NS/ Nanoplastics promote conditions for Parkinson’s across various lab models
Neuroscience biweekly vol. 98, 8th November — 22nd November
TL;DR
- Nanoplastics interact with a particular protein that is naturally found in the brain, creating changes linked to Parkinson’s disease and some types of dementia.
- Researchers have identified a protein key to the development of a type of brain cell believed to play a role in disorders like Alzheimer’s and Parkinson’s diseases and used the discovery to grow the neurons from stem cells for the first time. The stem-cell-derived norepinephrine neurons of the type found in a part of the human brain called the locus coeruleus may enable research into many psychiatric and neurodegenerative diseases and provide a tool for developing new ways to treat them.
- The boiling frog parable seems to have inspired new research, which identified a brain pathway responsible for rapid threat detection.
- Researchers have shed new light on why electroconvulsive therapy has such a high success rate, a mystery that has puzzled doctors and scientists for almost a century. Findings could help improve this controversial treatment.
- A hunger hormone produced in the gut can directly impact a decision-making part of the brain in order to drive an animal’s behavior, finds a new study.
- Doctors often prescribe radiation along with surgery to treat a brain tumor called meningioma that originates in the protective membranes surrounding the brain. But side effects from radiation can be serious, including memory loss and cognitive decline, so it’s important to know which patients really need it. Now, researchers at UC San Francisco and Northwestern Medicine, in collaboration with 10 other medical centers, have found a highly accurate way to predict the best treatment for patients based on patterns of gene expression — which genes are turned on and off — in their tumors.
- Researchers have shown how the tau protein, known for its role in dementias, behaves where communication in the brain takes place.
- The discovery of the phantom touch illusion provides insights into human perception and opens up new perspectives for interaction with virtual reality technology.
- When we engage in social interactions, like shaking hands or having a conversation, our observation of other people’s actions is crucial. But what exactly happens in our brain during this process: how do the different brain regions talk to each other? Researchers provide an intriguing answer: our perception of what others do depends more on what we expect to happen than previously believed.
- A new large-scale longitudinal study carried out by University of Sussex psychologists has found a clear link between episodes of depression and anxiety experienced by adults in their twenties, thirties and forties, with a decrease in memory function by the time they are in their fifties.
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.
The latest news and research
Anionic nanoplastic contaminants promote Parkinson’s disease–associated α-synuclein aggregation
by Zhiyong Liu, Arpine Sokratian, Addison M. Duda, Enquan Xu, Christina Stanhope, Amber Fu, Samuel Strader, Huizhong Li, Yuan Yuan, Benjamin G. Bobay, Joana Sipe, Ketty Bai, Iben Lundgaard, Na Liu, Belinda Hernandez, Catherine Bowes Rickman, Sara E. Miller, Andrew B. West in Science Advances
Nanoplastics interact with a particular protein that is naturally found in the brain, creating changes linked to Parkinson’s disease and some types of dementia.
In a Duke-led study appearing in Science Advances, the researchers report that the findings create a foundation for a new area of investigation, fueled by the timely impact of environmental factors on human biology.
“Parkinson’s disease has been called the fastest growing neurological disorder in the world,” said principal investigator, Andrew West, Ph.D., professor in the Department of Pharmacology and Cancer Biology at Duke University School of Medicine. “Numerous lines of data suggest environmental factors might play a prominent role in Parkinson’s disease, but such factors have for the most part not been identified.”
Improperly disposed plastics have been shown to break into very small pieces and accumulate in water and food supplies, and were found in the blood of most adults in a recent study.
“Our study suggests that the emergence of micro and nanoplastics in the environment might represent a new toxin challenge with respect to Parkinson’s disease risk and progression,” West said. “This is especially concerning given the predicted increase in concentrations of these contaminants in our water and food supplies.”
West and colleagues in Duke’s Nicholas School of the Environment and the Department of Chemistry at Trinity College of Arts and Sciences found that nanoparticles of the plastic polystyrene — typically found in single use items such as disposable drinking cups and cutlery — attract the accumulation of the protein known as alpha-synuclein. West said the study’s most surprising findings are the tight bonds formed between the plastic and the protein within the area of the neuron where these accumulations are congregating, the lysosome.
Researchers said the plastic-protein accumulations happened across three different models performed in the study — in test tubes, cultured neurons, and mouse models of Parkinson’s disease. West said questions remain about how such interactions might be happening within humans and whether the type of plastic might play a role.
“While microplastic and nanoplastic contaminants are being closely evaluated for their potential impact in cancer and autoimmune diseases, the striking nature of the interactions we could observe in our models suggest a need for evaluating increasing nanoplastic contaminants on Parkinson’s disease and dementia risk and progression,” West said.
