Lab-grown brain organoids mature like real infant brains
After 20 months, scientists find lab-dish brain cells matured at a similar rate to those of an actual infant.
24 February, 2021
Credit: Girl with the red hat/Unsplash/jolygon/Adobe Stock/Big Think
- Scientists have found that cultures of embryonic brain cells mature at the same rate as a 20-month-old infant's.
- Researchers have looked to such cell structures, called "organoids," as potential models for understanding the human body's biological mechanisms.
- Their study validates the use of lab-dish organoids for research.
<p>Scientists have been growing cell cultures that resemble natural human cells in dishes for a while now, but their usefulness for research has been inhibited by concerns that they never mature enough to provide insights into human development beyond the womb. Now, scientists from UCLA and Stanford have genetically analyzed dish-grown brain organoids that matured over 20 months pretty close to the same timetable that an infant's brain cells would.</p><p>"This will be an important boost for the field. We've shown that these organoids can mature and replicate many aspects of normal human development — making them a good model for studying human disease in a dish," <a href="https://stemcell.ucla.edu/news/brain-organoids-grown-lab-mature-much-infant-brains" target="_blank">says</a> senior author <a href="https://geschwindlab.dgsom.ucla.edu/pages/" target="_blank" rel="noopener noreferrer">Daniel Geschwind</a> of UCLA.</p><p>The research is published in a study in the journal <a href="https://www.nature.com/articles/s41593-021-00802-y" target="_blank">Nature Neuroscience</a>.</p>
What organoids really are and aren't
<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yNTY4MzgzOC9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTY1OTEzMjc5Mn0.R1KWf66xU7CYlT3CPthA2J-xJKjZP0h0W4vx2Quxiq8/img.jpg?width=980" id="60c18" class="rm-shortcode" data-rm-shortcode-id="a496d5eb7684457c09d0139882876a8f" data-rm-shortcode-name="rebelmouse-image" data-width="1440" data-height="1080" />A brain organoid
Credit: NIH Image Gallery/Wikimedia
<p>Organoids are tissue cultures comprised of human embryonic stem cells. They start off as induced pluripotent stem cells (IPS) drawn from skin cells or blood cells before being reprogrammed to revert to an embryonic stem-cell-like state. From there, they can be exposed to chemicals that cause them to behave like a specific type of human cell.</p><p>In the case of this study, the chemicals caused them to become cerebral organoids, self-organized 3D cell structures that behave similarly to natural human brain cells. They don't grow to become full mini-brains.</p>The promise of organoids
<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yNTY4Mzg0MC9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYzMDEzODg0Nn0.AmSwbhi7wxpv1vKOX4jqOhB-pEqJNyFQzu2mhzHWTvc/img.jpg?width=980" id="92a7b" class="rm-shortcode" data-rm-shortcode-id="3746da47064a9d07ca33ddf44c5c1880" data-rm-shortcode-name="rebelmouse-image" data-width="1440" data-height="960" />Credit: David Matos/Unsplash
<p>The hope for organoids has been that they would provide researchers a way of observing human biological process in a benign, non-invasive way. Insights regarding the manner in which human cells and organs develop a disease, progress through its stages, and respond, or not, to medication, without involving actual human subjects or animal analogues could revolutionize research.</p><p>In the case of brain organoids, researchers have been hoping they can somehow be used to reveal the secrets of neurological and neurodevelopmental disorders, including epilepsy, autism and schizophrenia.</p><p>That organoids <em>could</em> be useful—though that doesn't mean that they <em>would</em> be—as a result of their permanently remaining embryonic cells. This study is a first indicator that organoids' larger promise can actually be fulfilled. </p>An answer scientists have been hoping for
<p>"This is novel," says Geschwind. "Until now, nobody has grown and characterized these organoids for this amount of time, nor shown they will recapitulate human brain development in a laboratory environment for the most part."</p><p>Now, says first author <a href="https://geschwindlab.dgsom.ucla.edu/pages/aaron-gordon" target="_blank">Aaron Gordon</a>, "We show that these 3D brain organoids follow an internal clock, which progresses in a laboratory environment in parallel to what occurs inside a living organism. This is a remarkable finding — we show that they reach post-natal maturity around 280 days in culture, and after that begin to model aspects of the infant brain, including known physiological changes in neurotransmitter signaling."</p><p>With the study verifying a 20-month maturation process, it remains to be seen how long, or how far, maturation in organoids goes. Can their cells continue to mature for years? Decades?</p><p>Even without an answer to that question, the study, says Geschwind, "represents an important milestone by showing which aspects of human brain development are modeled with the highest fidelity and which specific genes are behaving well in vitro and when best to model them. Equally important, we provide a framework based on unbiased genomic analyses for assessing how well in vitro models model in vivo development and function."</p><p>With IPS cells able to take on the roles of so many types of cells in the human body, and the new knowledge that they do in fact mature beyond their embryonic stage, researchers can feel more confident of insights into biological mechanisms organoids seem to reveal. And researchers can now better equipped to solve some of the human body's vexing mysteries.</p>
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Inception is here: Researchers “talk” to lucid dreamers for the first time
New studies show that some people can hear and respond to questions while dreaming.
