NS/ Spinal cord stimulation instantly improves arm mobility after a stroke
Neuroscience biweekly vol. 79, 15th February — 1st March
TL;DR
- A neurotechnology that stimulates the spinal cord instantly improves arm and hand mobility, enabling people affected by moderate to severe stroke to conduct their normal daily activities more easily, report researchers from the University of Pittsburgh and Carnegie Mellon University in Nature Medicine.
- The most common cause of hearing loss is progressive because hair cells — the primary cells to detect sound waves — cannot regenerate if damaged or lost. Researchers are now getting closer to identifying the mechanisms that may promote this type of regeneration in mammals.
- Researchers used computational modeling to uncover mutations in the human genome that likely influenced the evolution of human cognition. This groundbreaking research in human genomics could lead to a better understanding of human health and the discovery of novel treatments for complex brain disorders. The study is to be published in Science Advances.
- The study focuses on neuronal growth and migration: As nerve cells form, they wire the brain to enable communication with other nerve cells. One of these wires, the axon, becomes long; these wires are a basis for neuronal networks. At the same time, nerve cells migrate to a specific place in the brain, the cortex. Remarkably, these dynamic processes are separately controlled: The axon continues to grow to connect with its target cells even after the nerve cell has already found its final position. “We found that the centrosome — an organelle that drives cell division — regulates the nerve cell migration; for the formation and growth of the axon, however, it does not play a role,” Dr. Stanislav Vinopal and Dr. Sebastian Dupraz of the German Center for Neurodegenerative Diseases (DZNE) say. They are the first authors of the study, which now appears in the journal Neuron.
- A team from Nagoya University in Japan used the drug fasudil to reverse two common symptoms associated with schizophrenia: reduced density of pyramidal neurons and cognitive dysfunction associated with methamphetamine treatment.? Their findings, which were published in Pharmacological Research, suggest new therapeutic approaches for treating schizophrenia patients.
- Up to now, the use of models to research the barrier that separates the circulatory from the nervous system has proven to be either limited or extremely complicated. Researchers have now developed a more realistic model that can also be used to better explore new treatments for brain tumors.
- Neuroimaging techniques, like functional magnetic resonance imaging (fMRI), are not able to directly measure neuronal activity. To address this knowledge gap, a team has created a novel experimental platform that is able to optically record local neuronal activity during brain-wide fMRI in rodents.
- Scientists at the University of Antwerp and the University of Liège have found how the human brain changes and adapts to weightlessness, after being in space for 6 months. Some of the changes turned out to be lasting — even after 8 months back on Earth. Raphaël Liégeois, soon to be the third Belgian in space, acknowledges the importance of the research, “to prepare the new generation of astronauts for longer missions.”
- The findings, published in the peer-reviewed journal eNeuro, provide insight into the neural mechanisms of motor skill learning that can help lead to more effective brain-stimulation therapies for patients experiencing motor disability after a stroke.
- Children as young as 4 years old show evidence of a network in the brain found in adults that tackles difficult cognitive problems, a new study found.
- And more!
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Epidural stimulation of the cervical spinal cord for post-stroke upper-limb paresis
by Marc P. Powell, Nikhil Verma, Erynn Sorensen, Erick Carranza, Amy Boos, Daryl P. Fields, Souvik Roy, Scott Ensel, Beatrice Barra, Jeffrey Balzer, Jeff Goldsmith, Robert M. Friedlander, George F. Wittenberg, Lee E. Fisher, John W. Krakauer, Peter C. Gerszten, Elvira Pirondini, Douglas J. Weber, Marco Capogrosso in Nature Medicine
A neurotechnology that stimulates the spinal cord instantly improves arm and hand mobility, enabling people affected by moderate to severe stroke to conduct their normal daily activities more easily, report researchers from the University of Pittsburgh and Carnegie Mellon University in Nature Medicine.
A pair of thin metal electrodes resembling strands of spaghetti implanted along the neck engages intact neural circuits, allowing stroke patients to fully open and close their fists, lift their arm above their head, or use a fork and knife to cut a piece of steak for the first time in years.
“We discovered that electrical stimulation of specific spinal cord regions enables patients to move their arm in ways that they are not able to do without the stimulation. Perhaps even more interesting, we found that after a few weeks of use, some of these improvements endure when the stimulation is switched off, indicating exciting avenues for the future of stroke therapies,” said corresponding and co-senior author Marco Capogrosso, Ph.D., assistant professor of neurological surgery at Pitt. “Thanks to years of preclinical research building up to this point, we have developed a practical, easy-to-use stimulation protocol adapting existing FDA-approved clinical technologies that could be easily translated to the hospital and quickly moved from the lab to the clinic.”