“The technology needed to monitor nanoplastics is still at the earliest possible stages and not ready yet to answer all the questions we have,” he said. “But hopefully efforts in this area will increase rapidly, as we see what these particles can do in our models. If we know what to look out for, we can take the necessary steps to protect ourselves, without compromising all the benefits we reap every day from plastics.”
Generation of locus coeruleus norepinephrine neurons from human pluripotent stem cells
by Yunlong Tao, Xueyan Li, Qiping Dong, Linghai Kong, Andrew J. Petersen, Yuanwei Yan, Ke Xu, Seth Zima, Yanru Li, Danielle K. Schmidt, Melvin Ayala, Sakthikumar Mathivanan, Andre M. M. Sousa, Qiang Chang, Su-Chun Zhang in Nature Biotechnology
Researchers at the University of Wisconsin-Madison have identified a protein key to the development of a type of brain cell believed to play a role in disorders like Alzheimer’s and Parkinson’s diseases and used the discovery to grow the neurons from stem cells for the first time.
The stem-cell-derived norepinephrine neurons of the type found in a part of the human brain called the locus coeruleus may enable research into many psychiatric and neurodegenerative diseases and provide a tool for developing new ways to treat them.
Yunlong Tao, an investigator at Nanjing University in China who was a research professor at UW-Madison’s Waisman Center when the study was performed, and Su-Chun Zhang, a UW-Madison professor of neuroscience and neurology, published their work on the cells, which they call LC-NE neurons, in the journal Nature Biotechnology.
Norepinephrine neurons in the locus coeruleus regulate heartbeat, blood pressure, arousal, memory, attention and “fight or flight” reactions. Humans have approximately 50,000 LC-NE neurons in the hindbrain, where the locus coeruleus is. From there, the LC-NE neurons reach into all parts of the brain and the spinal cord.
“The norepinephrine neurons in the locus coeruleus are essential for our life. We call it the life center,” Zhang says. “Without these nerve cells, we would probably be extinct from Earth.”
These neurons also play a role, albeit unknown, in various neurodegenerative and neuropsychiatric diseases. In many neurodegenerative diseases such as Alzheimer’s and Parkinson’s, the neurons start degenerating at a very early stage — sometimes years before other brain regions begin to falter.
“People have noticed this for a long time, but they don’t know what the function of the locus coeruleus is in this process. And partly because we don’t have a good model to mimic the human LC-NE neurons,” says Tao, first author of the study.
Previous attempts at creating these neurons from human stem cells followed a protocol based on the development of LC-NE neurons in mouse models. For two years, Tao explored why these attempts were failing and how development of the neurons from stem cells was different in humans.
In the new study, he identified ACTIVIN-A, a protein that belongs to a family of growth factors, as important in regulating neurogenesis in human NE neurons.
“We have some new understanding about locus coeruleus development,” Tao says. “That’s the major finding in this paper, and based on that finding, we are able to generate locus coeruleus norepinephrine neurons.”
To create LC-NE neurons, the researchers converted human pluripotent stem cells into cells from the hindbrain. Then, using ACTIVIN-A and a series of additional signals, they steered cell development toward their fate as LC-NE neurons.
Once converted, the cells showed typical characteristics of functioning LC-NE neurons in the human brain, releasing the neurotransmitter norepinephrine. They also showed axonal arborization — extension of the long, branching arms of neurons that enable the connections between brain cells — and reacted to the presence of carbon dioxide, which is crucial for breathing control.
The new cells may serve as models for disease in humans, allowing scientists to screen drugs for potential treatments and answer questions such as why the cells in the locus coeruleus die so early in neurodegenerative diseases.
“If this is somewhat causative, then we could potentially do something to prevent or delay the neurodegeneration process,” Zhang says.
The LC-NE cells may someday serve as stem-cell therapy themselves.
“The application of these cells is quite broad in its significance,” Zhang says.
Next, the researchers plan to examine the detailed mechanisms through which ACTIVIN-A regulates LC-NE neuron development. The group will also use the cells for the translational work of drug screening and disease modeling.
Rapid threat assessment in the Drosophila thermosensory system
by Genevieve C. Jouandet, Michael H. Alpert, José Miguel Simões, Richard Suhendra, Dominic D. Frank, Joshua I. Levy, Alessia Para, William L. Kath, Marco Gallio in Nature Communications
We’ve all heard it: Put a frog in boiling water, and it will jump out. But put the same frog in lukewarm water and heat it gradually, and you’ll cook the frog. Often used as a metaphor for the unhurried and stubborn response many have to a slowly rising threat, the mechanisms underlying the urban myth have become a subject of scientific fascination.