23 February, 2021
Credit: slayer87 / Adobe Stock
- Four research teams in four countries independently communicated with sleeping volunteers.
- A total of 36 participants correctly responded to questions 18.6% of the time.
- Researchers believe this could open up new avenues for treating anxiety, depression, and trauma.
<p>From Leonardo DiCaprio to Freddie Krueger, pop culture has long been fascinated with the idea of entering someone else's dreams to influence their thoughts—or steal their souls. Of course, dreams have a much longer track record than blockbuster movies. We've long been enthralled with the possibilities of what occurs when we drift off into that "other" world.</p><p>But what if that world isn't as "other" as we believed? </p><p>Unlike many studies, which are conducted by one team of researchers, four teams in four labs in four countries (France, Germany, the Netherlands, and the United States) recently attempted to communicate through dreams. The <a href="https://www.cell.com/current-biology/fulltext/S0960-9822(21)00059-2" target="_blank">results were published</a> in the journal, Current Biology. </p><p>In total, 36 volunteers—a number of lucid dreamers and some novices who claim to remember at least one dream per week—were asked a total of 158 questions. Methods of replying ranged from smiling and frowning to eye movements. The German team went so far as to request Morse code tapped out with eye patterns in a display of, as the team writes, "interactive dreaming." </p><p>While lucid dreaming dates back to at least the writings of Aristotle, the term was coined in 1913 by Dutch psychiatrist Frederik van Eeden, who identified seven types of dreams. He <a href="http://www.lucidity.com/vanEeden.html" target="_blank">believed lucid dreaming was</a> "the most interesting and worthy of the most careful observation and study." Lucid dreaming is described as the ability to take control of elements of the dream due to an awareness that you're dreaming. </p><p>A link between lucid dreams and the rapid eye movement (REM) phase of sleep was first made in 1975 by Keith Hearne. Roughly half of the population experiences at least one lucid dream in their lives, though some people regularly have them—some even train for them.</p><p>Philosophy professor Evan Thompson investigates the intersection between Buddhism and lucid dreaming in consciousness studies. In his book "Waking, Dreaming, Being," he describes what occurs when you experience metacognition—in this case, an awareness that you're awake while asleep—while dreaming. </p><p style="margin-left: 20px;">"Use your imagination to manipulate the dream. Be playful. Change things and transform them… Explore the plasticity of the dream. In this way, the mind's supple nature will manifest, and you'll gain a deeper understanding of the dreamscape as a mental construct, a product of imagination."</p>
Dream Hacking: Watch 3 Groundbreaking Experiments on Decisions, Addictions, and Sleep I NOVA I PBS
<span style="display:block;position:relative;padding-top:56.25%;" class="rm-shortcode" data-rm-shortcode-id="77f2961e9a759ae62924a8efd37a61f0"><iframe type="lazy-iframe" data-runner-src="https://www.youtube.com/embed/7M06fJxiayo?rel=0" width="100%" height="auto" frameborder="0" scrolling="no" style="position:absolute;top:0;left:0;width:100%;height:100%;"></iframe></span><p>Participants in this study certainly experienced their imagination stretching, with one volunteer "hearing" the math problem (what is eight minus six?) through a car radio while another dreamer was questioned by a movie narrator.</p><p>The results were not overwhelmingly positive mind you, yet still proved successful enough to warrant further research. One researcher called this "<a href="https://www.sciencemag.org/news/2021/02/scientists-entered-peoples-dreams-and-got-them-talking" target="_blank">proof of concept</a>" more than total confirmation. Over 60 percent of the questions went unanswered. Another 17.7 percent were unclear, while just over 3 percent answered wrong. Yet 18.6 percent of respondents were on the money, an impressive feat for the sleeping. </p><p>While the researchers aren't stealing secrets from the subconscious, they hope this discovery could open up new avenues of therapeutics in the treatment of anxiety, depression, and trauma. The idea of accessing "dream content" that they can inform with new content could lead to non-invasive forms of treatment—or "Inception."