NS/ Researchers develop an algorithm to track mental states through the skin
Neuroscience biweekly vol. 64, 3rd August — 17th August
TL;DR
- Biomedical engineers have developed a way to measure mental activity using electrodermal activity (EDA) — an electrical phenomenon of the skin that is influenced by brain activity related to emotional status. They describe a novel inference engine that can monitor brain activity through the skin in real-time with high scalability and accuracy.
- The discovery of how to shift damaged brain cells from a diseased state into a healthy one presents a potential new path to treating Alzheimer’s and other forms of dementia, according to a new study from researchers at UC San Francisco.
- It’s no surprise that hard physical labor wears you out, but what about hard mental labor? Sitting around thinking hard for hours makes one feel worn out, too. Now, researchers have new evidence to explain why this is, and, based on their findings, the reason you feel mentally exhausted (as opposed to drowsy) from intense thinking isn’t all in your head.
- A team has found that electrical stimulation of the body combined with sound activates the brain’s somatosensory cortex, increasing the potential for using the technique to treat chronic pain and other sensory disorders.
- Investigators have created the most bio-realistic and complex computer models of individual brain cells — in unparalleled quantity. Their research details how these models could one day answer questions about neurological disorders — and even human intellect — that aren’t possible to explore through biological experiments.
- The traditional tests and grades that educators have long used may measure learning less accurately than scans of the brain, according to a new study published in Science Advances. The paper, authored by a team of researchers from seven universities and led by Georgetown neuroscientists, could not only upend how educators craft curricula, but reveals a hidden link in the human mind.
- Researchers have identified a molecular pathway responsible for the spread of glioblastoma to surrounding tissue in the brain, as well as an existing drug that curbed tumor growth in animal models. The findings have led to a clinical trial that could offer new hope to patients with glioblastoma, the most common form of brain cancer in adults that kills hundreds of thousands of people worldwide each year.
- A new study into the neurons found in the earliest-diverging animal lineages reveals key clues about the form of the most ancestral nervous system, and how neurons first evolved.
- After 20 years of searching for a cure for tinnitus, researchers at the University of Auckland are excited by ‘encouraging results’ from a clinical trial of a mobile-phone-based therapy. The study randomised 61 patients to one of two treatments, the prototype of the new ‘digital polytherapeutic’ or a popular self-help app producing white noise.
- New study shows that microglia cells ‘listen in’ to neighboring neurons and change to match them.
- And more!
Neuroscience market
The global neuroscience market size was valued at USD 28.4 billion in 2016 and it is expected to reach USD 38.9 billion by 2027.
Latest news and research
Physiological characterization of electrodermal activity enables scalable near real-time autonomic nervous system activation inference
by Rafiul Amin, Rose T. Faghih in PLOS Computational Biology
Researchers at NYU Tandon have reached a key milestone in their quest to develop wearable technology that manages to measure key brain mechanisms through the skin.
Rose Faghih, Associate Professor of Biomedical Engineering, has been working for the last seven years on a technology that can measure mental activity using electrodermal activity (EDA) — an electrical phenomenon of the skin that is influenced by brain activity related to emotional status. Internal stresses, whether caused by pain, exhaustion, or a particularly packed schedule, can cause changes in the EDA — changes that are directly correlated to mental states.
The overarching goal — a Multimodal Intelligent Noninvasive brain state Decoder for Wearable AdapTive Closed-loop arcHitectures, or MINDWATCH, as Faghih calls it — would act as a way to monitor a wearer’s mental state, and offer nudges that would help them revert back to a more neutral state of mind. For example, if a person was experiencing a particularly severe bout of work-related stress, the MINDWATCH could pick up on this and automatically play some relaxing music.
Now Faghih — along with Rafiul Amin, her former PhD student — has accomplished a crucial task required for monitoring this information. For the first time, they have developed a novel inference engine that can monitor brain activity through the skin in real time with high scalability and accuracy. The results are featured in a new paper, “Physiological Characterization of Electrodermal Activity Enables Scalable Near Real-Time Autonomic Nervous System Activation Inference,” published in PLOS Computational Biology.
“Inferring autonomic nervous system activation from wearable devices in real-time opens new opportunities for monitoring and improving mental health and cognitive engagement,” according to Faghih.
Previous methods measuring sympathetic nervous system activation through the skin took minutes, which is not practical for wearable devices. While her earlier work focused on inferring brain activity through sweat activation and other factors, the new study additionally models the sweat glands themselves. The model includes a 3D state-space representation of the direct secretion of sweat via pore opening, as well as diffusion followed by corresponding evaporation and reabsorption. This detailed model of the glands provides exceptional insight into inferring the brain activity.