This parable seems to have inspired new Northwestern University research, which identified a brain pathway responsible for rapid-threat detection.
“Animals are more likely to react to rapid rather than slow environmental change,” said lead author Marco Gallio, associate professor of neurobiology in Northwestern’s Weinberg College of Arts and Sciences. “In the present study, we identify a brain circuit in fruit flies that selectively responds to rapid thermal change, priming behavior for escape.”
Gallio generally uses fruit flies to understand sensory circuits and the ways they create perceptions of the physical world. Using the fly as a model, the lab studies basic decision-making principles in an animal that has a fraction of the number of neurons (100,000) than humans have (roughly 100 billion). As a well-studied model organism for biological research, flies also are useful subjects because of the pre-existing tools to study fly neurons and behavior.
“There are often two types of responses to external stimuli in the brain: Some neurons respond to a stimulus like light or temperature with very persistent activity,” Gallio said. “Other neurons fire just at the beginning, like when a light turns on, and then their activity is gone. We’ve always wondered what the significance of these short-lived responses is.”
In visual stimuli, brains are wired to notice a large contrast between light and dark. Gallio said that the response intuitively also makes sense for the sense of touch: You don’t think about pressure when your hand is resting on a surface. Run your hand over something new, however, and you will detect subtle changes in texture. Gallio’s team wanted to see if the same was true for the sense of temperature.
To explore how flies respond to rapid change, the team used a high-resolution camera to observe flies navigating different temperature environments. When flies encounter a rapid heat front, they always produce a U-turn away from it.
The lab found flies always responded in cases of rapid temperature change, but not for slow change.
The team also identified a circuit in the fly brain that responds only to rapid temperature change (more than 0.2 degrees Celsius per second). Much like light-ON cells of the visual system, these neurons fired at the beginning of rapid heating and then went quiet.
“Our hypothesis was that these heat-ON responses may indeed correlate with the rate of temperature change,” said Jenna Jouandet, the study’s first author and a Ph.D. student in the Gallio Lab. “And therefore, may allow flies to anticipate dangerous thermal conditions and prepare to escape.”
Indeed, when the researchers experimentally inactivated those neurons, flies escaped less promptly.
To better understand how the activity of these neurons may be important for the behavior of the fly, the researchers collaborated with William Kath, applied math professor at Northwestern and deputy director of the new National Institute for Theory and Mathematics in Biology. Applied math Ph.D. student Richard Suhendra built a small computer model with two antennae and two wheels to demonstrate how adding a neuron that anticipates dangerous heat could improve the flexibility of the vehicle response. (Play with the model through a simple game on the Gallio Lab webpage.)
“The neurons that we initially discovered take input from the thermosensory neurons on the antennae and carry information to the higher brain,” Gallio said. “Flies are a great model to map brain circuits in that we were able to reconstruct the full circuit from sensory neurons all the way down to the centers that produce movement.”
Gallio explained that rapid changes are nearly always dangerous for a small fly.
“If the temperature is changing by half a degree per second — which is not that much — within 30 or 40 seconds, that fly could be dead,” Gallio said. “This system is an alarm bell that rings to prime an animal’s behavior for escape. We see the fly escape.”
Gallio hypothesizes that the results are broadly generalizable, especially because he sees it play out in humans, whether someone is entering a room that’s a different temperature or getting into a hot shower. He said these neurons seem to be able to sense something others do not — they seem to be able to anticipate the future.
Magnetic seizure therapy and electroconvulsive therapy increase aperiodic activity
by Sydney E. Smith, Eena L. Kosik, Quirine van Engen, Jordan Kohn, Aron T. Hill, Reza Zomorrodi, Daniel M. Blumberger, Zafiris J. Daskalakis, Itay Hadas, Bradley Voytek in Translational Psychiatry
&
Clinical EEG slowing induced by electroconvulsive therapy is better described by increased frontal aperiodic activity
by Sydney E. Smith, Vincent Ma, Celene Gonzalez, Angela Chapman, David Printz, Bradley Voytek, Maryam Soltani in Translational Psychiatry
Electroconvulsive therapy (ECT), formerly known as electroshock therapy, involves inducing a brief seizure in the brain using controlled doses of electricity. While ECT is highly effective for certain mental illnesses, particularly depression, the reasons for its efficacy have long puzzled the fields of psychiatry and neuroscience.
