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Human Neurons in a Dish Learn To Play Pong


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


The findings, published in Neuron, could 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 little proto-brain, whose decisions can be measured behaviourally.


Scientists from UCL Queen Square Institute of Neurology and other institutions, led by bio-tech start-up Cortical Labs, Melbourne, created a system named Dishbrain to investigate how the brain works.


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


Electrodes on the left or right of one array were then fired to tell a small number of neurons in the Dishbrain which side the ball was on, while distance from the paddle was indicated by the frequency of signals. Feedback from the electrodes enabled Dishbrain to learn how to return the ball, by making the cells act as if they themselves were the paddle — and, in consequence, moving the panel in their [simulated] world.


Although microelectrode arrays have previously been used to read the activity of brain cells, this is the first time that scientists have been able to use them to stimulate neurons in a structured way to produce responses that are realised in terms of meaningful behaviour.


Professor Karl Friston (UCL Queen Square Institute of Neurology), who was involved in the research, said: “The beautiful and pioneering aspect of this work rests on equipping the neurons with sensations – the feedback – and crucially the ability to act on their world.”


“Remarkably, the cultures learned how to make their world more predictable and have less chance of encountering surprising behaviourby acting upon it. This is remarkable because you cannot teach this kind of self-organisation; simply because – unlike a pet – these mini brains have no sense of reward and punishment.”


“The translational potential of this work is truly exciting: it means we don’t have to worry about creating ‘digital twins’ to test therapeutic interventions. We now have, in principle, the ultimate biomimetic ‘sandbox’ in which to test the effects of drugs and genetic variants – a sandbox constituted by exactly the same computing (neuronal) elements found in your brain and mine.”


By building a living model brain from basic structures in this way, scientists hope to be able to experiment using real brain function, rather than equivalent models made on a computer.


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


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


“In short, how would a ‘drunken dishbrain’ cope with playing Pong? The translational potential here is clearly relevant for psychiatric and neurological conditions that are manifest in terms of aberrant choices and behaviours (e.g., Parkinson’s disease and schizophrenia).”


The findings also raise the possibility of creating an alternative to animal testing when investigating how new drugs or gene therapies respond in these dynamic interventions.


Lead author, Dr Brett Kagan (Chief Scientific Officer, Cortical Labs) said: “We have shown we can interact with living biological neurons in a such a way that compels them to modify their activity, leading to something that resembles intelligence.”


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


Researchers hope that Dishbrain may resolve some of the bottlenecks in computer science.


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


Reference: 


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


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