The new model was run on data from 26 healthy individuals. The researchers showed that they can decipher brain signals with high reliability. Additionally, the computational power requirement of their new algorithm is minimal and can obtain brain and physiological insights within a few seconds whereas another previous approach would take minutes. This means that small, wearable monitoring technology capable of incredible speed, high scalability, and extraordinary reliability is within reach.
The broader impact and applications of the methodology includes performance monitoring, mental health monitoring, measuring pain and cognitive stress. Mental health tracking can help better manage autism, post-traumatic stress disorders, excessive irritability, suicidal tendency, and more. Performance tracking and cognitive stress tracking can help improve individual productivity and quality of life.
“One’s performance changes based on their cognitive engagement and arousal levels.” says Faghih. For example, very low or very high levels of arousal can result in poor performance. Hence, it is expected that. Ultimately, researchers can utilize the inferred autonomic nervous system activation and decoded arousal to develop interventions for improving productivity.”
One example application of this method is early diagnosis of disorders like diabetic neuropathy. Small nerves transmit brain stimulation to many parts of the body, including those linked to skin conductance response. To track the received brain activity, EDA may be measured and monitored on a regular basis in neuropathy-prone skin areas of the body. If a skin area has neuropathy (i.e., tiny nerves have been damaged), the brain will not activate that area. By monitoring changes, doctors can see how a condition like diabetic neuropathy progresses, and can lead to changes in treatment plans.
Another example is a newborn patient in extreme pain following a surgical procedure, who cannot convey their degree of suffering. Doctors may use EDA recordings and infer brain activity to assess how much pain the infant patient is in and intervene as needed.
For Faghih, this work could represent a breakthrough for mental health care. Monitoring the mental status of vulnerable people could help them get more effective care and prevent severe consequences from declining mental health or swings in mood.
Her team is now working on ways to incorporate the model into wearables, including the elimination of informational “noise” caused by factors like robust movement and exercise, as well as seeking potential partnerships to design and manufacture the devices that would carry the algorithm.
A neuro-metabolic account of why daylong cognitive work alters the control of economic decisions
by Antonius Wiehler, Francesca Branzoli, Isaac Adanyeguh, Fanny Mochel, Mathias Pessiglione in Current Biology
It’s no surprise that hard physical labor wears you out, but what about hard mental labor? Sitting around thinking hard for hours makes one feel worn out, too. Now, researchers have new evidence to explain why this is, and, based on their findings, the reason you feel mentally exhausted (as opposed to drowsy) from intense thinking isn’t all in your head.
Their studies, reported in Current Biology on August 11, show that when intense cognitive work is prolonged for several hours, it causes potentially toxic byproducts to build up in the part of the brain known as the prefrontal cortex. This in turn alters your control over decisions, so you shift toward low-cost actions requiring no effort or waiting as cognitive fatigue sets in, the researchers explain.
“Influential theories suggested that fatigue is a sort of illusion cooked up by the brain to make us stop whatever we are doing and turn to a more gratifying activity,” says Mathias Pessiglione of Pitié-Salpêtrière University in Paris, France. “But our findings show that cognitive work results in a true functional alteration — accumulation of noxious substances — so fatigue would indeed be a signal that makes us stop working but for a different purpose: to preserve the integrity of brain functioning.”
Pessiglione and colleagues including first author of the study Antonius Wiehler wanted to understand what mental fatigue really is. While machines can compute continuously, the brain can’t. They wanted to find out why. They suspected the reason had to do with the need to recycle potentially toxic substances that arise from neural activity.
To look for evidence of this, they used magnetic resonance spectroscopy (MRS) to monitor brain chemistry over the course of a workday. They looked at two groups of people: those who needed to think hard and those who had relatively easier cognitive tasks.
They saw signs of fatigue, including reduced pupil dilation, only in the group doing hard work. Those in that group also showed in their choices a shift toward options proposing rewards at short delay with little effort. Critically, they also had higher levels of glutamate in synapses of the brain’s prefrontal cortex. Together with earlier evidence, the authors say it supports the notion that glutamate accumulation makes further activation of the prefrontal cortex more costly, such that cognitive control is more difficult after a mentally tough workday.
So, is there some way around this limitation of our brain’s ability to think hard?
“Not really, I’m afraid,” Pessiglione said. “I would employ good old recipes: rest and sleep! There is good evidence that glutamate is eliminated from synapses during sleep.”
There may be other practical implications. For example, the researchers say, monitoring of prefrontal metabolites could help to detect severe mental fatigue. Such an ability may help adjust work agendas to avoid burnout. He also advises people to avoid making important decisions when they’re tired.
In future studies, they hope to learn why the prefrontal cortex seems especially susceptible to glutamate accumulation and fatigue. They’re also curious to learn whether the same markers of fatigue in the brain may predict recovery from health conditions, such as depression or cancer.