</p><p>As the team writes, </p><p style="margin-left: 20px;">"The scientific investigation of dreaming, and of sleep more generally, could be beneficially explored using interactive dreaming. Specific cognitive and perceptual tasks could be assigned with instructions presented via softly spoken words, opening up a new frontier of research."</p><p>Of course, more research is needed, though volunteers will likely not be hard to find. Peeling back the layers of consciousness is both a philosophical pursuit and a nighttime hobby, one that continues to reveal possibilities as we evolve our understanding of the unconscious. </p><p> --</p><p><em>Stay in touch with Derek on <a href="http://www.twitter.com/derekberes" target="_blank">Twitter</a> and <a href="https://www.facebook.com/DerekBeresdotcom" target="_blank" rel="noopener noreferrer">Facebook</a>. His most recent book is</em> "<em><a href="https://www.amazon.com/gp/product/B08KRVMP2M?pf_rd_r=MDJW43337675SZ0X00FH&pf_rd_p=edaba0ee-c2fe-4124-9f5d-b31d6b1bfbee" target="_blank" rel="noopener noreferrer">Hero's Dose: The Case For Psychedelics in Ritual and Therapy</a>."</em></p>
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7 dimensions of depression, explained
From baboon hierarchies to the mind-gut connection, the path to defeating depression starts with understanding its causes.
14 February, 2021
- According to the World Health Organization, more than 264 million people suffer from depression. It is the leading cause of disability and, at its worst, can lead to suicide. Unfortunately, depression is often misunderstood or ignored until it is too late.
- Psychologist Daniel Goleman, comedian Pete Holmes, neuroscientist Emeran Mayer, psychiatrist Drew Ramsey, and more outline several of the social, chemical, and neurological factors that may contribute to the complex disorder and explain why there is not a singular solution or universal "cure" that can alleviate the symptoms.
- From gaining insight into how the brain-gut connection works and adopting a more Mediterranean diet, to seeking help from medical or spiritual practitioners, depression is a personal battle that requires a personalized strategy to keep it at bay, as well as more research and understanding.
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Brain hemispheres swap memories to help you see the big picture
Scientists observe how the halves of the brain keep us informed about everything everywhere.
09 February, 2021
Credit: jolygon/Art Villone/Adobe Stock/Big Think
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<p>Imagine you're about to cross a busy street. You look right and see a car coming towards you two short blocks away. You look the other way, and no cars are coming. Should you cross? No. Why not? Because your brain retains the memory of that approaching car even when you look the other way.</p><p>The ability to remember things we're not currently looking at allows us to construct and maintain a cohesive picture in our working memory of the physical context in which we find ourselves.</p><p>"You need to know where things are in the real world, regardless of where you happen to be looking or how you are oriented at a given moment," <a href="https://picower.mit.edu/news/you-look-around-mental-images-bounce-between-right-and-left-brain" target="_blank">says</a> <a href="http://ekmillerlab.mit.edu/research/team-member/scott-brincat/" target="_blank">Scott Brincat</a>, senior author of a new study from researchers at <a href="https://picower.mit.edu" target="_blank">The Picower Institute for Learning and Memory</a> at MIT in Cambridge, Massachusetts. "But the representation that your brain gets from the outside world changes every time you move your eyes around."</p><p>The study, published in <a href="https://www.cell.com/neuron/fulltext/S0896-6273(21)00038-6" target="_blank" rel="noopener noreferrer">Neuron</a>, describes what a fancy bit of brainwork this is.</p>
Two sides of the big picture
