Brain Organoids Grown In Lab Show Neural Activity Similar To Preterm Infants

This is a cross-section of a brain organoid, showing the initial formation of a cortical plate. Each color marks a different type of brain cell. Image credit: Muotri Lab-UCTV

Brain blobs the size of a pea have begun to show signs of neural activity similar to those of preterm infants. The team say this is an "unprecedented" level of brain waves seen in vitro. 

"Never in the history of science has anyone shown brain cells firing and connecting such as we have seen with our organoids. So, there was no precedent to compare," lead author Alysson Muotri told IFLScience. 

"I was very skeptical when I saw the results. Like many neuroscientists, I had the wrong assumption that an artificially made human brain organoid would never reach this level of sophistication. This is mainly because brain organoids do not have all cell types, do not have all brain regions, are not vascularized, etc."

Dubbed "mini-brains" for simplicity’s sake, these organoids often conjure images of shrunken, wrinkled noggins growing consciousness in a sterile lab. Instead, these mini-organoids look like fleshy dots in a dish, a collection of brain cells that are beginning to show electrical patterns similar to those of preterm babies. Therefore, "brain organoids" is perhaps a better name for what we have here, say the UC San Diego team.

"The organoids have ~1 million neurons and a real brain several billions, so size is significantly smaller," added Muotri.

"We developed a new brain organoid protocol where neurons can dynamically connect over time, forming a network that is much more mature and active than everything previously reported by science. Not only that, because the activity is so high, we start detecting oscillatory brain waves, similar to the ones measured by EEGs."

The brain organoids went from producing 3,000 spikes per minute to 300,000 electrical impulses per minute.

These pea-size brain organoids are 10 months old. Image credit: Muotri Lab-UCTV

These waves of activity are the necessary forerunners for the brain to process sophisticated information and control actions, behaviors, and more. To achieve such a result, published today in the journal Cell Stem Cell, the team coaxed human stem cells to grow into cortex tissue and fostered them in a culture mimicking that of a developing brain.

As the organoids began to grow, the team recorded any and all electrical patterns, revealing consistent increases in activity over the months, including spontaneous network formation. The team then used a machine-learning algorithm to compare the neural activity of the organoids to 39 premature babies between 6 and 9.5 months old. 

"We generated a machine-learning algorithm that can precisely determine the age of the subject based on EEG features. This machine was trained with real data and can distinguish EEGs from preterm babies from 25-38 weeks post-conception," added Muotri. "We next feed the machine with the comparable data coming from our in vitro brain organoid at different weeks. The machine gets very confused with the organoid data and can no longer distinguish the real EEG data coming from the human brain from the data coming from the organoids."

Brain organoids in a laboratory dish. UC San Diego Health Sciences

First and foremost, their work shows that the emergence of these intricate networks and brain oscillatory waves is genetically programmed. "It does not depend on cues coming from the environment in utero. Also, the cortex alone can do it, and we don’t need all brain regions connected for them to emerge," said Muotri.

"Second, as we get models that are similar to the human brain, more ethical questions will appear. Our work should reframe the ethical discussions in this field. While we don’t have any evidence of 'cognition,' 'consciousness,' or 'self-aware' on these brain organoids, we should discuss how to measure it and what to do if positive."

For now, these brain organoids show no signs of consciousness. However, determining when an organoid has surpassed that line is a predicament in itself, especially when we have no defined way to measure consciousness in adults or humans. 

The purpose of such a study is to investigate the beginnings of the human brain, not to eventually replace one. The work could inform research into brain diseases that affect millions of people worldwide but currently lack an existing animal model.

Other applications include human development during early stages of embryogenesis, how the human brain evolved from our ancestral and other species, improved AI algorithms, and "to study the impact of the environment and microorganisms in the human brain (such as we did with the Zika virus)."

This activity map generated by multi-electrode arrays reveals how active the brain organoid is. Red means very active and black means silent. Image credit: Muotri Lab-UCTV
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