A CRISPRi/a platform in human iPSC-derived microglia uncovers regulators of disease states
by Nina M. Dräger, Sydney M. Sattler, Cindy Tzu-Ling Huang, Olivia M. Teter, Kun Leng, Sayed Hadi Hashemi, Jason Hong, Giovanni Aviles, Claire D. Clelland, Lihong Zhan, Joe C. Udeochu, Lay Kodama, Andrew B. Singleton, Mike A. Nalls, Justin Ichida, Michael E. Ward, Faraz Faghri, Li Gan, Martin Kampmann in Nature Neuroscience
The discovery of how to shift damaged brain cells from a diseased state into a healthy one presents a potential new path to treating Alzheimer’s and other forms of dementia, according to a new study from researchers at UC San Francisco.
The research focuses on microglia, cells that stabilize the brain by clearing out damaged neurons and the protein plaques often associated with dementia and other brain diseases.
These cells are understudied, despite the fact that changes in them are known to play a significant role Alzheimer’s and other brain diseases, said Martin Kampmann, PhD, senior author of the study, which appears Aug. 11 in Nature Neuroscience.
“Now, using a new CRISPR method we developed, we can uncover how to actually control these microglia, to get them to stop doing toxic things and go back to carrying out their vitally important cleaning jobs,” he said. “This capability presents the opportunity for an entirely new type of therapeutic approach.”
Most of the genes known to increase the risk for Alzheimer’s disease act through microglial cells. Thus, these cells have a significant impact on how such neurodegenerative diseases play out, said Kampmann.
Microglia act as the brain’s immune system. Ordinary immune cells can’t cross the blood-brain barrier, so it’s the task of healthy microglia to clear out waste and toxins, keeping neurons functioning at their best. When microglia start losing their way, the result can be brain inflammation and damage to neurons and the networks they form.
Under some conditions, for example, microglia will start removing synapses between neurons. While this is a normal part of brain development in a person’s childhood and adolescent years, it can have disastrous effects in the adult brain.
Over the past five years or so, many studies have observed and profiled these varying microglial states but haven’t been able to characterize the genetics behind them.
Kampmann and his team wanted to identify exactly which genes are involved in specific states of microglial activity, and how each of those states are regulated. With that knowledge, they could then flip genes on and off, setting wayward cells back on the right track.
Accomplishing that task required surmount fundamental obstacles that have prevented researchers from controlling gene expression in these cells. For example, microglia are very resistant to the most common CRISPR technique, which involves getting the desired genetic material into the cell by using a virus to deliver it.
To overcome this, Kampmann’s team coaxed stem cells donated by human volunteers to become microglia and confirmed that these cells function like their ordinary human counterparts. The team then developed a new platform that combines a form of CRISPR, which enables researchers to turn individual genes on and off — and which Kampmann had a significant hand in developing — with readouts of data that indicate functions and states of individual microglia cells.
Through this analysis, Kampmann and his team pinpointed genes that effect the cell’s ability to survive and proliferate, how actively a cell produces inflammatory substances, and how aggressively a cell prunes synapses.
And because the scientists had determined which genes control those activities, they were able to reset the genes and flip the diseased cell to a healthy state.
Armed with this new technique, Kampmann plans to investigate how to control the relevant states of microglia, by targeting the cells with existing pharmaceutical molecules and testing them in preclinical models. He hopes to find specific molecules that act on the genes necessary to nudge diseased cells back to a healthy state.
Kampmann said that once the right genes are flipped, it’s likely that the “repaired,” microglia will resume their responsibilities, removing plaques associated with neurodegenerative disease and protecting synapses rather than taking them apart.
“Our study provides a blueprint for a new approach to treatment,” he said. “It’s a bit of a holy grail.”
Topographic and widespread auditory modulation of the somatosensory cortex: potential for bimodal sound and body stimulation for pain treatment
by Cory D Gloeckner, Jian C Nocon, Hubert H Lim in Journal of Neural Engineering
A University of Minnesota Twin Cities-led team has found that electrical stimulation of the body combined with sound activates the brain’s somatosensory or “tactile” cortex, increasing the potential for using the technique to treat chronic pain and other sensory disorders. The researchers tested the non-invasive technique on animals and are planning clinical trials on humans in the near future.
During the experiments, the researchers played broadband sound while electrically stimulating different parts of the body in guinea pigs. They found that the combination of the two activated neurons in the brain’s somatosensory cortex, which is responsible for touch and pain sensations throughout the body.
While the researchers used needle stimulation in their experiments, one could achieve similar results using electrical stimulation devices, such as transcutaneous electrical nerve stimulation (TENS) units, which are widely available for anyone to buy at pharmacies and stores. The researchers hope that their findings will lead to a treatment for chronic pain that’s safer and more accessible than drug approaches.