Now, researchers from the University of California San Diego may have an answer. In two new studies published in Translational Psychiatry, they propose a new hypothesis that ECT alleviates depression symptoms by increasing aperiodic activity, a type of electrical activity in the brain that doesn’t follow a consistent pattern and is generally considered to be the brain’s background noise.
“We’re solving a puzzle that’s stumped scientists and doctors since electroconvulsive therapy was first developed nearly a century ago,” said first author Sydney Smith, a PhD candidate in the Voytek Lab at UC San Diego. “On top of that, we’re also helping to demystify one of the most effective, yet stigmatized treatments for severe depression.”
Electroconvulsive therapy has a great track record, but a bad reputation. The therapy is effective in up to 80% of patients who receive the treatment, most often for depression but occasionally for bipolar disorder or schizophrenia. However, despite this high success rate, electroconvulsive therapy is frequently associated with frightening images of people receiving painful, high voltage shocks.
“A lot of people are surprised to learn that we still use electroconvulsive therapy, but the modern procedure uses highly controlled dosages of electricity and is done under anesthesia,” said Smith. “It really doesn’t look like what you see in movies or television.”
While generally safe and effective, ECT does have drawbacks, including temporary confusion and cognitive impairment. It also requires multiple outpatient visits, which can present a barrier to some people who might otherwise benefit from the treatment.
“One of the reasons ECT isn’t more popular is that for a lot of people, it’s easier and more convenient to just take a pill,” said senior author Bradley Voytek, PhD, professor of cognitive science at UC San Diego. “However, in people for whom medications don’t work, electroconvulsive therapy can be life-saving. Understanding how it works will help us discover ways to increase the benefits while minimizing side effects.”
The researchers used electroencephalography (EEG) scans to study the brain activity of patients who received ECT therapy for depression. They also looked at another similar form of treatment called magnetic seizure therapy, which induces a seizure with magnets instead of electrodes. Both therapies showed increased aperiodic activity levels in patients’ brains post-treatment.
“Aperiodic activity is like the brain’s background noise, and for years scientists treated it that way and didn’t pay much attention to it,” said Smith. “However, we’re now seeing that this activity actually has an important role in the brain, and we think electroconvulsive therapy helps restore this function in people with depression.”
One of the functions of aperiodic activity in the brain is helping control how neurons turn on and off. Our neurons are constantly going through cycles of excitation and inhibition that correspond with different mental states. Aperiodic activity helps boost inhibitory activity in the brain, effectively slowing it down.
“Something we see regularly in the EEG scans of people who receive electroconvulsive or magnetic seizure therapy is a slowing pattern in the brain’s electrical activity,” said Smith. “This pattern has gone unexplained for many years, but accounting for the inhibitory effects of aperiodic activity helps explain it. It also suggests that these two forms of therapy are causing similar effects in the brain.”
While these findings establish a link between aperiodic activity and ECT benefits, the researchers stress the need for further investigation to leverage these insights in clinical applications. They are currently exploring the possibility of using aperiodic activity as a metric of treatment effectiveness in other depression treatments, such as medications.
“At the end of the day, what’s most important to patients and to doctors is that the treatment works, which in the case of ECT, it does,” said Voytek. “However, it’s our job as scientists to dig into what’s really going on in the brain during these treatments, and continuing to answer those questions will help us find ways to make these treatments even more effective while reducing negative effects.”
Internal-state-dependent control of feeding behavior via hippocampal ghrelin signaling
by Ryan W.S. Wee, Karyna Mishchanchuk, Rawan AlSubaie, Timothy W. Church, Matthew G. Gold, Andrew F. MacAskill in Neuron
A hunger hormone produced in the gut can directly impact a decision-making part of the brain in order to drive an animal’s behaviour, finds a new study by UCL (University College London) researchers.
The study in mice, published in Neuron, is the first to show how hunger hormones can directly impact activity of the brain’s hippocampus when an animal is considering food.
Lead author Dr Andrew MacAskill (UCL Neuroscience, Physiology & Pharmacology) said:
“We all know our decisions can be deeply influenced by our hunger, as food has a different meaning depending on whether we are hungry or full. Just think of how much you might buy when grocery shopping on an empty stomach. But what may seem like a simple concept is actually very complicated in reality; it requires the ability to use what’s called ‘contextual learning’.
“We found that a part of the brain that is crucial for decision-making is surprisingly sensitive to the levels of hunger hormones produced in our gut, which we believe is helping our brains to contextualise our eating choices.”
For the study, the researchers put mice in an arena that had some food, and looked at how the mice acted when they were hungry or full, while imaging their brains in real time to investigate neural activity. All of the mice spent time investigating the food, but only the hungry animals would then begin eating.