When it comes to strokes, doctors predict a grim future: Globally, every fourth adult over the age of 25 will suffer a stroke in their lifetime, and 75% of those people will have lasting deficits in motor control of their arm and hand, severely limiting their physical autonomy.
Currently, no treatments are effective for treating paralysis in the so-called chronic stage of stroke, which begins approximately six months after the stroke incident. The new technology, researchers say, has the potential to offer hope for people living with impairments that would otherwise be considered permanent.
“Creating effective neurorehabilitation solutions for people affected by movement impairment after stroke is becoming ever more urgent,” said senior co-author Elvira Pirondini, Ph.D., assistant professor of physical medicine and rehabilitation at Pitt. “Even mild deficits resulting from a stroke can isolate people from social and professional lives and become very debilitating, with motor impairments in the arm and hand being especially taxing and impeding simple daily activities, such as writing, eating and getting dressed.”
Spinal cord stimulation technology uses a set of electrodes placed on the surface of the spinal cord to deliver pulses of electricity that activate nerve cells inside the spinal cord. This technology is already being used to treat high-grade, persistent pain. Additionally, multiple research groups around the world have shown that spinal cord stimulation can be used to restore movement to the legs after spinal cord injury.
But the unique dexterity of the human hand, combined with the wide range of motion of the arm at the shoulder and the complexity of the neural signals controlling the arm and hand, add a significantly higher set of challenges.
Following years of extensive preclinical studies involving computer modeling and animal testing in macaque monkeys with partial arm paralysis, researchers were cleared to test this optimized therapy in humans.
“The sensory nerves from the arm and hand send signals to motor neurons in the spinal cord that control the muscles of the limb,” said co-senior author Douglas Weber, Ph.D., professor of mechanical engineering at the Neuroscience Institute at Carnegie Mellon University. “By stimulating these sensory nerves, we can amplify the activity of muscles that have been weakened by stroke. Importantly, the patient retains full control of their movements: The stimulation is assistive and strengthens muscle activation only when patients are trying to move.”
In a series of tests adapted to individual patients, stimulation enabled participants to perform tasks of different complexity, from moving a hollow metal cylinder to grasping common household objects, such as a can of soup and opening a lock. Clinical assessments showed that stimulation targeting cervical nerve roots immediately improves strength, range of movement and function of the arm and hand.
Unexpectedly, the effects of stimulation seem to be longer-lasting than scientists originally thought and persisted even after the device was removed, suggesting it could be used both as an assistive and a restorative method for upper limb recovery. Indeed, the immediate effects of the stimulation enable the administration of intense physical training that, in turn, could lead to even stronger long-term improvements in the absence of the stimulation.
Moving forward, researchers continue to enroll additional trial participants to understand which stroke patients can benefit most from this therapy and how to optimize stimulation protocols for different severity levels.
Additionally, Pitt and CMU-founded startup Reach Neuro is working to translate the therapy into clinical use.
Single cell RNA sequencing analysis of mouse cochlear supporting cell transcriptomes with activated ERBB2 receptor indicates a cell-specific response that promotes CD44 activation
by Dorota Piekna-Przybylska, Daxiang Na, Jingyuan Zhang, Cameron Baker, John M. Ashton, Patricia M. White in Frontiers in Cellular Neuroscience
Taking a bite of an apple is considered a healthy choice. But have you ever thought about putting in earplugs before your favorite band takes the stage?
Just like your future body will thank you for the apple, your future ears (specifically your cochlear hair cells) will thank you for protecting them. The most common cause of hearing loss is progressive because these hair cells — the primary cells to detect sound waves — cannot regenerate if damaged or lost. People who have repeated exposure to loud noises, like military personnel, construction workers, and musicians, are most at risk for this type of hearing loss. But, it can happen to anyone over time (even concert goers).
On the other hand, birds and fish can regenerate these hair cells, and now researchers at the Del Monte Institute for Neuroscience are getting closer to identifying the mechanisms that may promote this type of regeneration in mammals, as explained in research recently published in Frontiers in Cellular Neuroscience.
“We know from our previous work that expression of an active growth gene, called ERBB2, was able to activate the growth of new hair cells (in mammals), but we didn’t fully understand why,” said Patricia White, PhD, professor of Neuroscience and Otolaryngology at the University of Rochester Medical Center.
