Human neurons in a bowl learn to play pong

Brain cells living in a bowl can perform purposeful tasks, such as playing the tennis-like computer game Pong, finds a new study involving UCL researchers.

The results, published in neuroncould have implications for future research by providing a new perspective on artificial intelligence (AI) models of how the brain works – and a basis for testing the effects of drugs on a small proto-brain whose decisions can be behaviorally measured.

Scientists from UCL’s Queen Square Institute of Neurology and others, led by Melbourne-based biotech startup Cortical Labs, have developed a system called Dishbrain to study how the brain works.

In the experiment outlined in neuron, The researchers took 800,000 brain cells from both embryonic mice and human brain cells derived from stem cells. They then grew them on microelectrode arrays that could both stimulate and read their activity.

Electrodes on the left or right side of an array were then fired to tell a small number of neurons in the dishbrain which side the ball was on, while distance from the racquet was indicated by the frequency of the signals. The feedback from the electrodes allowed Dishbrain to learn how to return the ball by making the cells behave as if they were the paddle itself – and consequently moving the panel inside her [simulated] World.

Although arrays of microelectrodes have been used before to read brain cell activity, scientists have now, for the first time, been able to use them to stimulate neurons in a structured way to elicit responses that translate into meaningful behavior.

Professor Karl Friston (UCL Queen Square Institute of Neurology), who was involved in the research, said: “The beautiful and groundbreaking aspect of this work lies in endowing the neurons with sensation – the feedback – and most importantly the ability to respond to their world to act.”

“Remarkably, cultures have learned to make their world more predictable and have fewer chances of encountering surprising behavior by reacting to it. This is remarkable because you cannot teach this type of self-organization; simply because, unlike a pet, these mini brains don’t have a sense of reward and Punishment.”

“The translational potential of this work is really exciting: it means we don’t have to worry about creating ‘digital twins’ to test therapeutic interventions. We now have what is essentially the ultimate biomimetic “sandbox” in which to test the effects of drugs and genetic variants – a sandbox made up of exactly the same (neural) computational elements found in your brain and mine.”

By building a living model brain from basic structures in this way, the scientists hope to be able to experiment with real brain functions, rather than equivalent models created on a computer.

For example, the team now hopes to use the cells to see what effect alcohol has when introduced into Dishbrain.

Professor Friston said: “The unique opportunity here is to see how the drug affects neurotransmission at the synaptic level – and more importantly, how this affects behaviour.

“In short, how would a ‘drunk cheat’ go about playing pong? The translational potential here is clearly relevant to psychiatric and neurological disorders that manifest in the form of deviant decisions and behavior (e.g. Parkinson’s and schizophrenia).”

The results also open up the possibility of creating an alternative to animal testing when studying how new drugs or gene therapies respond to these dynamic interventions.

lead author dr Brett Kagan (Chief Scientific Officer, Cortical Labs) said: “We have shown that we can interact with living biological neurons in a way that forces them to change their activity, resulting in something resembling intelligence.”

He added: “In the past, models of the brain have been developed aimed at how computer scientists think the brain might work. This is usually based on our current understanding of information technology, such as silicon computing.”

Researchers hope Dishbrain can solve some of the bottlenecks in computing.

dr Hon Weng Chong (CEO of Cortical Labs) said: “Dishbrain offers a simpler approach to test how the brain works and to gain insight into debilitating conditions such as epilepsy and dementia.”

Relation:

Kagan BJ, Kitchen AC, Tran NT, et al. In vitro neurons learn and exhibit sentience when embedded in a simulated game world. neuron. Published online October 12, 2022. doi:10.1016/j.neuron.2022.09.001

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