“Chronic pain is a huge issue for a lot of people, and for most, it’s not sufficiently treatable,” said Cory Gloeckner, lead author on the paper, a 2017 Ph.D. alumnus of the University of Minnesota Twin Cities Department of Biomedical Engineering, and an assistant professor at John Carroll University. “Right now, one of the ways that we try to treat pain is opioids, and we all know that doesn’t work out well for many people. This, on the other hand, is a non-invasive, simple application. It’s not some expensive medical device that you have to buy in order to treat your pain. It’s something that we think would be available to pretty much anyone because of its low cost and simplicity.”
The researchers plan to continue investigating this “multimodal” approach to treating different neurological conditions, potentially integrating music therapy in the future to see how they can further modify the somatosensory cortex.
“A lot of people have been using acupuncture or electrical stimulation — non-invasive or invasive — to try to alter brain activity for pain,” said Hubert Lim, senior author on the paper and a professor in the University of Minnesota Twin Cities Department of Biomedical Engineering and Department of Otolaryngology. “Our research shows that when you combine this with sound, the brain lights up even more.”
Lim said this opens up a whole new field of using this bimodal and multimodal stimulation for treating diseases.
“It’s odd to think about using sound to treat pain, but if you think about what institutes like the University of Minnesota’s Center for Spirituality and Healing or the NIH’s National Center for Complementary and Integrative Health are doing, they’re looking at music therapy and combining other modalities with the traditional methods to be able to enhance healing of these types of conditions,” Lim said. “This research gives us a new, structured framework for doing that moving forward.”
Pyramidal neuron subtype diversity governs microglia states in the neocortex
by Jeffrey A. Stogsdill, Kwanho Kim, Loïc Binan, Samouil L. Farhi, Joshua Z. Levin, Paola Arlotta in Nature
From everyday actions like walking and talking to feats of athletic or academic excellence, the brain is constantly acquiring and seamlessly processing information to produce these incredible behaviors. The process requires a whole orchestra of cells listening to each other and tuning their functions to harmonize together. One of the remaining, most fundamental questions in neuroscience asks how cells in the brain move, interact, and coordinate with each other to produce these activities.
In the brain, this cellular symphony includes not only neurons, but cells that normally play a role in defending the body against pathogens. One group are tiny immune cells called microglia, which researchers are increasingly learning play oversized roles in brain function, health, and disease. The cells are also gaining increased attention for their roles in assembling and maintaining neural circuits, and how they are able to change their molecular identity to match their environment. To neuroscientists, the mystery has long been how they make this change.
In a new report in Nature, a team of researchers from the lab of Golub Family Professor of Stem Cell and Regenerative Biology Paola Arlotta and from the Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard come closer to answering this question. The paper shows that microglia cells “listen in” to neighboring neurons and change their molecular state to match them.
“When they were first discovered, microglia were assumed to be simply scavengers, cleaning up cell debris and helping to fight off pathogens,” said Jeffery Stogsdill, who led the study as a postdoctoral researcher in the Arlotta Lab. “Now we know that microglia can interact with neurons in very sophisticated ways that can affect neuron function.”
This discovery could one day open the door for lines of research that can target the communications between microglia and their neuron partners with pinpoint accuracy (disorders like autism and schizophrenia arise when these communications between cells go awry).
“You would no longer have to treat, for instance, microglia as one blanket cell type when trying to affect the brain,” Stogsdill continues. “We can target very specific states, or we can target very specific subtypes of neurons with the ability to change specific states of microglia. It allows us to have high-level granularity.”
The study provides unique insight into how different cell types work together in harmony.
“What we’re discovering here are the rules by which different cell types in the brain talk to each other and influence each other to ultimately be able to do more together,” said senior author Arlotta, an institute member at the Broad.
In the paper, the scientists describe how neurons train microglia to work with them when they first meet, early in the life of the brain. The group found that during the formation of the cerebral cortex — a part of the brain responsible for skilled motor function, sensory perception, and congnition — different types of neurons influence the number and molecular state of nearby microglia in their own unique ways.
“These different types of cortical neurons recruit different numbers of microglia,” Stogsdill said. “They then pattern those microglia to tell them exactly what type they need to be.”
The cerebral cortex is organized into layers with different neuron types residing in each one. The researchers used genetic profiling methods to examine the microglia in the different layers and discovered that microglia varied in number and molecular state depending on the layer where they were found. The team then changed the composition of neuron types in these layers and found that they could influence the distribution of the different microglial states. The microglia matched the types of neurons in the new locations, confirming that the neurons were influencing them.
The research team then built a molecular atlas that outlines the communication between neurons and microglia. The team analyzed their profiling data to find pairs of interacting proteins expressed by the different microglial states and their neuron partners. Such a molecular atlas could enable future research into the functional roles of these interactions and possible targets for therapeutic intervention. They plan to start by explaining exactly what the differences and functional distinctions are among the microglia in the different layers.