The 2018 study led by Jingyuan Zhang, PhD, a postdoctoral fellow in the White lab at the time, found that activating the growth gene ERBB2 pathway triggered a cascading series of cellular events by which cochlear support cells began to multiply and activate other neighboring stem cells to become new sensory hair cells.
“This new study tells us how that activation is happening — a significant advance toward the ultimate goal of generating new cochlear hair cells in mammals,” said White.
Using single-cell RNA sequencing in mice, researchers compared cells with an overactive growth gene (ERBB2 signaling) with similar cells that lacked such signaling. They found the growth gene — ERBB2 — promoted stem cell-like development by initiating the expression of multiple proteins — including SPP1, a protein that signals through the CD44 receptor. The CD44 receptor is known to be present in cochlear-supporting cells. This increase in cellular response promoted mitosis in the supporting cells, a key event for regeneration.
“When we checked this process in adult mice, we were able to show that ERBB2 expression drove the protein expression of SPP1 that is necessary to activate CD44 and grow new hair cells,” said Dorota Piekna-Przybylska, PhD, a staff scientist in the White Lab and first author of the study. “This discovery has made it clear that regeneration is not only restricted to the early stages of development. We believe we can use these findings to drive regeneration in adults.”
“We plan to further investigation of this phenomenon from a mechanistic perspective to determine whether it can improve auditory function after damage in mammals. That is the ultimate goal,” said White.
De novo human brain enhancers created by single-nucleotide mutations
by Shan Li, Sridhar Hannenhalli, Ivan Ovcharenko in Science Advances
Researchers from the National Institutes of Health (NIH) used computational modeling to uncover mutations in the human genome that likely influenced the evolution of human cognition. This groundbreaking research in human genomics could lead to a better understanding of human health and the discovery of novel treatments for complex brain disorders. The study is to be published in Science Advances.
Human cognition is a defining feature of human evolution, setting us apart from other primates. Despite over 100 million mutations since the human-chimp split, only a small fraction has been found to be significant. To navigate this vast landscape of genomic changes, researchers from the National Library of Medicine (NLM) and the National Cancer Institute (NCI) created an artificial intelligence (AI) model of gene regulation in the human brain. The model identified thousands of mutations likely impacting neocortical development and facilitating the acquisition of mathematical abilities through altered brain gene regulation mechanisms.
When the human genome was sequenced in 2001, researchers learned that only 2% of the sequence of our genome is used for coding genes that, in turn, translate into proteins. This is the sequence information that is being used by every single cell. The function of the other 98% of our DNA — often referred to as “noncoding DNA” — remains relatively unknown. It is believed that 95% of disease associations hide within these noncoding parts of our genome.
The research group of Ivan Ovcharenko, PhD, senior investigator in the Computational Biology Branch of NLM’s Intramural Research Program teamed up with the research group of Sridhar Hannenhalli, PhD, senior investigator in NCI’s Center for Cancer Research to create an AI model that measures the effect of noncoding genome mutations on human brain function and development. This led to the identification of a group of noncoding mutations disrupting brain regulatory pathways and potentially causing various complex brain disorders, including autism.
“There are treasure islands within the sea of noncoding DNA in the human genome that are critically important for regulating human genes,” said Dr. Ovcharenko. “Mutations in these regions are largely benign, but there is a class of mutations which detrimentally impact the function of regulatory regions in the brain and affect cellular activity there. By being able to address the impact of individual mutations, we are advancing towards understanding the mechanism of complex diseases and disorders and paving the way for the development of novel therapeutic approaches.”
According to study authors, this fundamental work in human genomics is likely to have a long-ranging impact on human health and advance the research of the complex nature of the human brain.
Centrosomal microtubule nucleation regulates radial migration of projection neurons independently of polarization in the developing brain
by Stanislav Vinopal et al. in Neuron
The study focuses on neuronal growth and migration: As nerve cells form, they wire the brain to enable communication with other nerve cells. One of these wires, the axon, becomes long; these wires are a basis for neuronal networks. At the same time, nerve cells migrate to a specific place in the brain, the cortex. Remarkably, these dynamic processes are separately controlled: The axon continues to grow to connect with its target cells even after the nerve cell has already found its final position. “We found that the centrosome — an organelle that drives cell division — regulates the nerve cell migration; for the formation and growth of the axon, however, it does not play a role,” Dr. Stanislav Vinopal and Dr. Sebastian Dupraz of the German Center for Neurodegenerative Diseases (DZNE) say. They are the first authors of the study, which now appears in the journal Neuron.
