One method by which researchers can non-invasively analyze the human brain is by developing pea-sized clusters of brain cells called “mini-brains” in the research lab. This week, the team announced that they found human-like brainwaves from these organoids in a magnificent advancement of this field of research.
The movement and nerve tract development of mini-brains has been shown by the previous studies. Biologist Alysson Muotri along with the researchers at the University of California San Diego are the first to study and record human-like neural activity. The researchers wrote that they observed brain wave patterns similar to those of a developing human in their paper published in Cell Stem Cell. Muotri said that sophistication in the in vitro model is a step to help researchers to use mini-brains to study brain development, model diseases, and study about the evolution of the brain. Researchers are good at studying cancer and the heart but the brain has been behind the curve.
Researchers introduced pluripotent human stem cells to a nutrient-rich petri-dish intended to imitate the environment in which our own brains develop to create the technical “mini-brains” called organoids. These cells could be stimulated into building a 3D structure similar to the much smaller human brain because of the multipotential (potential to become any number of different cells) nature of the stem cells. The researchers started to observe the peak of neural activity from the network at around two months of development.
Co-author and Ph.D. student Richard Gao stated that at the beginning, they weren’t checking for parallels between their model and human infant when they began to observe these intermittent bursts of electrical activity. Gao said that they observed a notable feature in organoid oscillations that the network is inactive most of the time and explode spontaneously in every 10-20 seconds. This also occurs in preterm infants called trace discontinu where strong oscillatory transients emphasize the infant’s inactive ECG. He also said that we are very lucky to find a dataset reporting these features in the preterm infant EEG at a point where oscillations vary.
Muotri said that a machine learning algorithm has been prepared by the team to identify important features in the preterm infant EEGs and had it evaluate the cerebral organoids for similarities. It was able to calculate how many weeks the organoids had developed in the culture and could no more distinguish between the organoids and the infant EEGs between 25 and 40 weeks of the organoid’s development.
Muotri and the team clarified that the comparison between the two is not necessarily one-to-one and preterm infant EEGs have some limitations including the impact the thickness of a developing human skull has on readings which differ from the lab-produced organoids.
Arnold Kriegstein, a neurologist from the University of California, San Francisco, who did not contribute to the new study, said that it is difficult to state similarity between organoid activity and preterm EEG. The researchers have clearly shown the development of spontaneous activity in organoids to be reliable on the neuronal activity but organoids are very different from the actual developing cortex and we still need better evidence that the underlying mechanisms are the same even if the phenomenology is similar.
Muotri said that he can’t be sure whether the organoids were developed enough to be considered conscious and questions related to ethical dilemmas might be raised in the future. He intends to hold a meeting at UC San Diego with scientists, philosophers, and ethicists to talk about the ethical future of such technologies. He said that his tendency is always to say that technologies like blood transfusions or organ transplants, or even cars can be used for good as well as bad so brain organoids might also point in a similar direction in the future.
Journal Reference: Cell Stem Cell