Scientists created mini brains that behave like real human brains

A midbrain organoid in a petri dish. The black pigment is neuromelanin, a hallmark of the human midbrain. Credit: Image courtesy of The Agency for Science, Technology and Research (A*STAR)

Original article appeared on Tonic Vice.

It’s the first time that brain organoids have spontaneously produced brain waves similar to human brain activity.

Scientists are now able to grow organoids, or mini versions of different organs, in petri dishes. They can make mini hearts, livers, or placentas, but perhaps the most intriguing are mini brains.

Brain organoids are made from human pluripotent stem cells, which are cells that can become any kind of cell in the adult body. When the stem cells are introduced to certain chemicals, they can be coaxed into becoming brain cells, then put into a liquid with the nutrients they need to survive.

“The amazing thing is that, after this, they pretty much do everything alone,” says Alysson Muotri, a molecular biologist at UC San Diego. The cells self-assemble into spheres that contain neural progenitor cells, or cells that will become brain cells. Over the course of a few weeks, those cells turn into different kinds of neurons that can act just like neurons in the human brain.

In a study preprint published on bioRxiv and presented at the Society for Neuroscience conference last month, Muotri and his colleagues reported that they recorded spontaneous and complex electrical activity from their lab-grown mini brains. It’s the first time that brain organoids have spontaneously produced brain waves similar to human brain activity,Nature reported.

“The EEG measurements were very dynamic over time,” Muotri says. At first, Muotri and his collaborators detected some electrical signals, followed by a long pause when the brain organoids were silent. Eventually, the time between activity became shorter and shorter. Then, the brain oscillations started to become synchronized, firing all together. After that, they noticed the signals becoming less synchronized and more complex.

Mini brain organoid, with layered neural tissue and different groups of neural stem cells (in blue, red and magenta) giving rise to neurons (green).

Over the course of six months, the brain organoids continued to increase their firing patterns. When they compared the electrical activity of the mini brains to that of premature babies, the mini brain’s patterns looked similar to infants born at 25 to 39 weeks.

“This dynamic evolution of the networks is very similar to what happens to the human developing brain,” Muotri says. “We never expected that the brain organoids would reach this last level, because it requires a lot of neuronal activity and nobody has reported this before in vitro.”

Does this mean that brain organoids are conscious? If they’re showing electrical activity… are they thinking? Most likely, no. For now, there aremany differences between a mini brain and a human brain. A brain organoid doesn’t contain all the other brain cell types a human has and importantly, it’s not connected to anything—like a body. Still, it’s an important question that researchers will have to keep in mind as they continue to develop the organoid technology.

Christof Koch, president and chief scientific officer of the Allen Institute for Brain Science and author of several books on consciousness, told Naturethat, “The closer they get to the preterm infant, the more they should worry.”

12 weeks with a new pet resulted in “major improvements” for some people with treatment-resistant depression
A new study in the Journal of Psychiatric Research found what—anecdotally—many know to be true: Having a pet can be an enriching emotional experience. So much so, that they found it might enhance care for people with treatment resistant major depressive disorder.

“These patients need alternative therapeutic options since they are resistant to pharmacological treatment, and there is a need to think of other approaches, non-pharmacological, to help the patients get better,” says Jorge Mota Pereira, a psychiatrist at Clínica Médico-Psiquiátrica da Ordem in Portugal and first author on the paper.

In a group of 80 patients, Pereira asked who would be willing to adopt a pet, and 33 people adopted either a cat or dog. (20 ended up with dogs, and seven with a cat.)

At the end of 12 weeks, the people who got pets had major improvements in their depression symptoms—more than 30 percent responded or went into remission, which is when depression symptoms completely disappear. “Given these were treatment-resistant patients, the sole fact that more than 30 percent responded or remitted shows that pets are being very positive for the patients,” Pereira tells me.

The researchers can’t quantify exactly why it worked, but Pereira says that one reason might be that pets might counteract one of the main symptoms of depression: anhedonia, or an inability to experience pleasure from everyday activities someone once found enjoyable.

“By having the responsibility of taking care of an animal, people have to get up in the morning to take care of the animal, namely pet them and feed them. In the specific case of dogs, the need of taking a dog for a walk, hike and run promote physical activity and could help its owner to meet new people that also have pets, sharing experiences and improve the social skills.”

It’s important to say that pets are not a cure for depression—every person in the study also remained on their medication—and that the benefit of a pet would only occur in people who like animals, and have the time, attention, and money to care for them.

There might now be a more accessible way to tell if a person in a vegetative state is conscious
When a person is in a vegetative state, often from a severe brain injury, they don’t respond to their environment or other people. Even though they’re awake, they’re not considered to be aware.