Until now, experts have debated the role of the centrosome. The process of growth and migration is enabled by a dynamic skeleton of the cell, the cytoskeleton. The cytoskeleton comprises microscopic tubules, called microtubules. They form also the backbone of the axon. The microtubules can be generated by the centrosome. With their results, the participating researchers from the group of Professor Dr. Frank Bradke have solved a central puzzle in the field of neurobiology, which science has been trying to answer for years.
The fact that the growth of the axon and the control of its migratory movement are not related is an unexpected result:
“Both actions occur simultaneously and both are dependent on microtubules. And still, they are controlled independently of each other,” says Stanislav Vinopal, who, after working for the DZNE, is now conducting research at Jan Evangelista Purkyne University in Usti nad Labem, Czech Republic.
For their study, the researchers developed novel molecular tools.
“These molecular tools allow us to finely control the function of the centrosome to generate microtubules” explains Sebastian Dupraz.
In this way, its activity can be decreased or increased. The scientists showed in the mouse brains that the axon form independently of the centrosomal activity. However, neuronal migration is significantly influenced.
“A different mechanism is apparently responsible for the growth of the axon, the so-called acentrosomal formation of microtubules,” concludes Dupraz: “This will now become the subject of our future research.”
With their work, the scientists can now align two theories that previously contradicted each other: There were proponents of the theory that the centrosome plays a significant role in neuronal development and those who disputed it.
“For our study, we disentangled the two mechanisms that occur in neurons simultaneously,” says Stanislav Vinopal. “For the growth of the axon itself, we found that the centrosome is not necessary. For the process of neuronal migration, however, it plays a major role.”
The DZNE scientists’ discovery may help develop a molecular therapy for some inherited diseases, such as so-called developmental pachygyrias, that are linked to mutations of the centrosomal protein gamma-tubulin. Also in these disease phenotypes, axons are mostly intact, while neuronal migration is impaired.
“Presumably, the same molecular mechanism is behind these disorders, so a future therapy might focus on this point,” the DZNE researchers say.
Inhibition of Rho-kinase ameliorates decreased spine density in the medial prefrontal cortex and methamphetamine-induced cognitive dysfunction in mice carrying schizophrenia-associated mutations of the Arhgap10 gene
by Rinako Tanaka, Jingzhu Liao, Kazuhiro Hada, Daisuke Mori, Taku Nagai, Tetsuo Matsuzaki, Toshitaka Nabeshima, Kozo Kaibuchi, Norio Ozaki, Hiroyuki Mizoguchi, Kiyofumi Yamada in Pharmacological Research
A team from Nagoya University in Japan used the drug fasudil to reverse two common symptoms associated with schizophrenia: reduced density of pyramidal neurons and cognitive dysfunction associated with methamphetamine treatment.? Their findings, which were published in Pharmacological Research, suggest new therapeutic approaches for treating schizophrenia patients.
Genetic vulnerability is generally accepted to be involved in the development of schizophrenia. One of the key genetic factors involved is copy-number variation, a genetic trait in which people have different numbers of a particular gene. In particular, variations in the copy number of the ARHGAP10 gene are associated with symptoms of schizophrenia.
ARHGAP10 encodes a protein that is involved in the regulation of the Rho GTPase family of enzymes. Among these Rho GTPase family members, a few reports have implicated RhoA in schizophrenia. In the current research, the group theorized that some of the downstream factors of RhoA may be treatment targets. They identified Rho-associated kinase (ROCK), as a potential therapeutic target, since activation of the RhoA/ROCK signaling pathway stimulates many risk factors for schizophrenia.
When model mice with mutations in their ARHGAP10 gene are bred, they exhibit symptoms similar to those of human schizophrenia patients. Symptoms include altered spine density, methamphetamine-induced cognitive dysfunction, and activation of RhoA/ROCK signaling.
“ROCK signaling promotes spine shrinkage and destabilization,” said lead researcher Rinako Tanaka from Nagoya University Graduate School of Medicine. “This is important because cognitive impairment, such as that seen in schizophrenia, is known to be associated with spine morphology.”
A team led by the Nagoya University Graduate School of Medicine, in collaboration with Fujita Health University, used fasudil to inhibit ROCK in model mice with mutations in their ARHGAP10 gene to see if this improved symptoms. They found that treatment restored the density of pyramidal neurons in the medial prefrontal cortex, a part of the brain associated with attention and long-term memory. As a result, mice with methamphetamine-induced cognitive impairment treated with the drug also performed better on visual discrimination tests.
