Mini-brains attach to spinal cord and twitch muscles

A new method of growing mini-brains produces some startling results.

Mini-brains attach to spinal cord and twitch muscles
(Lancaster, et al)
  • Researchers find a new and inexpensive way to keep organoids growing for a year.
  • Axons from the study's organoids attached themselves to embryonic mouse spinal cord cells.
  • The mini-brains took control of muscles connected to the spinal cords.

Three things distinguish the lentil-sized mini-brains developed by Dr. Madeline Lancaster, of the Medical Research Council's Laboratory of Molecular Biology at Cambridge, and her colleagues.

First, a new method of supplying them nutrition has allowed the organoids to survive and continue developing for over a year. Second and third, they're the first organoids attached to spinal cords and muscle tissue, and — here's the startling part — they reached out and connected themselves to those spinal cord cells. Oh, also: They made the muscle tissue twitch.

Scientists such as Lancaster have been experimenting with organoids for a while now to improve our understanding of brain development and neurological disorders. However, her team's new research, just published in Nature Neuroscience on March 18, has, in light of these findings, taken things to another level.

How brainy is an organoid?

Before getting too creeped out, it's worth taking a moment to understand the rudimentary nature of organoids as they currently exist. The human brain is believed to contain some 100 billion neurons. The most advanced organoids so far possess just a couple of million — twice what a cockroach has and much less than an adult zebrafish. Still quite capable, but hardly human, it's becoming clearer that animals with fewer neurons than we have are likely sentient. The value of having organoids for research, however, is obvious, opening a window into all manner of human processes and diseases.

All that having been said, it can be expected that mini-brains will grow more and more sophisticated over time. This raises all sorts of ethical questions we should be addressing now, before we have a problem on our hands, if we don't already.

Happy ‘birthday,’ mini-brain

Most organoids don't grow for very long, because as the organoid grows, the nutrient solution in which it bathes can no longer reach its innermost neurons, and they die, terminating the growth cycle. In this research, scientists employed an "air-liquid interface culture." The primary purpose of the research was to verify the value of such an approach.

Each organoid was sliced into 1/2 millimeter-thick slices and attached to a membrane that was then introduced to a nutrient solution. This allowed the central neurons of each ALI-CO (for "air-liquid interface cerebral organoid") to continue receiving oxygen and nutrients. The organoids grew and produced new, healthy cells for more than one full year.

Because the ALI-COs' slice cultures were relatively easily to manipulate, the scientists were able to perform live imaging of them to assess their progress and the structures they developed. To identify the cells being produced, the team employed single-cell RNA (scRNA) sequencing to analyze six slices from three ALI-COs' cells, with an average of 4,427 cells per sample.

The live imaging revealed that axons, the nerve fibers that connect neurons, produced healthy outgrowths "reminiscent of nerve tracts" in the ALI-COs throughout the study, and various natural turning behaviors were observed. Neurons also successfully developed complex dendrites — connectors — as the organoids continued to grow. The complement of cells in the organoids was reminiscent of those in an organic embryonic brain.

Overall, the study found that that air-liquid interface culturation provides a viable, and less expensive, means of successfully growing healthy, fully-functional organoids for research purposes. The final proof of its efficacy was the spinal-cord connection.

Reach out and touch…something

As the final test of the ALI-COs' complexity, cells of spinal column attached to back muscle tissue from embryonic mice were co-cultured with the organoids.

"After 2–3 weeks in co-culture," reports the study, "dense axon tracts from the ALI-COs could be seen innervating the mouse spinal cord, and synapses were visible between human projecting axons and neurons of the mouse spinal cord." One might reasonably ask why: What did the "brain" have in "mind?" Let's hope it's simply instinctive behavior on a cellular level.

Next, the back muscles started twitching. While random muscle contraction occurs in disconnected tissue, these were much stronger, were arhythmic pulses, and could be switched off by severing the axonal connections. To further verify what seemed to be happening, researchers directly stimulated remaining axonal connections and verified their ability to produce muscle contractions. Also, the "evoked muscle contractions were intensity-dependent such that larger stimulation currents increased the amplitude of the muscle contraction." There's thus little doubt that the mini-brains were controlling the muscles connected to the spinal cords they'd reached out to and connected to. Welcome to the future.

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Credit: Getty Images
Surprising Science
  • U.S. Navy holds patents for enigmatic inventions by aerospace engineer Dr. Salvatore Pais.
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Hack your brain for better problem solving

Tips from neuroscience and psychology can make you an expert thinker.

Credit: Olav Ahrens Røtne via Unsplash
Mind & Brain

This article was originally published on Big Think Edge.

Problem-solving skills are in demand. Every job posting lists them under must-have qualifications, and every job candidate claims to possess them, par excellence. Young entrepreneurs make solutions to social and global problems the heart of their mission statements, while parents and teachers push for curricula that encourage critical-thinking methods beyond solving for x.

It's ironic then that we continue to cultivate habits that stunt our ability to solve problems. Take, for example, the modern expectation to be "always on." We push ourselves to always be working, always be producing, always be parenting, always be promoting, always be socializing, always be in the know, always be available, always be doing. It's too much, and when things are always on all the time, we deplete the mental resources we need to truly engage with challenges.

If we're serious about solving problems, at work and in our personal lives, then we need to become more adept at tuning out so we can hone in.

Solve problems with others (occasionally)

A side effect of being always on is that we are rarely alone. We're connected through the ceaseless chirps of friends texting, social media buzzing, and colleagues pinging us for advice everywhere we go. In some ways, this is a boon. Modern technologies mediate near endless opportunities for collective learning and social problem-solving. Yet, such cooperation has its limits according to a 2018 study out of Harvard Business School.