The researchers were focusing on brain activity in the ventral hippocampus (the underside of the hippocampus), a decision-making part of the brain which is understood to help us form and use memories to guide our behaviour.
The scientists found that activity in a subset of brain cells in the ventral hippocampus increased when animals approached food, and this activity inhibited the animal from eating.
But if the mouse was hungry, there was less neural activity in this area, so the hippocampus no longer stopped the animal from eating. The researchers found this corresponded to high levels of the hunger hormone ghrelin circulating in the blood.
Adding further clarity, the UCL researchers were able to experimentally make mice behave as if they were full, by activating these ventral hippocampal neurons, leading animals to stop eating even if they were hungry. The scientists achieved this result again by removing the receptors for the hunger hormone ghrelin from these neurons.
Prior studies have shown that the hippocampus of animals, including non-human primates, has receptors for ghrelin, but there was scant evidence for how these receptors work.
This finding has demonstrated how ghrelin receptors in the brain are put to use, showing the hunger hormone can cross the blood-brain barrier (which strictly restricts many substances in the blood from reaching the brain) and directly impact the brain to drive activity, controlling a circuit in the brain that is likely to be the same or similar in humans.
Dr MacAskill added:
“It appears that the hippocampus puts the brakes on an animal’s instinct to eat when it encounters food, to ensure that the animal does not overeat — but if the animal is indeed hungry, hormones will direct the brain to switch off the brakes, so the animal goes ahead and begins eating.”
The scientists are continuing their research by investigating whether hunger can impact learning or memory, by seeing if mice perform non-food-specific tasks differently depending on how hungry they are. They say additional research might also shed light on whether there are similar mechanisms at play for stress or thirst.
The researchers hope their findings could contribute to research into the mechanisms of eating disorders, to see if ghrelin receptors in the hippocampus might be implicated, as well as with other links between diet and other health outcomes such as risk of mental illnesses.
Targeted gene expression profiling predicts meningioma outcomes and radiotherapy responses
by Stephanie L. Pugh, Minesh P. Mehta, Penny K. Sneed, Mitchel S. Berger, Craig M. Horbinski, Michael W. McDermott, Arie Perry, Wenya Linda Bi, Akash J. Patel, Felix Sahm, Stephen T. Magill, David R. Raleigh in Nature Medicine
Doctors often prescribe radiation along with surgery to treat a brain tumor called meningioma that originates in the protective membranes surrounding the brain. But side effects from radiation can be serious, including memory loss and cognitive decline, so it’s important to know which patients really need it.
Now, researchers at UC San Francisco and Northwestern Medicine, in collaboration with 10 other medical centers, have found a highly accurate way to predict the best treatment for patients based on patterns of gene expression — which genes are turned on and off — in their tumors.
Screening tumors using this new approach could change the course of treatment for nearly 1 in 3 people with meningioma, the most common form of brain tumor diagnosed in 42,000 Americans each year. Unlike other brain tumors, meningiomas occur most often in female, Black and elderly patients.
In a paper appearing in Nature Medicine, the team concluded that just 1 in 5 patients with low-grade tumors (those less likely to regrow) may need radiation, while around 2 in 5 with higher-grade tumors may be better off without radiation, based on the results of the new gene-expression test.
“There’s been a lot of controversy in the field in terms of who should receive radiotherapy and who shouldn’t,” said David Raleigh, MD, PhD, a radiation oncologist in the UCSF Brain Tumor Center and a senior author of the study, along with Stephen Magill, MD, PhD, assistant professor of neurological surgery at Northwestern University Feinberg School of Medicine. “Our biomarker takes the guessing game out of this and shows us which patients are likely to benefit from radiotherapy and which may get toxicity and possibly no benefit from radiation.”
Because meningiomas grow slowly, a patient may be unaware of their tumor until they start to experience neurological symptoms like numbness, vision loss or personality changes. There are no pharmaceutical treatments, so doctors rely on surgery to remove the tumor and radiation to prevent it from growing back. Doctors treat these tumors based on guidance from the World Health Organization, which stages them according to severity.
Pathologists currently classify meningiomas by looking at them under a microscope for features that indicate whether they may grow back, a system that is very good but not perfect. Patients with Grade 1 tumors don’t usually receive radiation treatment if their tumors can be removed completely during surgery. Yet approximately 20% of the time, the tumors recur. Those with Grade 2 and 3 tumors, which are much more aggressive and more likely to grow back after surgery, are often treated with radiation after surgery. It has been unclear how many of these patients, particularly those with Grade 2 tumors, actually need radiation treatment.
Raleigh, along with Magill and lead author William Chen, MD, decided to look at classifying tumors according to which of their genes are turned on and off, thereby offering clues to how aggressive they might be.