“We know that microglia can affect the function of the neural circuit, and now we know that neurons can recruit specific types of microglia to their neighborhood,” Arlotta said. “It’s a fascinating idea that neurons can reshape their environment to help fine-tune their own circuit function.”
Single-neuron models linking electrophysiology, morphology, and transcriptomics across cortical cell types
by Anirban Nandi, Thomas Chartrand, Werner Van Geit, Anatoly Buchin, Zizhen Yao, Soo Yeun Lee, Yina Wei, Brian Kalmbach, Brian Lee, Ed Lein, Jim Berg, Uygar Sümbül, Christof Koch, Bosiljka Tasic, Costas A. Anastassiou in Cell Reports,
Cedars-Sinai investigators have created the most bio-realistic and complex computer models of individual brain cells — in unparalleled quantity. Their research, published today in the peer-reviewed journal Cell Reports, details how these models could one day answer questions about neurological disorders — and even human intellect — that aren’t possible to explore through biological experiments.
“These models capture the shape, timing and speed of the electrical signals that neurons fire in order to communicate with each other, which is considered the basis of brain function,” said Costas Anastassiou, PhD, a research scientist in the Department of Neurosurgery at Cedars-Sinai, and senior author of the study. “This lets us replicate brain activity at the single-cell level.”
The models are the first to combine data sets from different types of laboratory experiments to present a complete picture of the electrical, genetic and biological activity of single neurons. The models can be used to test theories that would require dozens of experiments to examine in the lab, Anastassiou said.
“Imagine that you wanted to investigate how 50 different genes affect a cell’s biological processes,” Anastassiou said. “You would need to create a separate experiment to ‘knock out’ each gene and see what happens. With our computational models, we will be able to change the recipes of these gene markers for as many genes as we like and predict what will happen.”
Another advantage of the models is that they allow researchers to completely control experimental conditions. This opens the possibility of establishing that one parameter, such as a protein expressed by a neuron, causes a change in the cell or a disease condition, such as epileptic seizures, Anastassiou said. In the lab, investigators can often show an association, but it is difficult to prove a cause.
“In laboratory experiments, the researcher doesn’t control everything,” Anastassiou said. “Biology controls a lot. But in a computational simulation, all the parameters are under the creator’s control. In a model, I can change one parameter and see how it affects another, something that is very hard to do in a biological experiment.”
To create their models, Anastassiou and his team from the Anastassiou Lab — members of the Departments of Neurology and Neurosurgery, the Board of Governors Regenerative Medicine Institute and the Center for Neural Science and Medicine at Cedars-Sinai, used two different sets of data on the mouse primary visual cortex, the area of the brain that processes information coming from the eyes.
The first data set presented complete genetic pictures of tens of thousands of single cells. The second linked the electrical responses and physical characteristics of 230 cells from the same brain region. The investigators used machine learning to integrate these two datasets and create bio-realistic models of 9,200 single neurons and their electrical activity.
“This work represents a significant advancement in high-performance computing,” said Keith L. Black, MD, chair of the Department of Neurosurgery and the Ruth and Lawrence Harvey Chair in Neuroscience at Cedars-Sinai. “It also gives researchers the ability to search for relationships within and between cell types and to glean a deeper understanding of the function of cell types in the brain.”
The study was conducted in collaboration with the Allen Institute for Brain Science in Seattle, which also provided data.
“This work led by Dr. Anastassiou fits in well with Cedars-Sinai’s dedication to bringing together mathematics, statistics, and computer science with technology to address all the important questions in biomedical research and healthcare,” said Jason Moore, PhD, chair of the Department of Computational Biomedicine. “Ultimately, this computational direction will help us understand the deepest mysteries of the human brain.”
Anastassiou and his team are next working to create computational models of human cells to study brain function and disease in humans.
Mass spectrometry of short peptides reveals common features of metazoan peptidergic neurons
by Eisuke Hayakawa, Christine Guzman, Osamu Horiguchi, Chihiro Kawano, Akira Shiraishi, Kurato Mohri, Mei-Fang Lin, Ryotaro Nakamura, Ryo Nakamura, Erina Kawai, Shinya Komoto, Kei Jokura, Kogiku Shiba, Shuji Shigenobu, Honoo Satake, Kazuo Inaba, Hiroshi Watanabe in Nature Ecology & Evolution
Neurons, the specialized cells of the nervous system, are possibly the most complicated cell type ever to have evolved. In humans, these cells are capable of processing and transmitting vast sums of information. But how such complicated cells first came about remains a long-standing debate.
Now, scientists in Japan have revealed the type of messenger — molecules that carry signals from one cell to another — that likely functioned in the most ancestral nervous system.