“Our findings clarify how ROCK contributes to the neuropathological changes in spine morphology and to the cognitive vulnerability to methamphetamine caused by schizophrenia-associated mutations in the ARHGAP10 gene,” Tanaka said. “Targeting Rho-kinase signaling may provide new therapeutic approaches for the treatment of schizophrenia patients, including those with ARHGAP10 gene mutations. Inhibitors of Rho kinase, such as fasudil, or those downstream of Rho kinase may be future therapeutic drugs for schizophrenia.”
3D In Vitro Blood‐Brain‐Barrier Model for Investigating Barrier Insults
by Wei Wei, Fernando Cardes, Andreas Hierlemann, Mario M. Modena in Advanced Science
Mario Modena is a postdoc working in the Bio Engineering Laboratory at ETH Zurich. If he were to explain his research on the blood-brain barrier — the wall that protects our central nervous system from harmful substances in the blood stream — to an 11-year-old, he would say: “This wall is important, because it stops the bad guys from getting into the brain.” If the brain is damaged or sick, he says, holes can appear in the wall. Sometimes, such holes can actually be useful, for example, for supplying the brain with urgently needed medicine. “So what we are trying to understand is how to maintain this wall, break through it and repair it again.”
This wall is also important from a medical perspective because many diseases of the central nervous system are linked to an injury to the blood-brain barrier. To discover how this barrier works, scientists often conduct experiments on live animals. In addition to such experiments being relatively expensive, animal cells may provide only part of the picture of what is going on in the human body. Moreover, there are some critics, who question the basic validity of animal testing. An alternative is to base experiments on human cells that have been cultivated in the laboratory.
The problem with many in-vitro models is that they recreate the blood-brain barrier in a relatively simplified way using blood-vessel-wall cells (endothelial cells). This approach fails to represent the complex structure of the human system and disregards, for instance, the communication between the various cell types. Furthermore, many of these models are static. In other words, the cells are floating in a suspension that is not moving, which implies that fluid flow or the shear stress the cells are exposed to in the body are not considered.
There are also dynamic in-vitro models that simulate flow conditions in the body, but the catch here is that the pumps they require make the experimental setup rather complicated. Alongside all these challenges, there is the problem of measurement: it is all but impossible to take high-resolution images of structural changes to the blood-brain barrier in real time while also measuring the barrier’s electrical resistance, both of which reflect barrier compactness and tightness.
If each of these challenges were a bird, Modena’s platform would be the proverbial stone that kills them all. Working under Andreas Hierlemann, Modena and his colleagues spent three and a half years developing the open-microfluidic 3D blood-brain barrier model.
To recreate the barrier, the research team took those cell types that naturally make up the blood-brain barrier — microvascular endothelial cells, human astrocytes and human pericytes — and combined them within a single platform.
“This strategy allowed us to almost fully replicate the 3D cell structure found in the human body,” Modena says. “But what’s really exceptional is that we can measure the barrier’s permeability while simultaneously mapping morphological changes to the barrier by means of high-resolution time-lapse microscopy.”
To facilitate this double act, the researchers deposited entirely transparent electrodes on glass coverslips on both sides of the barrier to measure its permeability, which is reflected in the electrical resistance across the cell barrier. Transparent electrodes offer a decisive advantage over other types of electrodes, which include metal films or wire structures that may interfere with optical detection and high-resolution microscopy.
To mimic the way fluid flows in the body, the researchers realized the microfluidic platform with fluid reservoirs at both ends on a kind of seesaw. Gravity then triggered the flow, which — in turn — generated shear force on the cells.
Hierlemann explains the benefit of this setup: “Since we are not using any pumps, we can experiment with multiple model systems simultaneously, for instance in an incubator, without increasing the setup complexity.”
In a study, published recently in the journal Advanced Science, the researchers presented and tested their new in vitro blood-brain barrier model. They subjected the barrier to oxygen-glucose deprivation, as happens when someone is having a stroke.
“These experiments allowed us to trigger rapid changes in the barrier and demonstrate the platform’s potential,” Modena says.
Through this study, Modena and his colleagues were able to do more than showing that their new platform is suitable for taking measurements. They also discovered that the barrier’s electrical resistance decreases even before it undergoes morphological changes that make it more permeable.
“This finding could prove relevant for future research,” Modena says. The team also observed that in control experiments using a static in-vitro model, the barrier was more permeable than in the new dynamic setup. “It is clear that the shear force, generated by the gravity-driven flow, promotes the formation of a denser barrier layer, which confirms how important flow is for representative in-vitro models” Modena says.