“Gene-expression tests like this, that analyze a small number of genes at a time, are widely available for breast, prostate and some other cancers, and they’ve proven to be a very accurate and inexpensive alternative to other types of tests,” said Chen.
Raleigh and Chen and their multidisciplinary team suspected that gene expression could more accurately point out the patients who would be helped by radiotherapy. Using samples from 1,856 meningioma patients at 12 medical centers in the U.S., Europe and Hong Kong, Raleigh’s team came up with a set of 34 genes whose gene expression patterns had the potential to predict whether a tumor would return.
One-fifth of the Grade 1 tumors — the same number that grow back after surgery — expressed the patterns that Raleigh’s team found could predict a tumor’s regrowth. This fraction of patients may benefit from radiation. The researchers also found that two-fifths of patients with Grade 2 and 3 tumors did not have a recurrence, and this, too, could be predicted by the tumor’s gene expression.
“When to proceed with additional surgery, radiotherapy or simply to observe a small residual meningioma is not always clear,” said Magill. “This test adds information that can let us tailor our surgical and radiation approach to provide the best outcome for each patient and maximize both quality and quantity of life.”
The team’s next step is to test the approach in two clinical trials currently being developed.
Tau forms synaptic nano-biomolecular condensates controlling the dynamic clustering of recycling synaptic vesicles
by Shanley F. Longfield, Mahdie Mollazade, Tristan P. Wallis, Rachel S. Gormal, Merja Joensuu, Jesse R. Wark, Ashley J. van Waardenberg, Christopher Small, Mark E. Graham, Frédéric A. Meunier, Ramón Martínez-Mármol in Nature Communications
For the first time, University of Queensland (UQ) researchers have shown how the tau protein, known for its role in dementias, behaves where communication in the brain takes place.
The study led by Dr Ramón Martínez-Mármol and PhD student Shanley Longfield from UQ’s Queensland Brain Institute used super-resolution microscopy to visualise individual tau proteins in motion while neurons are “talking” to each other.
Dr Martínez-Mármol explained that the team’s discovery is a big step towards understanding what triggers tau aggregation in disease states like Alzheimer’s disease.
“We discovered that tau in a healthy brain controls an important population of vesicles at the presynapse critical for neuronal communication,” Dr Martínez-Mármol said. “These vesicles are like the words that neurons use to transmit information to other neurons. For the very first time, we’ve shed light on the mechanism by which tau acts in our nerve cells. By understanding tau’s role in a healthy context, we begin to fully understand what leads to the abnormal accumulation of tau in disease.”
Ms Longfield said that observing tau’s behaviour in healthy states provides clues to how these toxic aggregates start to form.
“Studying tau in a healthy brain is more challenging than studying it in a diseased brain, where changes in its molecular behaviour are far more prominent and obvious,” Ms Longfield said. “But by visualising tau at the nanoscale and in this context, we can identify the molecular behaviours that precede the formation of toxic protein aggregates in disease.”
The team also discovered that tau molecules form tiny condensates, dense gel-like bodies within brain cells, which resemble oil droplets suspended in water.
“What we noticed is that these tau condensates are very fluid-like and dynamic and are tightly regulated by synaptic activity,” Ms Longfield said. “In neurodegenerative disorders, these condensates get bigger and denser and eventually form aggregates, which are destructive to brain function. Our next challenge is to track diseased tau in brain cells to see how this new function is altered, leading to tau aggregation.”
Phantom touch illusion, an unexpected phenomenological effect of tactile gating in the absence of tactile stimulation
by Artur Pilacinski, Marita Metzler, Christian Klaes in Scientific Reports
Virtual reality (VR) is not only a technology for games and entertainment, but also has potential in science and medicine. Researchers at Ruhr University Bochum, Germany, have now gained new insights into human perception with the help of VR. They used virtual reality scenarios in which subjects touched their own bodies with a virtual object. To the researchers’ surprise, this led to a tingling sensation at the spot where the avatarized body was touched. This effect occurred even though there was no real physical contact between the virtual object and the body.
“People in virtual reality sometimes have the feeling that they are touching things, although they are actually only encountering virtual objects,” says first author Artur Pilacinski from the Knappschaftskrankenhaus Bochum Langendreer, University Clinic of Ruhr University Bochum, explaining the origin of the research question. “We show that the phantom touch illusion is described by most subjects as a tingling or prickling, electrifying sensation or as if the wind was passing through their hand.”
The neuroscientists wanted to understand what is behind this phenomenon and find out which processes in the brain and body play a role in it. They observed that the phantom touch illusion also occurred when the subjects touched parts of their bodies that were not visible in virtual reality.