The study also revealed key similarities between the nervous system of two early-diverging animal lineages — the lineage of jellyfish and anemones (also called cnidarians) and that of comb jellies (ctenophores), reigniting an earlier hypothesis that neurons only evolved once.
Despite their supposed simplicity, very little is known about the nervous system of ancient animals. Out of the four animal lineages that branched off before the rise of more complex animals, only comb jellies (the first ancient lineage to diverge) and cnidarians (the last ancient lineage to diverge) are known to possess neurons. But the uniqueness of the comb jellies nervous system compared to that seen in cnidarians and more complex animals, and the absence of neurons in the two lineages that diverged in between, led some scientists to hypothesize that neurons evolved twice.
But Professor Watanabe, who leads the Evolutionary Neurobiology Unit at the Okinawa Institute of Science and Technology (OIST), remained unconvinced.
“Indeed, comb jellies lack a lot of neural proteins that we see in more evolved animal lineages,” he said. “But for me, a lack of these proteins isn’t enough evidence for two independent neuron origins.”
In his study, Prof. Watanabe focused on an ancient and diverse group of neural messengers. Called neuropeptides, these short peptide chains are first synthesized in neurons as a long peptide chain, before being cleaved by digestive enzymes into many short peptides. They are the major form of messenger found in cnidarians, and also play a role in neural communication in humans, and other complex animals.
However, past research that has attempted to find similar neuropeptides in comb jellies has been unsuccessful. The main problem, explained Prof. Watanabe, is that the mature short peptides are encoded by only short sequences of DNA, and mutate frequently in these ancient lineages, making DNA comparisons too difficult. While artificial intelligence has identified potential peptides, these have not yet been experimentally validated.
So, Prof. Watanabe’s research team approached the problem in a new direction. They extracted peptides from sponges, cnidarians, and comb jellies and used mass spectrometry to search for short peptides. The team was able to find 28 short peptides in cnidarians and comb jellies and determine their amino acid sequences.
Now knowing their structures, the researchers visualized the short peptides under a fluorescent microscope, allowing them to see which cells were produced in both cnidarians and comb jellies.
In comb jellies, they found that one type of neuropeptide-expressing cell looked similar to classic neurons, with thin projections called neurites extending out from the cell.
But the short peptides were also produced in the second type of cell that lacked neurites. The researchers suspect these could be an early version of neuroendocrine cells — cells that receive signals from neurons and then release signals, like hormones, to other organs in the body.
The researchers also compared what genes were expressed in cnidarian and comb jelly neurons. They found that as well as having some short neuropeptides in common, both neurons also expressed a similar array of other proteins essential for neuronal function.
“We already know that cnidarian peptide-expressing neurons are homologous to those seen in more complex animals. Now, comb jelly neurons have also been found to have a similar “genetic signature,” suggesting that these neurons share the same evolutionary origin,” said Prof. Watanabe. “In other words, it’s most likely that neurons only evolved once.”
This means, added Prof. Watanabe, that peptide-expressing neurons are probably the most ancestral form, with chemical neurotransmitters arising later. For Prof. Watanabe, these findings bring new, exciting questions to the forefront of his research.
“If this is true, I’m most interested to know — where did the peptide-expressing neurons come from? And why did the ancestral animal need to evolve neurons? Now that we have a clearer idea of what the earliest neurons looked like, research into their original function can begin.”
A randomized single-blind controlled trial of a prototype digital polytherapeutic for tinnitus
by Grant D. Searchfield, Philip J. Sanders in Frontiers in Neurology
After 20 years searching for a cure for tinnitus, researchers at the University of Auckland are excited by ‘encouraging results’ from a clinical trial of a mobile-phone-based therapy. The study randomised 61 patients to one of two treatments, the prototype of the new ‘digital polytherapeutic’ or a popular self-help app producing white noise.
On average, the group with the polytherapeutic (31 people) showed clinically significant improvements at 12 weeks, while the other group (30 people) did not. The results have just been published in Frontiers in Neurology.
“This is more significant than some of our earlier work and is likely to have a direct impact on future treatment of tinnitus,” Associate Professor in Audiology Grant Searchfield says.
Key to the new treatment is an initial assessment by an audiologist who develops the personalised treatment plan, combining a range of digital tools, based on the individual’s experience of tinnitus.
“Earlier trials have found white noise, goal-based counselling, goal-oriented games and other technology-based therapies are effective for some people some of the time,” says Dr Searchfield. “This is quicker and more effective, taking 12 weeks rather than 12 months for more individuals to gain some control.”
There is no pill that can cure tinnitus.
“What this therapy does is essentially rewire the brain in a way that de-emphasises the sound of the tinnitus to a background noise that has no meaning or relevance to the listener,” Dr Searchfield says.
Audiology research fellow Dr Phil Sanders says the results are exciting and he found running the trial personally rewarding.