Modena and Hierlemann believe that their model will make it easier to detect which molecules stabilise the barrier, as well as to discover compounds and methods suitable for crossing it, which would be useful in the treatment of brain tumours. But Hierlemann notes that the model could also change the course of future in-vitro research:
“The advantage of our platform is that it is very easy to adapt to other endothelial cell models, where a combination of barrier-tightness measurements and high-resolution microscopy could pave the way to new research.”
Industry has manifested interest in the new the model. A pharmaceutical company is already in contact with the researchers.
Neuronal dynamics of the default mode network and anterior insular cortex: Intrinsic properties and modulation by salient stimuli
by Tzu-Hao Harry Chao, Byeongwook Lee, Li-Ming Hsu, Domenic Hayden Cerri, Wei-Ting Zhang, Tzu-Wen Winnie Wang, Srikanth Ryali, Vinod Menon, Yen-Yu Ian Shih in Science Advances
When we daydream or revisit memories, a large group of regions within our brain “lights up,” or becomes more active. It’s referred to as the Default Mode Network (DMN) because it is more active when the brain is not focused on the outside world.
Numerous brain disorders, including Alzheimer’s, attention-deficit/hyperactivity disorder, and mood disorders, have been linked to issues with the DMN. However, the neurophysiological basis of the DMN is not well understood.
Neuroimaging techniques, like functional magnetic resonance imaging (fMRI), are not able to directly measure neuronal activity. To address this knowledge gap, a research team led by Ian Shih, PhD, professor and vice chair of the Department of Neurology and associate director of the Biomedical Research Imaging Center, has created a novel experimental platform that is able to optically record local neuronal activity during brain-wide fMRI in rodents.
“We hope that this work will pave the way for future translational studies aimed at controlling large-scale brain networks,” said Shih. “This could help design network-based treatment regimens for many neurological and neuropsychiatric disorders.”
The study, which was published in the journal Science Advances, examined the dynamic activity of DMN-related brain regions and analyzed them with a variety of computational approaches.
The DMN is one of our brain’s large-scale brain networks. When we first learn about the brain, we are taught that each part of the brain has a distinct function. But the reality is that many brain areas activate and deactivate together during behavior and cognition, and form large-scale brain networks, much like a team.
Neuroscientists are becoming more interested in these large-scale networks as they learn that certain cognitive tasks are dependent upon “functionally connected” brain regions. When a person is awake and at rest, like when they are daydreaming, retrieving memories, or envisioning the future, the DMN is active.
However, it is challenging to obtain the neuronal data necessary to understand dynamic DMN activity in human subjects, so Shih and team turned to an animal model to study the network, in which putative DMN-related brain regions have been identified.
“We used a rodent model, where genetically encoded calcium sensors were expressed in neurons,” said first author Tzu-Hao Harry Chao, PhD, who built and validated this experimental platform in the Shih lab. “This allowed us to record neuronal activity in multiple DMN-related brain regions by detecting changes in fluorescence via optical fibers without interfering with the measurement of fMRI signals.”
Fiber photometry uses fiber optics to deliver certain wavelengths of light to excite fluorescent proteins responsive to that wavelength and record activity-dependent light emission. Through this process, scientists can directly measure activity from specific population of cells or neurochemicals within a specified location of the brain.
Using this novel experimental platform, Chao and colleagues demonstrated that activation of one area of the brain — the anterior insular cortex — is associated with suppressing, or “turning off,” the Default Mode Network.
In the human brain, the insular cortex is found in the cortex and is “insulated” by the frontal, parietal, and temporal lobes. The insula is responsible for several important functions in the brain, including processing our five senses, controlling hand-eye coordination, and self-awareness. The insula also plays a critical role in social and addiction-related behaviors.
“This is important neuronal evidence highlighting the role of the anterior insular cortex in controlling DMN activity,” Shih explained.
In collaboration with Vinod Menon, PhD, another senior author and professor of the Department of Psychiatry & Behavioral Sciences at Stanford University, the research team further used advanced computational approaches to identify the brain states and information flow during these conditions.
The team also discovered that the prelimbic area of the rodent cortex alternates its synchronization with the DMN and anterior insular cortex, which suggests that the prelimbic cortex in the rodent brain could also play a role in the salience network — another large-scale brain network important for attention, sensory processing, and goal-directed behavior.
