protein content to create a gradient in contrast. Structures with low protein content appear dark and those with high protein content appear light, with high enough resolution to see intricate details.
“The discovery of the meningeal lymphatic networks in mammals in the last decade opened a new chapter in our understanding of cellular waste management in the brain,” said Adviye Ergul, M.D., Ph.D., a professor in the Department of Pathology and Laboratory Medicine at MUSC, who was not an author of the study.
“This novel study takes it one step further by eliminating the need to inject contrast agents to visualize the lymphatic vessels,” she said. “This is a major accomplishment that will invigorate the field to go deeper into the brain and expand our knowledge of the brain lymphatic system.”
This simple yet innovative approach enabled investigators to capture clear images of lymphatic vessels, with their high protein content — about 50-fold greater than that of CSF — as they connected areas within the brain to lymph nodes in the neck.
The research team then went on to compare how aged brains differ from younger ones, finding a reduction in waste clearance in older brains.
Using this non-invasive MRI technique, researchers and physicians can now actually see what the lymphatic vessels of a healthy brain look like, said Onder Albayram, and study how they change as we age. They can also determine their role in the progression of neurodegenerative diseases, such as Alzheimer’s and related dementia. The technique could also be used to study ways to increase the brain’s lymphatic output as we age and perhaps offer insight into recovery after TBI.
“Imagine again the brain in the jar, surrounded by delicate lymphatic vessels,” said Onder Albayram. “What happens during a TBI? Are the lymphatic vessels damaged, and how do they recover? This technique will enable us to begin to answer these questions.”
Human ARHGEF9 intellectual disability syndrome is phenocopied by a mutation that disrupts collybistin binding to the GABAA receptor α2 subunit
by Dustin J. Hines, April Contreras, Betsua Garcia, Jeffrey S. Barker, Austin J. Boren, Christelle Moufawad El Achkar, Stephen J. Moss, Rochelle M. Hines in Molecular Psychiatry
Science is one step closer to developing targeted drug therapies that may reduce seizures, sleep disorders, and related symptoms common in people with intellectual disabilities.
Research led by a team of UNLV neuroscientists has shown the potential to zero in on the root-level cause of a host of adverse symptoms associated with unique subtypes of neurodevelopmental disorders, work that could one day improve the lives of millions worldwide.
The study builds on previous research by UNLV neuroscientist Rochelle Hines and collaborators, which discovered that two key proteins — collybistin and the GABAA receptor subunit — control the firing of brain cells and contribute to epileptic seizures, learning and memory deficiencies, sleep disturbances, and other symptoms frequently associated with various forms of intellectual disability including Down syndrome, autism, and ADHD.
The team’s newest findings unveiled that mutations in ARHGEF9 — the gene that codes for collybistin — lead to intellectual disability through impaired subunit function. The team further showed that is a central hub for many of the adverse neurological symptoms characteristic of multiple intellectual disability subtypes.
“Seizures and sleep deficits are two of the most common and most disruptive symptoms in children with neurodevelopmental disorders, and sleep deficits in particular are not well treated and can impact the entire family,” said Hines, who partnered with UNLV faculty and undergraduate and graduate student researchers, as well as scientists from Tufts University and Boston Children’s Hospital. “This research gives new hope to patients that we can now develop drug therapies and provide more precise interventions.”
In addition to patients with neurodevelopmental disorders, researchers said their study has the potential to improve the quality of life more broadly for people who grapple with sleep dysfunction, epilepsy, anxiety, hyperactivity, and other neurological abnormalities.
Takeaways
- Intellectual disability is a common neurodevelopmental disorder that can arise from genetic mutations. People with these disorders — Down syndrome and autism are the most prevalent — frequently report related symptoms such as epileptic seizures, learning and memory difficulties, and disrupted sleep-wake cycles.
- By manipulating interaction between two key brain proteins, scientists discovered that one of them — called the subunit — plays a more critical role in intellectual disability and related symptoms than researchers previously thought.
- Knowing which functional interaction is responsible for triggering adverse effects caused by ARHGEF9 gene mutations will help researchers develop precise drug interventions — providing enhanced care to patients.
- Further research is underway, with the hope that the work may one day advance to clinical trials.
Effect of walking in heat-stressful outdoor environments in an urban setting on cognitive performance indoors
by Yuki Asano, Yusuke Nakamura, Asuka Suzuki-Parker, Shohei Aiba, Hiroyuki Kusaka in Building and Environment
Studies have shown that being in a hot environment reduces cognitive performance, whereas a brief walk enhances cognition. But what happens when you go for a brief walk on a hot summer’s day, as so many students and office workers do during lunch or an afternoon break? Turns out, you might be better off avoiding the heat.
In a study published this month in Building and Environment, researchers from the University of Tsukuba discovered that just 15 minutes of walking outside on a hot day impaired cognitive performance, and this was most striking in men who don’t get enough sleep.
Those who work or study in urban heat islands, such as large cities in Japan, generally have the convenience of air-conditioning indoors over the summer months, which largely counters the negative impact of heat on learning and productivity. However, brief exposure to hot environments during commuting or breaks is inevitable, and whether such exposure affects cognition has not been known.
“Previous experiments have used specialized climate chambers to test these effects. However, outdoor thermal environment differs significantly from indoor thermal environments in terms of radiation and wind,” says senior author Professor Hiroyuki Kusaka. “Radiation and wind have significant effects on thermal perception. Therefore, in order to assess the effects of outdoor heat stress on cognitive performance, experiments should be conducted in real outdoor environments.”
Researchers simulated a real-world scenario during the Japanese summer in which workers or students leave an air-conditioned indoor environment to walk or have a break in a hot outdoor urban environment. Ninety-six students completed a simple arithmetic test in an air-conditioned room before either staying indoors, walking outside, or resting outside for 15 minutes. They then returned indoors to complete a second arithmetic test, and any changes in performance were measured. Walking in a hot outdoor environment impaired cognitive performance; however, it was not simply the exposure to the hot environment that impaired cognition. Rather, it was the combination of walking and being outside in the summer heat that had impacted cognitive performance. Furthermore, this effect was more pronounced in people, specifically men, who were sleep deprived, having slept less than 5 hours.
“Japanese office workers and students, especially men, need to be aware of this situation as they work and study,” says Kusaka.
The team hopes that their findings will help guide ways to improve productivity and learning in workers and students in Japan, and perhaps even further afield as the impact of climate change moves to the forefront.
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