“Sixty-five percent of participants reported an improvement. For some people, it was life-changing — where tinnitus was taking over their lives and attention.”
Some people didn’t notice an improvement and their feedback will inform further personalisation, Dr Sanders says.
Tinnitus is a phantom noise and its causes are complex. It has so far defied successful treatment.
While most people experience tinnitus, or ringing in the ears at least on occasions, around five percent experience it to a distressing degree. Impacts can include trouble sleeping, difficulty carrying out daily tasks and depression.
Dr Searchfield says seeing his patients’ distress and having no effective treatment to offer inspired his research. “I wanted to make a difference.”
The next step will be to refine the prototype and proceed to larger local and international trials with a view to FDA approval.
The researchers hope the app will be clinically available in around six months.
Transfer from spatial education to verbal reasoning and prediction of transfer from learning-related neural change
by Robert A. Cortes, Emily G. Peterson, David J. M. Kraemer, Robert A. Kolvoord, David H. Uttal, Nhi Dinh, Adam B. Weinberger, Richard J. Daker, Ian M. Lyons, Daniel Goldman, Adam E. Green in Science Advances
The traditional tests and grades that educators have long used may measure learning less accurately than scans of the brain, according to a new study published in Science Advances. The paper, authored by a team of researchers from seven universities and led by Georgetown neuroscientists, could not only upend how educators craft curricula, but reveals a hidden link in the human mind.
“For a long time, psychologists and philosophers have debated whether spatial thinking, like mental images of objects, is actually hiding underneath thinking that seems verbal,” explains Adam Green, the study’s senior author and Provost’s Distinguished Associate Professor at Georgetown College of Arts and Sciences in the Department of Psychology. “If this is true, then teaching students to improve their spatial thinking skills should boost their verbal reasoning ability.”
The researchers studied a “spatially-enriched” science course offered at public high schools in Virginia that emphasizes spatial thinking skills, like building maps and planning how cities can be reconfigured to reduce energy consumption. Magnetic Resonance Imaging (MRI) scans showed changes in students’ brains as they learned the course curriculum, and these changes were compared to the ways that learning is traditionally measured (e.g., changes in test scores).
The brain changes were far better predictors of learning, especially a kind of learning called “far transfer,” which is so deep that it helps students succeed at tasks they weren’t even taught to accomplish. Far transfer is something of a holy grail for educators and notoriously difficult to capture with traditional tests.
The team’s findings support Mental Model Theory, or MMT, which posits that when humans comprehend spoken or written language the mind “spatializes” this information, relying on systems in the brain that originally evolved to help our primate ancestors nimbly navigate complex environments.
When the researchers tested verbal reasoning, about words in sentences rather than objects on maps, they found marked improvements in the students who had taken the course emphasizing spatial thinking. What’s more, the better students got at spatial thinking, the more their verbal reasoning improved.
“These findings demonstrate that mental modeling could be an important basis for far transfer in real-world education, taking skills from the classroom and applying them more generally,” says lead author and Psychology Ph.D. student Robert Cortes (C’18, G’23). “This study not only informs our understanding of how education changes our brains, but it also reveals key insights into the nature of the mind.”
“Verbal reasoning is one of the most powerful tools that human evolution has produced,” Cortes argues. “It is incredibly exciting to combine neuroscience and education to better understand how the human brain learns to reason. Hopefully we can leverage these findings to improve human reasoning more broadly.”
Showing new evidence for MMT in the brain, the research team found that improvements in verbal reasoning could be best predicted by changes in centers of spatial processing in students’ brains — specifically in the posterior parietal cortex.
While the debate about mental models has a long history, one of the hottest debates in the modern educational landscape is whether neuroscience can improve teaching and learning in schools. Though promising in theory, efforts to integrate neuroscience with education have proved challenging in the real world. One of the major obstacles is that neuroscience tools, like MRI scans, are expensive and time-consuming, making it unlikely that they can be applied at a large scale in education policy and practice.
“We can’t scan every kid’s brain, and it would be a really bad idea to do that even if it was possible,” says Green, who is also a faculty member in the Interdisciplinary Program in Neuroscience.
Critics have long expressed concerns about whether the data that neuroscience provides can really tell educators anything they couldn’t find out using traditional paper and pencil or computer-based tests.
The research team’s new findings point to a new way of integrating neuroscience with education that helps to overcome these challenges. Instead of focusing on each individual student’s brain, the study focused on the curriculum the students learned. The results show that brain imaging can detect the changes that come with learning a specific curriculum in real-world classrooms, and that these brain changes can be used to compare different curricula.
“Curriculum development can and does happen at the kinds of small scales that neuroscience can realistically accommodate,” Green says. “So, if we can leverage neuroimaging tools to help identify the ways of teaching that impart the most transferable learning, then those curricula can be widely adopted by teachers and school systems. The curricula can scale up, but the neuroimaging doesn’t have to.”