Second author Marita Metzler adds:
“This suggests that human perception and body sensation are not only based on vision, but on a complex combination of many sensory perceptions and the internal representation of our body.”
This study involved 36 volunteers wearing VR glasses. First, they got used to the VR environment by moving around and touching virtual objects. Then they were given the task of touching their hand in the virtual environment with a virtual stick.
Participants were asked if they felt anything. If not, they were allowed to continue touching and the question was asked again later. If they felt sensations, they were asked to describe them and rate their intensity on different hand locations. This process was repeated for both hands. There was a consistent reporting of the sensation as “tingling” by a majority of participants.
In a control experiment, it was investigated whether similar sensations could also be perceived without visual contact with virtual objects purely due to experimental situation demands. Here, a small laser pointer was used instead of virtual objects to touch the hand. This control experiment did not result in phantom touch suggesting that phantom touch illusion was unique to virtual touch.
The discovery of the phantom touch illusion opens up new possibilities for further research into human perception and could also be applied in the fields of virtual reality and medicine.
Christian Klaes, member of the Research Department of Neuroscience at Ruhr University, says: “It could even help to deepen the understanding of neurological diseases and disorders that affect the perception of one’s own body.”
The Bochum team plans to continue their research on the phantom touch illusion and the underlying processes. For this reason, a collaboration with the University of Sussex has been started.
“It is important to first distinguish between the actual sensations of phantom touch and other cognitive processes that may be involved in reporting such embodied sensations, such as suggestion, or experimental situation demands,” says Artur Pilacinski. “We also want to further explore and understand the neural basis of the phantom touch illusion in collaboration with other partners.”
Predictability alters information flow during action observation in human electrocorticographic activity
by Chaoyi Qin, Frederic Michon, Yoshiyuki Onuki, Yohei Ishishita, Keisuke Otani, Kensuke Kawai, Pascal Fries, Valeria Gazzola, Christian Keysers in Cell Reports
When we engage in social interactions, like shaking hands or having a conversation, our observation of other people’s actions is crucial. But what exactly happens in our brain during this process: how do the different brain regions talk to each other? Researchers at the Netherlands Institute for Neuroscience provide an intriguing answer: our perception of what others do depends more on what we expect to happen than previously believed.
For some time, researchers have been trying to understand how our brains process other people’s actions. It is known, for example, that watching someone perform an action activates similar brain areas compared to when we perform that action ourselves. People assumed these brain regions become activated in a particular order: seeing what others do first activates visual brain regions, then later, parietal and premotor regions we normally use to perform similar actions. Scientists thought that this flow of information, from our eyes to our own actions, is what makes us understand what others do. This belief is based on measurements of brain activity in humans and monkeys while they watched simple actions, such as picking up a knife, presented in isolation in the lab. In reality, actions don’t usually happen in isolation, out of the blue: they follow a predictable sequence with an end-goal in mind, like making breakfast. How does our brain deal with this?
Chaoyi Qin, Frederic Michon and their colleagues, led by Christian Keysers and Valeria Gazzola provide us with an intriguing answer: if we observe actions in such meaningful sequences, our brains increasingly ignore what comes into our eyes, and depend more on predictions of what should happen next, derived from our own motor system.
“What we would do next, becomes what our brain sees,” summarizes Christian Keysers, a senior author of the study and director of the social brain lab in the institute.
To arrive at that counterintuitive conclusion, the team, in collaboration with the Jichi Medical University in Japan, had the unique opportunity to measure brain activity directly from the brain of epilepsy patients who participated in intracranial eeg-research for medical purposes. Such an examination involves measuring the brain’s electrical activity using electrodes that are not on the skull, but under it.
The advantage of this technique is that it is the only technique that allows to directly measure the electrical activity the brain uses to work. Clinically, it is used as a final step for medication-resistant epilepsy patients, as it can determine the exact source of epilepsy. But while the medical team waits for epileptic seizures to occur, these patients have a period in which they have to stay in their hospital bed and have nothing to do but wait — researchers used this period as an opportunity to peak into the working of the brain with unprecedented temporal and spatial accuracy.
During the experiment, participants performed a simple task: they watched a video in which someone performed various daily actions, such as preparing breakfast or folding a shirt. During that time, their electrical brain activity could be measures through the implanted electrodes across the brain regions involved in action observation to examine how they talk to each other. Two different conditions were tested, resulting in differing brain activity while watching. In one, the video was shown — as we would normally see the action unfold every morning — in its natural sequence: you see someone pick a bread-roll, then a knife, then cut open the roll, then scoop some butter etc.; in the other, these individual acts were re-shuffled into a random order. People saw the exact same actions in the two conditions, but only in the natural order, can their brain utilize its knowledge of how it would butter a bread-roll to predict what action comes next.