In the study, participants were divided into three group types and asked to solve traveling salesman problems. The first group type had to work on the problems individually. The second group type exchanged notes after every round of problem-solving while the third collaborated after every three rounds.

The researchers found that lone problem-solvers invented a diverse range of potential solutions. However, their solutions varied wildly in quality, with some being true light bulb moments and others burnt-out duds. Conversely, the always-on group took advantage of their collective learning to tackle more complex problems more effectively. But social influence often led these groups to prematurely converge around a single idea and abandon potentially brilliant outliers.

It was the intermittent collaborators who landed on the Goldilocks strategy. By interacting less frequently, individual group members had more time to nurture their ideas so the best could shine. But when they gathered together, the group managed to improve the overall quality of their solutions thanks to collective learning.

In presenting their work, the study's authors question the value of always-on culture—especially our submissiveness to intrusions. "As we replace those sorts of intermittent cycles with always-on technologies, we might be diminishing our capacity to solve problems well," Ethan Bernstein, an associate professor at Harvard Business School and one of the study's authors, said in a press release.

These findings suggest we should schedule time to ruminate with our inner geniuses and consult the wisdom of the crowd. Rather than dividing our day between productivity output and group problem-solving sessions, we must also create space to focus on problems in isolation. This strategy provides the best of both worlds. It allows us to formulate our ideas before social pressure can push us to abandon them. But it doesn't preclude the group knowledge required to refine those ideas.

And the more distractions you can block out or turn off, the more working memory you'll have to direct at the problem.

A problem-solving booster

The next step is to dedicate time to not dealing with problems. Counterintuitive as it may seem, setting a troublesome task aside and letting your subconscious take a crack at it improves your conscious efforts later.

How should we fill these down hours? That's up to you, but research has shown time and again that healthier habits produce hardier minds. This is especially true regarding executive functions—a catchall term that includes a person's ability to self-control, meet goals, think flexibly, and, yes, solve problems.

"Exercisers outperform couch potatoes in tests that measure long-term memory, reasoning, attention, problem-solving, even so-called fluid-intelligence tasks. These tasks test the ability to reason quickly and think abstractly, improvising off previously learned material to solve a new problem. Essentially, exercise improves a whole host of abilities prized in the classroom and at work," writes John Medina, a developmental molecular biologist at the University of Washington.

One such study, published in the Frontiers in Neuroscience, analyzed data collected from more than 4,000 British adults. After controlling for variables, it found a bidirectional relationship between exercise and higher levels of executive function over time. Another study, this one published in the Frontiers in Aging Neuroscience, compared fitness data from 128 adults with brain scans taken as they were dual-tasking. Its findings showed regular exercisers sported more active executive regions.

Research also demonstrates a link between problem-solving, healthy diets, and proper sleep habits. Taken altogether, these lifestyle choices also help people manage their stress—which is known to impair problem-solving and creativity.

Of course, it can be difficult to untangle the complex relationship between cause and effect. Do people with healthy life habits naturally enjoy strong executive functions? Or do those habits bolster their mental fitness throughout their lives?

That's not an easy question to answer, but the Frontiers in Neuroscience study researchers hypothesize that it's a positive feedback loop. They posit that good sleep, nutritious food, and regular exercise fortify our executive functions. In turn, more potent executive decisions invigorate healthier life choices. And those healthy life choices—you see where this is going.

And while life choices are ultimately up to individuals, organizations have a supportive role to play. They can foster cultures that protect off-hours for relaxing, incentivize healthier habits with PTO, and prompt workers to take time for exercise beyond the usual keyboard calisthenics.

Nor would such initiatives be entirely selfless. They come with the added benefit of boosting a workforce's collective problem-solving capabilities.

Live and learn and learn some more

Another advantage of tuning out is the advantage to pursue life-long learning opportunities. People who engage in creative or problem-solving activities in their downtime—think playing music, puzzles, and even board games—show improved executive functions and mental acuity as they age. In other words, by learning to enjoy the act of problem-solving, you may enhance your ability to do so.

Similarly, lifelong learners are often interdisciplinary thinkers. By diving into various subjects, they can come to understand the nuances of different skills and bodies of knowledge to see when ideas from one field may provide a solution to a problem in another. That doesn't mean lifelong learners must become experts in every discipline. On the contrary, they are far more likely to understand where the limits of their knowledge lie. But those self-perceived horizons can also provide insight into where collaboration is necessary and when to follow someone else's lead.

In this way, lifelong learning can be key to problem-solving in both business and our personal lives. It pushes us toward self-improvement, gives us an understanding of how things work, hints at what's possible, and, above all, gives us permission to tune out and focus on what matters.

Cultivate lifelong learning at your organization with lessons 'For Business' from Big Think Edge. At Edge, more than 350 experts, academics, and entrepreneurs come together to teach essential skills in career development and lifelong learning. Heighten your problem-solving aptitude with lessons such as:

  • Make Room for Innovation: Key Characteristics of Innovative Companies, with Lisa Bodell, Founder and CEO, FutureThink, and Author, Why Simple Wins
  • Use Design Thinking: An Alternative Approach to Tackling the World's Greatest Problems, with Tim Brown, CEO and President, IDEO
  • The Power of Onlyness: Give Your People Permission to Co-Create the Future, with Nilofer Merchant, Marketing Expert and Author, The Power of Onlyness
  • How to Build a Talent-First Organization: Put People Before Numbers, with Ram Charan, Business Consultant
  • The Science of Successful Things: Case Studies in Product Hits and Flops, with Derek Thompson, Senior Editor, The Atlantic, and Author, Hit Makers

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The Rijksmuseum employed an AI to repaint lost parts of Rembrandt's "The Night Watch." Here's how they did it.

Credit: Rijksmuseum
Culture & Religion
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