Students in the spatially-enriched curriculum showed more robust brain changes compared to closely matched students who took other advanced science curricula. These changes appear to indicate a deep learning of spatial abilities that the brain can apply in highly flexible ways, which may not be fully captured by traditional tests of specific skills. In particular, the study’s finding that brain changes can predict learning better than traditional tests provides strong evidence that the inside view afforded by neuroscience can give educators insights about far-transfer learning that they have long sought but that traditional learning assessments often miss.
According to Cortes, “This study is a great example of our department’s mission of bridging ‘Neurons to Neighborhoods’ through science. We hope to use this data to convince policymakers to increase access to this kind of spatially-enriched education.”
EGFR ligand shifts the role of EGFR from oncogene to tumour suppressor in EGFR-amplified glioblastoma by suppressing invasion through BIN3 upregulation
by Gao Guo, Ke Gong, Nicole Beckley, Yue Zhang, Xiaoyao Yang, Rati Chkheidze, Kimmo J. Hatanpaa, Tomas Garzon-Muvdi, Prasad Koduru, Arifa Nayab, Jennifer Jenks, Adwait Amod Sathe, Yan Liu, Chao Xing, Shwu-Yuan Wu, Cheng-Ming Chiang, Bipasha Mukherjee, Sandeep Burma, Bryan Wohlfeld, Toral Patel, Bruce Mickey, Kalil Abdullah, Michael Youssef, Edward Pan, David E. Gerber, Shulan Tian, Jann N. Sarkaria, Samuel K. McBrayer, Dawen Zhao, Amyn A. Habib in Nature Cell Biology
UT Southwestern researchers have identified a molecular pathway responsible for the spread of glioblastoma to surrounding tissue in the brain, as well as an existing drug that curbed tumor growth in animal models. The findings, published in Nature Cell Biology, have led to a clinical trial that could offer new hope to patients with glioblastoma, the most common form of brain cancer in adults that kills hundreds of thousands of people worldwide each year.
“Glioblastoma’s invasive property is perhaps its most formidable barrier to treatment,” said Amyn Habib, M.D., Associate Professor of Neurology, member of both the Harold C. Simmons Comprehensive Cancer Center and Peter O’Donnell Jr. Brain Institute at UTSW, and a staff physician at the Dallas VA Medical Center. “We have identified a pathway that can suppress this cellular invasion, which could offer a new way to increase survival.”
Despite decades of research, the prognosis for most patients with glioblastoma remains dismal, with a median survival after diagnosis of just 15–18 months. Part of the challenge in treating this cancer is its invasive nature: Glioblastoma tumors invade surrounding healthy brain tissue, sending tentacle-like extensions out from the primary tumor that are impossible to remove with surgery alone and difficult to reach with chemotherapy.
Researchers have long considered the epidermal growth factor receptor (EGFR), a protein that sits on the surface of cells, as a driver of this cancer, Dr. Habib explained. In nearly half of glioblastoma patients, the gene that codes for EGFR is amplified, causing glioblastoma cells to produce far more molecular signals spurred by this protein and causing tumor cells to proliferate. Consequently, Dr. Habib added, several clinical trials have focused on inhibiting EGFR — but each has failed to improve the prognosis for glioblastoma.
EGFR on glioblastoma cells can send these signals in two ways: either without prompting, a state known as constitutive signaling, or when stimulated with proteins called ligands. The differences between these two pathways have been considered inconsequential, Dr. Habib said. Thus, glioblastoma patients with amplified EGFR have been grouped together in clinical trials.
In the new study, Dr. Habib and colleagues in the Habib lab and elsewhere showed that when cells with amplified EGFR were stimulated with ligands, this receptor appeared to act as a tumor suppressor, preventing invasion into healthy tissue both in laboratory and animal models. Further experiments showed that a cytoskeletal protein called BIN3 appears to be responsible for inhibiting this invasion. When the researchers dosed animals with amplified EGFR glioblastoma tumors with an FDA-approved arthritis drug called tofacitinib that increases the amount of EGFR ligands and BIN3, tumors remained smaller and were less likely to invade healthy brain tissue. Additionally, these animals survived significantly longer than animals that didn’t receive this drug.
Dr. Habib noted that tofacitinib could offer a new way to extend life for patients with both amplified EGFR and a relatively high level of EGFR ligands, a strategy he and his colleagues will explore in a clinical trial launching in September. For patients without high ligand numbers, he added, strategies previously explored to inhibit EGFR could potentially extend survival.
“These approaches could offer new tools in our arsenal to fight glioblastoma,” Dr. Habib said.
MISC
Subscribe to Paradigm!
Medium, Twitter, Telegram, Telegram Chat, LinkedIn, and Reddit.
Main sources
Research articles