But just because the body isn’t moving doesn’t necessarily mean someone is “brain dead.” A study in Science from 2006 found that a vegetative patient who was asked to imagine “playing tennis or moving around her home” showed much more brain activity than expected. When in an fMRI, her brain looked about the same as a healthy person’s brain who was asked to think about the the same things.

“The findings indicated that this patient and others like her may have hidden cognitive abilities,” The Scientist wrote.

Since then, physicians have had to grapple with determining whether their patients are truly in a vegetative state, conscious, or somewhere in between. In a study in Current Biology, a new approach uses electroencephalogram, or EEG, to ask: Is anybody home? Our brains have a very specific response to human speech, but it wasn’t known if seeing the response to speech on an EEG in a vegetative patient could be a good proxy for the fMRI scanning. (The problem with putting every person in a vegetative state into an fMRI is that it’s costly and time-consuming; an EEG can be done quickly and at the bedside.)

So the researchers looked at the EEGs of 21 severely brain-injured patients listening to the sound of human speech. The patients ranged in their severity: 12 were in a “minimally conscious state,” three were in a “vegetative state,” and six were “emerged from minimally conscious state,” meaning they had some limited ability to move and communicate.

“The patients listened to personally meaningful narratives spoken to them by family members,” says Nicholas Schiff, a brain injury specialist at Weill Cornell Medicine and senior author on the paper. Their brain activity was compared to 13 healthy people listening to Alice’s Adventures in Wonderland read out loud.

Then, the brain-injured patients were brought to the fMRI and asked to do mental imagery tasks like “‘imagine swinging a tennis racket with your right hand,” or “keep opening and closing your right hand,” the paper says.

They found that the patients who could do the fMRI mental imagery tasks also had the most similar to normal EEG responses to spoken speech, Schiff tells me. “It showed that they understood high-level language commands and could sustain attention, working memory and mental planning of actions, all high level conscious behaviors that they could not demonstrate through movements,” he says.

This method might not replace the fMRI imaging completely, but it could reliably help determine which vegetative patients should be imaged for cognitive activity.

“We do not have a screening method that can identify patients who might harbor such capacities and to be able to selectively study such persons with fMRI and further follow up may help bring more resources to aid their recovery of communication with the outside world,” Schiff says. “In more acute setting these tools may be important in the intensive care unit as recent work by other suggests that prognosis is impacted positively when such hidden capacities are present.”

People smelled phantom “onion-like” smells when nerves in their nose were electrically stimulated
Whenever I get a cold, I’m reminded of the importance of smell to transform food from mush into an enjoyable sensory experience. Lucky for me, my sense of smell eventually returns, but for a large group of people with smell disorders, it doesn’t get better. About 5 percent of Americans have anosmia, which is a complete loss of smell, and many more—at least 20.5 million—have some other kind of olfactory disorder that impairs their smelling. Also, even if you don’t have a smell disorder now, for most people, smell gets worse with age.

“The overall impact on people with smell loss is variable,” says Eric Holbrook, chief of the rhinology division at Massachusetts Eye and Ear and an associate professor of otolaryngology at Harvard Medical School. “Some are bothered by it enough to contribute to depression. Never being able to again smell flowers, the seaside, perfume, wine, etc. has a big impact on quality of life that most of us don’t realize until we lose it.”

In a new study, researchers at Massachusetts Eye and Ear have been able to induce the sense of smell for the first time, and they did it by putting electrodes into the nose and stimulating nerves in a part of the brain where smell is processed.

When you smell something, it’s because your nose detects chemicals in the air and those chemicals stimulate olfactory neurons in your nasal cavity. Those neurons are located high in the nose and they send information across the skull base to a brain structure called the olfactory bulb. From there, the signal goes to other parts of the brain where the sensation of a smell is processed.

“In many cases of smell loss, most experts feel that there is a large loss of olfactory neurons in the nose that is the cause,” Holbrook tells me. “If this is true, then perhaps we can bypass the nasal cavity neurons and directly stimulate the olfactory bulb through electrical signals to restore smell in people who lost the sensation.”

In the new study, people reported experiencing smells that were “onion-like,” or generally described as “bad” and “antiseptic-like.” These smells are similar to what’s described in another smell disorder called phantosomia—where people smell something that’s not there.

“The reason for the type of smell in both cases may be a result of widespread electrical activity that may be over-stimulating the system,” Holbrook says. “It would be like putting thousands of odors together in a jar, opening the lid, and smelling the contents–probably not going to be a good or recognizable smell.”

More study is needed to refine the stimulation, but this technique could one day lead to a kind of implant in the nose that could restore the sense of smell—like a hearing aid, but a smelling aid.

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