Human brain organoids as models for learning and intelligence
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Organoids allow animal-free study of cognitive processes
The number of people with neurodevelopmental disorders, such as autism spectrum disorders (ASD), is increasing, largely due to lifestyle changes and environmental exposures. Brain organoids allow researchers to closely model human brain development. This enables them to investigate how environmental factors like toxins and medications disrupt neural development and affect cognitive functions. This approach was recently discussed by Prof. Thomas Hartung from the Center for Alternatives to Animal Testing (CAAT) in a review article, which we summarize here.
The development of the human brain is a complex process that begins before birth and continues into early adulthood. Due to this lengthy and intricate developmental trajectory, the human brain is particularly vulnerable to environmental influences, such as chemical pollutants. Traditionally, animal testing has been used to study brain development, with pregnant mice, for example, being given certain substances to observe their effects on the brain development of their offspring. However, animal tests cannot accurately reflect human biological processes due to species differences. Simple cell cultures, where cells grow in a flat layer, are also unsuitable, as they lack the complex interactions that occur in the brain.
Brain organoids
Brain organoids are tiny, lab-grown models of the human brain that help researchers better understand the development and function of this organ. They are derived from stem cells, which are stimulated to develop into brain cells through a mixture of growth factors. These growth factors mimic the signals that occur during brain development in the embryo.
The organoids grow in a three-dimensional structure and form different cell types and layers that mimic the architecture of the human brain. This allows researchers to observe the development of brain structures and the formation of neural networks, a process that has been challenging to study until now.
Such brain organoids also provide the opportunity to study the effects of environmental toxins, nutrients, and genetic alterations directly on human cells. This enables scientists to better understand how these factors impact human health. By using stem cells from individual patients, researchers can even create personalized brain organoids, which serve as a kind of “living biopsy.” These personalized organoids are particularly useful for studying neurological disorders and individual differences in disease susceptibility.
Can organoids learn?
In animal experiments, researchers often study animal behaviour or perform invasive measurements in the animals’ brains. With brain organoids, however, it is possible to more closely examine the fundamental cellular and molecular processes essential for thinking and memory. This includes the ability of neurons to adapt to changes (synaptic plasticity) and the ways in which they connect with one another (neuronal connectivity). Cognitive functions are associated with specific brainwave patterns, such as theta and gamma waves, which can also be measured in these cell cultures. These waves indicate the coordinated activity of neurons necessary for complex cognitive processes.
How do environmental chemicals affect brain development?
Brain organoids can help trace how environmental influences can affect brain development. Studies with these models have shown that toxins acting during specific developmental stages can lead to the formation of atypical neuronal connections, which are associated with mental disorders. The use of brain organoids could also be helpful in environmental research (ecotoxicology) to study the effects of chemicals on brain development in animals, potentially replacing animal testing in this area.
Intelligent Organoids
"Organoid Intelligence" (OI) is a new approach that seeks to better understand and mimic human thinking by utilizing the computational capacity of brain organoids. Early studies show that these small brain models can function like living networks: they process information and respond to stimuli. For example, brain organoids have already been used to control robots and solve simple arithmetic tasks.
OI technologies have the potential to better explain complex cognitive processes such as perception, decision-making, memory, and emotions. By modeling these processes in brain organoids, scientists can more accurately study the foundations of these functions. At the same time, these technologies raise ethical and societal questions, as they could potentially develop consciousness and sensory perception. Researchers like Hartung advocate for responsible and clear communication to avoid both exaggerated expectations and unfounded fears.