Using sophisticated analyses in collaboration with Pascal Fries of the Ernst Strüngmann Institute (ESI) in Germany, what the team could reveal is that when participants viewed the reshuffled, unpredictable sequence, the brain indeed had an information flow going from visual brain regions, thought to describe what the eye is seeing, to parietal and premotor regions, that also controls our own actions — just as the classical model predicted. But when participants could view the natural sequences, the activity changed dramatically.
“Now, information was actually flowing from the premotor regions, that know how we prepare breakfast ourselves, down to the parietal cortex, and suppressed activity in the visual cortex,” explains Valeria Gazzola. “It is as if they stopped to see with their eyes, and started to see what they would have done themselves.”
Their finding is part of wider realization in the neuroscience community, that our brain does not simply react to what comes in through our senses. Instead, we have a predictive brain, that permanently predicts what comes next. The expected sensory input is then suppressed. We see the world from the inside out, rather than from the outside in. Of course, if what we see violates our expectations, the expectation-driven suppression fails, and we become aware of what we actually see rather than what we expected to see.
Longitudinal associations of affective symptoms with mid-life cognitive function: evidence from a British birth cohort
by John, A., James, S.-N., Patel, U., Rusted, J., Richards, M., & Gaysina, D.
A new large-scale longitudinal study carried out by University of Sussex psychologists has found a clear link between episodes of depression and anxiety experienced by adults in their twenties, thirties and forties, with a decrease in memory function by the time they are in their fifties.
The study, published in the British Journal of Psychiatry, is the first of its kind to look at the relationship between depressive symptoms experienced across three decades of early-mid adulthood and a decline in cognitive function in midlife.
The Sussex psychologists analysed data from the National Child Development Study, which was established in 1958 with a cohort of over 18,000 babies and followed participants from birth into childhood and through to adulthood. The Sussex psychologists found that an accumulation of symptoms experienced by participants over the three decades provided a strong indicator of a linear decrease in memory function by the time the adults were fifty.
They found that one episode of depression or anxiety had little effect on the memory function of adults in midlife, regardless of which decade it was experienced, but that once the episodes increased to two or three over the course of the three decades, that this predicted a steady decrease in the participant’s memory function by the time they reached fifty.
This, the psychologists from the EDGE Lab at the University of Sussex argue, highlights an opportunity to protect future memory function by promoting mental health interventions amongst young adults and they are calling on the UK government to invest in the mental health of young adults as a preventative measure to protect the future brain health of our ageing population.
Dr Darya Gaysina, Senior Lecturer in Psychology at the University of Sussex, said: “We found that the more episodes of depression people experience in their adulthood, the higher risk of cognitive impairment they have later in life. This finding highlights the importance of effective management of depression to prevent the development of recurrent mental health problems with long-term negative outcomes.
“We’d therefore like to see the government investing more in the mental health provision for young adults, not only for the immediate benefit of the patients, but also to help protect their future brain health.”
As well as memory, the psychologists also assessed verbal fluency, information processing speed and accuracy scores of the participants once they turned fifty. Encouragingly, episodes of depression and anxiety had little impact on the latter four areas of cognitive function but the associated loss of memory suggests that depressive symptoms experienced in early adulthood could predict dementia in older adulthood.
Previous research carried out by the EDGE Lab at the University of Sussex had found a relationship between depressive symptoms experienced in older adulthood and a faster rate of cognitive decline, but this is the first time that such a large and UK nationally representative sample has been able to make this link in the first three decade of adulthood.
University of Sussex Psychology PhD student Amber John said:
“We knew from previous research that depressive symptoms experienced in mid adulthood to late adulthood can predict a decline in brain function in later life but we were surprised to see just how clearly persistent depressive symptoms across three decades of adulthood are an important predictor of poorer memory function in mid-life.
“With the publication of this research, we’re calling for the government to invest in mental health provision to help stem the risk of repeated episodes of depression and anxiety.
“From an individual’s perspective, this research should be a wake-up call to do what you can to protect your mental health, such as maintaining strong relationships with friends and family, taking up physical exercise or practising mindfulness meditation — all of which have been shown to boost mental health. Then of course, seeing your GP for advice if you feel you need help with depression or anxiety.”
MISC
Subscribe to Paradigm!
Medium, Twitter, Telegram, Telegram Chat, LinkedIn, and Reddit.
Main sources
Research articles