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<p>In our working memories, the left and right hemispheres work independently when it comes to memory storage — what we see on our left is immediately stored in the right hemisphere and vice versa.</p><p>The Picower researchers have found, however, that things get substantially more interesting when we shift our gaze in the opposite direction, or if an object we're looking at moves from one side to the other.</p><p>Using our street-crossing example, when you look to the right and spot the approaching vehicle, a memory of the car is stored in our brain's left hemisphere. When you look left, a copy of that memory is quickly sent to the right hemisphere, but the copy is somehow marked in such a way that the brain understands it's not actually located on your left but is just a memory of something that's currently out of view on your right. The net result is that your working memory remains aware of traffic on both sides even when it's just looking in one direction.</p><p>"If you didn't have that," says <a href="https://picower.mit.edu/earl-k-miller" target="_blank">Earl Miller</a>, senior author of the study and in whose lab the research was conducted, "we would just be simple creatures who could only react to whatever is coming right at us in the environment, that's all. But because we can hold things in mind, we can have volitional control over what we do. We don't have to react to something now, we can save it for later."</p>Games animals play
<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yNTYyOTU2Ni9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTY3MTA4NDMwOH0.7_nXD1yRN3-MJouaRikNw54Y1MIn5j1VOYenA_GhcfE/img.jpg?width=980" id="3a8e3" class="rm-shortcode" data-rm-shortcode-id="af207311aeca3e4ad9c47bbe23092006" data-rm-shortcode-name="rebelmouse-image" data-width="1440" data-height="1077" />Credit: Eric Isselée/Adobe Stock
<p>For the study's experiments, monkeys were taught to identify onscreen objects that didn't match something they had viewed moments earlier, such as an image of a banana. To do this, they had to hold a memory of the original object in memory to make the comparison.</p><p>As this happened, researchers monitored the electrical activity of hundreds of neurons in the prefrontal cortices of both hemispheres. The researchers observed memory transfers as they happened thanks to characteristic patterns in the synchronization of brainwave frequencies that occurred each time a memory was stored, an action that takes mere milliseconds. A software decoder identified the telltale patterns.</p><p>The trials began with the monkeys staring at one side of the screen as an object appeared in the screen's center. As the monkeys perceived the object as belonging primarily to one side or the other, the researchers saw the original memory being stored in the corresponding hemisphere and a copy being made in the other.</p><p>Monkeys were also instructed at times to look from one side to the other, reassigning the central object to a new primary side as the researchers observed the memories being re-written. The speed with which monkeys could spot non-matching objects slowed down during these shifts, giving some hint of the complicated memory gymnastics going on. "It feels trivial to us, but it apparently isn't," says Miller.</p>An ensemble surprise and mystery
<p>The memory is transferred from a group, or ensemble, of neurons in one hemisphere to another ensemble on the other side. One of the surprises in the study is that even though the original memory and its copy describe the same object in the same location, they use completely different neuron ensembles on each side to represent it.</p><p>Miller notes that it used to be believed that individual neurons stored memories but that over time it became clear that groups, or ensembles, of neurons were the actual memory receptacles. Now however, if the same memory is stored in two different types of ensembles due to a difference in their role within a particular hemisphere, maybe things are even more complex than that. "Perhaps even ensembles aren't the functional units of the brain," he surmises. "So what is the functional unit of the brain? It's the computational space that brain network activity creates."</p>
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Risk-taking behavior has a unique and complex brain signature
How much of this can be linked to genetics?
31 January, 2021
Credit: Anna Shvets from Pexels
- A study on more than 12,000 test subjects finds that risk aversion is related to how much gray matter people have in their brains.
- A follow up on another 13,000 test subjects further supports the findings.
- The study is not the last word on the nature versus nurture question.
