The brain cells in the petri dish also play the electronic batting game Neuron

Image credit: Cortical Labs

SOURCE: CORTICAL LABS

Translated by Shilin Shu

Edited by Wei Xiao

A team of scientists led by scientists in Melbourne, Australia, has demonstrated for the first time that 800,000 brain cells living in a petri dish can perform goal-directed tasks — in this case, playing the simple tennis-like computer game "Pong.
"
The results have been published in Neuron
.

Now they want to see what happens
when the DishBrain they build, a mini-brain system, is under the influence of drugs and alcohol.

"We have shown that it is possible to interact with neurons in living organisms in this way, forcing them to modify their activities to produce something similar to intelligence," said
Dr.
Brett Kagan, first author of the paper.
He is the chief scientific officer of Cortical Labs, a biotech startup dedicated to building the next generation of biocomputer chips
.
His co-authors are affiliated with Monash University in Australia, RMIT University and University College London and the Canadian Institute for Advanced Research
.

Dr Hon Weng Chong said: "DishBrain provides an easier way to test how the brain works and provide insight into debilitating diseases
such as epilepsy and dementia.
"

Although in the past, scientists have been able to fix neurons to multi-electrode arrays and read their activity, this is the first time cells have been stimulated in a structured and meaningful way
.

"In the past, we developed brain models
based on what computer scientists thought the brain might work.
" Kagan said
.
"This is often based on our current understanding
of information technology, such as silicon computing.
"

"But actually, we don't really understand how the brain works
.
"

By building a living brain model from basic structures in this way, scientists will be able to experiment with real brain functions rather than flawed similar models
like computers.

For example, Kagan and his team will conduct the next experiment to test what effect alcohol can have
on DishBrain.

"We're trying to create a dose-response curve with ethanol — basically just getting cells 'drunk' to see if they play worse, like people do when they drink
.
" Kagan said
.

This may open a whole new door
to understanding brain activity.

"This new ability has the potential to unlock new discoveries by teaching cell cultures to perform tasks during which they exhibit the ability to perceive—to control the return of the racket through induction—that will have profound implications
for technology, health and society.
" Dr Adeel Razi, director of the Computational & Systems Neuroscience Laboratory at Monash University, said
.

"We know that the human brain has the evolutionary advantage of being adjusted
over hundreds of millions of years to survive.
Now, we seem to have been able to control and harness this incredibly powerful, and cheap biological intelligence
.
”

When studying how new drugs or gene therapies respond in these dynamic environments, this new finding also increases the possibility of
alternative animal testing.

"We also showed that stimuli can be modified based on how cells change their behavior and do this in
a real-time closed loop.
" Kagan said
.

To conduct the experiment, the team obtained neurons using mouse embryonic brains and differentiated human stem cells, which were grown on microelectrode
arrays.
These arrays of microelectrodes stimulate cells and read their activity
.

The researchers first triggered electrical stimulation on the left or right side of an array to tell which side the Dishbrain ball was on
.
The signal frequency is used to indicate the distance
of the DishBrain from the paddle.
The feedback from the electrodes causes the neurons to behave like rackets, instructing DishBrain how to hit the ball
.

"We've never seen how cells work in a virtual environment before," says Kagan.

"Now we've successfully set up a closed-loop environment to read what's going on in the cells and stimulate them with meaningful information, and then change the cells in an interactive way so they can really change each other
.
"

"The beauty and groundbreaking of this work is that it gives neurons the ability to sense—feedback—and crucially respond to the world around them," said
co-author Professor Karl Friston, a theoretical neuroscientist at University College London.

"Remarkably, these cultures learned to make their world more predictable
through action.
It's compelling because you can't teach that kind of self-organization, and it's simple — unlike pets — these mini-brains have no idea of reward and punishment," he said
.

"The translational potential of this work is really exciting
.
This means that we no longer have to worry
about creating "digital twins" of systems that test the effects of therapeutic interventions.
Now, we have the ultimate bionic sandbox in general to test the effects of drugs and genetic variants — a sandbox made up
of the exact same computing elements (neurons) found in your brains.
”

The study also supports Professor Friston's "free energy principle
.
"

"We faced challenges
when it came to studying how to guide cells along specific pathways.
Because there is no direct intervention in the dopamine system or anything else that can be used to provide specific real-time stimuli, we have to move on to a deeper level, Professor Friston's research area – information entropy – fundamental information
about how systems organize themselves on a physical level and interact with their environment.

"The free energy principle suggests that cells at this level try to minimize
unpredictability in the environment.
"

One exciting discovery, Kagan says, is that DishBrain doesn't operate
like a silicon-based system.
"When we present structured information to non-entity neurons, we see that their activity changes, which is very consistent with
their actual behavior as a dynamic system.
" He said
.

For example, neurons' ability to change and adapt to their own activity also increases over time, consistent with
what we see at cell learning rates.
”

Chong said he's excited about the discovery, but it's just the beginning
.

"It's a whole new virgin land
.
We hope that more people will join the collaboration and use the system we have built to further explore this new frontier
of science.
”

"As one of our collaborators put it, starting a new field of science is not something that happens every morning when you wake up
.
"

Original link:

style="color: #595959;text-align: left;caret-color: red;font-size: 16px;" _msthash="162189" _msttexthash="581412">Dissertation information

【】In vitro neurons learn and exhibit sentience when embodied in a simulated game-world

By Brett J.
Kagan, Andy C.
Kitchen, Nhi T.
Tran, Forough Habibollahi, Moein Khajehnejad, Bradyn J.
Parker, Anjali Bhat, Ben Rollo, Adeel Razi and Karl J.
Friston

Journal: Neuron

October 12, 2022

【DOI】https://doi.
org/10.
1016/j.
neuron.
2022.
09.
001

[Link] (22) 00806-6

Integrating neurons into digital systems may enable performance infeasible with silicon alone.
Here, we develop DishBrain, a system that harnesses the inherent adaptive computation of neurons in a structured environment.
In vitro neural networks from human or rodent origins are integrated with in silico computing via a high-density multielectrode array.
Through electrophysiological stimulation and recording, cultures are embedded in a simulated game-world, mimicking the arcade game “Pong.
” Applying implications from the theory of active inference via the free energy principle, we find apparent learning within five minutes of real-time gameplay not observed in control conditions.
Further experiments demonstrate the importance of closed-loop structured feedback in eliciting learning over time.
Cultures display the ability to self-organize activity in a goal-directed manner in response to sparse sensory information about the consequences of their actions, which we term synthetic biological intelligence.
Future applications may provide further insights into the cellular correlates of intelligence.