Prolonged microgravity induces reversible and persistent changes on human cerebral connectivity
by Steven Jillings, Ekaterina Pechenkova, Elena Tomilovskaya, Ilya Rukavishnikov, Ben Jeurissen, Angelique Van Ombergen, Inna Nosikova, Alena Rumshiskaya, Liudmila Litvinova, Jitka Annen, Chloë De Laet, Catho Schoenmaekers, Jan Sijbers, Victor Petrovichev, Stefan Sunaert, Paul M. Parizel, Valentin Sinitsyn, Peter zu Eulenburg, Steven Laureys, Athena Demertzi, Floris L. Wuyts in Communications Biology
Scientists of the University of Antwerp and University of Liège have found how the human brain changes and adapts to weightlessness, after being in space for 6 months. Some of the changes turned out to be lasting — even after 8 months back on Earth. Raphaël Liégeois, soon to be the third Belgian in space, acknowledges the importance of the research, “to prepare the new generation of astronauts for longer missions.”
A child who learns not to drop a glass on the floor, or a tennis player predicting the course of an incoming ball to hit it accurately are examples of how the brain incorporates the physical laws of gravity to optimally function on Earth. Astronauts who go to space reside in a weightless environment, where the brain’s rules about gravity are no longer applicable. A new study on brain function in cosmonauts has revealed how the brain’s organization is changed after a six-month mission to the International Space Station (ISS), demonstrating the adaptation that is required to live in weightlessness.
The University of Antwerp has been leading this BRAIN-DTI scientific project through the European Space Agency. Magnetic resonance imaging (MRI) data were taken from 14 astronaut brains before and several times after their mission to space. Using a special MRI technique, the researchers collected the astronauts’ brain data in a resting condition, hence without having them engage in a specific task. This resting-state functional MRI technique enabled the researchers to investigate the brain’s default state and to find out whether this changes or not after long-duration spaceflight.
In collaboration with the University of Liège, recent analyses of the brain’s activity at rest revealed how functional connectivity, a marker of how activity in some brain areas is correlated with the activity in others, changes in specific regions.
“We found that connectivity was altered after spaceflight in regions which support the integration of different types of information, rather than dealing with only one type each time, such as visual, auditory, or movement information’, say Steven Jillings and Floris Wuyts (University of Antwerp). “Moreover, we found that some of these altered communication patterns were retained throughout 8 months of being back on Earth. At the same time, some brain changes returned to the level of how the areas were functioning before the space mission.”
Both scenarios of changes are plausible: retained changes in brain communication may indicate a learning effect, while transient changes may indicate more acute adaptation to changed gravity levels.
“This dataset is so special as their participants themselves. Back in 2016, we were historically the first to show how spaceflight may affect brain function on a single cosmonaut. Some years later we are now in a unique position to investigate the brains of more astronauts, several times. Therefore, we are deciphering the potential of the human brain all the more in confidence,” says Dr. Athena Demertzi (GIGA Institute, University of Liège), co-supervisor of this this work.
“Understanding physiological and behavioral changes triggered by weightlessness is key to plan human space exploration. Therefore, mapping changes of brain function using neuroimaging techniques as done in this work is an important step to prepare the new generation of astronauts for longer missions,” comments Raphaël Liégeois, Doctor of Engineering Science (ULiège) with a Thesis in the field of Neuroscience, future ESA Astronaut.
The researchers are excited with the results, though they know it is only the first step in pursuing our understanding of brain communication changes after space travel. For example, we still need to investigate what the exact behavioural consequence is for these brain communication changes, we need to understand whether longer time spent in outer space might influence these observations, and whether brain characteristics may be helpful in selecting future astronauts or monitoring them during and after space travel.
Emergent low-frequency activity in cortico-cerebellar networks with motor skill learning
by Pierson J. Fleischer, Aamir Abbasi, Andrew W. Fealy, Nathan P. Danielsen, Ramneet Sandhu, Philip R. Raj, Tanuj Gulati in eneuro
The findings, published in the peer-reviewed journal eNeuro, provide insight into the neural mechanisms of motor skill learning that can help lead to more effective brain-stimulation therapies for patients experiencing motor disability after a stroke.
“One of the main complaints from stroke patients is that they cannot complete the grasping action,” said Tanuj Gulati, PhD, assistant professor of Neurology and Biomedical Sciences’ Center for Neural Science and Medicine at Cedars-Sinai and senior and corresponding author of the study. “Many patients may be able to reach for the target they want with some recovery, but they are not able to grasp it accurately. So, we are looking to understand how the brain generates movement and learns new dexterous/fine motor skills so we can potentially develop novel treatment strategies to repair these disabilities.”
To better understand changes in the brain during the course of motor learning, investigators looked at brain physiological activity in the motor cortex and the cerebellum in rats as they practiced a skilled reaching task.
The motor cortex, which is the chief driver of all movement, controls arm movement by recruiting a variety of targets in the nervous system. One fundamental projection of the motor cortex is to the cerebellum, the part of the brain that holds more than half the neurons of the entire body.