<div>We've all known that one person that has a tolerance for risk that utterly shocks everyone else. The person who will go whistling past the graveyard on their way to gamble their last dollar. To those less inclined to take such risks, it can sometimes seem like these people are from another planet.</div><p>According to new research, there is a good reason why it seems that way. People with higher tolerances for risk-taking have less gray matter in certain parts of their brains than others do, hinting at potential genetic differences as <a href="https://www.genengnews.com/news/risk-taking-behaviour-linked-to-anatomical-and-functional-differences-in-specific-brain-regions/" rel="noopener noreferrer" target="_blank">well</a>.</p>
Risky business
<p> Previous studies have reached similar conclusions but suffered from the "<a href="https://slate.com/technology/2013/05/weird-psychology-social-science-researchers-rely-too-much-on-western-college-students.html" target="_blank" rel="noopener noreferrer">WEIRD</a>" problem (Western, educated, and from industrialized, rich, and democratic countries); the college students involved in the studies were too different from the rest of the population to make the results widely applicable. For this study, published in <a href="https://www.nature.com/articles/s41562-020-01027-y" target="_blank" rel="noopener noreferrer">Nature Human Behaviour</a>, researchers were able to call upon more than 12,000 people from the <a href="https://www.ukbiobank.ac.uk/" target="_blank" rel="noopener noreferrer">UK Biobank </a>dataset of medical information from a wide variety of backgrounds. </p><p>The researchers rated participants' levels of risk aversion using self-reported levels of smoking, drinking, instances of driving over the speed limit, and tendencies to sexual promiscuity. Those who claimed to be more willing to engage in these behaviors were deemed to be more inclined to take risks.</p><p>They then compared brain scan images from the participants to their scores in search of relationships, determining that the amount of gray matter in certain parts of the brain was inversely related to the level of risk-taking a person was comfortable with.</p><p>The more gray matter, the stuff in the brain where most neurons are, the less risk they claimed to be taking. This finding remained even after controlling for gender, age, overall brain size, alcohol consumption, and handedness. </p><p>Now, this gray matter wasn't just everywhere. It was found in the amygdala and ventral striatum regions of the brain. These areas are known to be involved in decision making and risk assessment.</p><p>However, the researchers also found correlations between risk-taking and the amount of matter in the hippocampus area, which is generally associated with memory. Parts of the cerebellum, an area that controls motor function but which is also thought to have some involvement in decision making, also appear to relate to risk-taking this way.</p><p>This suggests that the neural systems behind risk-taking are more complex than previously thought. A second review of an additional 13,000 people was conducted and it confirmed these findings. </p><p>Why these areas of the brain have the gray matter they have is a complex issue, but the researchers did investigate how much of it can be attributed to genetics. The relationships between genes and behavior are extremely complex. Still, by using a system that translated genetic variations in their test subjects into a "risk score," which was tied to risky behaviors, the researchers could estimate how large a role genetics played. </p><p> They found that 3 percent of this behavior seems to be related to genetics and that 2.2 percent seems to tie directly to the genes that control gray matter in the brain. </p><p>Study co-author Philipp Koellinger commented on the genetic factor to <a href="https://penntoday.upenn.edu/news/risk-taking-behavior-has-signature-brain-big-data-shows" target="_blank" rel="noopener noreferrer">Penn Today</a>:</p><p> "We know that most behavioral traits have a complex genetic architecture, with a lot of genes that have small effects. It appears that grey matter of these three regions is translating a genetic tendency into actual behavior."</p>What does this mean, exactly? Can I blame my life choices on genetics now?
<iframe width="730" height="430" src="https://www.youtube.com/embed/mhpFpHLCuEA" frameborder="0" allow="accelerometer; autoplay; clipboard-write; encrypted-media; gyroscope; picture-in-picture" allowfullscreen></iframe><p> Despite appearances, this study doesn't settle the "nature-vs-nurture" debate in this area. As study co-author Gideon Nave told <a href="https://medicalxpress.com/news/2021-01-risk-taking-behavior-signature-brain-big.html" target="_blank" rel="noopener noreferrer">Medical Xpress</a>:</p><p> "You want to think about the fact that there are family, environment, and genetic effects, and there is also the correlation between all these factors. Genetics and environment, genetics and family—even what appears to be a genetic effect could actually be a nurture effect because you inherit your parents' genes."</p><p>He added that these findings also open up new areas for researchers looking into the questions of how genetics and brain structure interact to influence our behavior.</p><p>As with all studies about what parts of the brain are doing what, remember that we learn new things about the brain every day. While this study sheds new light on what areas are involved with risk calculations, it could turn out to only be part of a larger picture. You might not want to take this as the last word on the subject.</p><p> Though, some of you might find that a risk worth taking.</p>
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