However, the activity between the motor cortex and the cerebellum that emerges as a fine motor skill is learned is not widely understood.
Using healthy rats, investigators recorded from the motor cortex and the cerebellar cortex chronically as the animals were trained for five days to perform a fine motor task where they reached for a sugar pellet placed at a distance from them. Rats had to reach for and grab the pellet and retrieve it for the successful completion of the trial.
The team then compared the neural activity from the early days of training to the late days to see what changed in the brain as the rodents gained proficiency in the task.
The investigators discovered that as the rats became proficient in the task, they developed synchronous low-frequency oscillatory activity in the two areas that were recorded that emerged across the motor cortex and cerebellum networks with skill consolidation. This activity also coordinated neural spiking in both these regions for successful reach-to-grasp task execution.
Interestingly, the team did not observe the emergence of low-frequency oscillatory activity in the rats that did not gain expertise in the task within five days.
“We were able to show this activity is a marker of skill learning,” said Gulati. “Understanding these mechanisms in a healthy brain is an important precursor to check if similar activity is weakened in the brain after a stroke and can serve as a biomarker during recovery. This activity can then be a target for electric stimulation approaches to promote motor recovery after a stroke.”
Gulati is now working to repeat this work in stroke rats to see if this coordinated low-frequency activity in the motor cortex and cerebellum becomes weak in the animals after a stroke and resurges as the rats recover their reaching and grasping abilities.
Individual variability in performance reflects selectivity of the multiple demand network among children and adults
by Elana Schettini, Kelly J. Hiersche, Zeynep M. Saygin in The Journal of Neuroscience
Children as young as 4 years old show evidence of a network in the brain found in adults that tackles difficult cognitive problems, a new study found.
The multiple-demand network helps people focus their attention, juggle several things in memory at the same time, and solve difficult problems like those involving math.
And while this network is not fully developed in kids, the study showed it operated similarly as it does in adults, said Zeynep Saygin, senior author of the study and assistant professor of psychology at The Ohio State University.
The study involved adults and 4- to 12-year-old children whose brains were scanned in an fMRI while they tried to complete a difficult task.
“We found that the multiple demand network was a distinct network even in young children, and was separate from the language network, just as it is in adults,” Saygin said. “That was something that wasn’t known for sure. One alternative would have been that it takes time for these separate networks in the brain to differentiate themselves in children, but that’s not what we found.”
The study was led by Elana Schettini, a graduate student in psychology at Ohio State, and the results were published online recently in the Journal of Neuroscience. Ohio State graduate student Kelly Hiersche was also a co-author. The results may help identify disruptions in the neurodevelopment of cognitive control among clinical samples, such as children struggling with ADHD, conduct disorder, or brain injuries, which could eventually inform treatment development.
“By identifying typical variability in the relationship between neural activation and performance on task, we can gain a better understanding of what is considered normal vs. abnormal” Schettini said.
The study involved 44 adults 18 to 38 years old and 37 children aged 4 to 12.
While being scanned in the fMRI, study participants were given a relatively difficult task: They were shown a series of grids containing nine to 12 squares, some of which were blue. They were then shown two grids, and they had to choose which one matched the sequence of blue squares they had seen in earlier grids. Children were given easier trials than adults.
The same participants also completed a language task where they listened to meaningful sentences and control conditions. In adults, the language brain network is spatially adjacent to, but separate from, the multiple demand network. But children’s language skills are also still developing and so it was unclear whether the multiple demand network also supports this skill as it develops.
Results showed that the same area of the brain — the multiple demand network, located in the frontal and parietal cortices — was activated in both children and adults when they completed the challenging task, and not at all activated for the language task.
There were reasons to expect that kids wouldn’t have a multiple demand network similar to adults, Saygin said.
“We know that children aren’t always good at knowing what to focus on, they are distracted easily, and they don’t always do well when presented with difficult problems. So it wasn’t a given that they would be using the same multiple demand network that adults use,” she said. “But even in 4-year-olds this network is pretty robust and is very distinct from the language network.”
There were some differences from adults. The response magnitude seen in the brain was smaller in children as they tried to solve the task, indicating it takes years for the brain to mature and “ramp up” to adult levels, she said.
But even in children, multiple demand brain activation reflected how hard they tried and how well they performed during the task, regardless of age; individual variability in performance was reflected in the brain activation at all ages.
“The findings give us a better understanding of how high-level cognition emerges in humans and could help us design interventions for when people have issues with cognitive control,” Saygin said.
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