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18:13 25 October 2004

The world's first brain prosthesis has passed the first stages of live testing.

The microchip, designed to model a part of the brain called the hippocampus, has been used successfully to replace a neural circuit in slices of rat brain tissue kept alive in a dish. The prosthesis will soon be ready for testing in animals.

The device could ultimately be used to replace damaged brain tissue which may have been destroyed in an accident, during a stroke, or by neurodegenerative conditions such as Alzheimer's disease. It is the first attempt to replace central brain regions dealing with cognitive functions such as learning or speech.

To achieve their result, Theodore Berger and his colleagues at the University of Southern California in Los Angeles, US, had to develop a system that would “read” real neural signals from healthy tissue, process them just as the lost brain tissue should, and pass on the resulting signals to the next brain area.

The brain region they are trying to replace is the hippocampus, which is vital for forming memories. The hippocampus has a well-understood three-part circuit. It also has a regular repeating structure, so elements of all three parts of the hippocampal circuit can be kept in a fully functional state, even in small slices in a culture dish.

Mathematical mimicry
In previous work, Berger's team had recorded exactly what biological signals were being produced in the central part of the hippocampal circuit and had made a mathematical model to mimic its activity. They then programmed the model onto a microchip, roughly 2 millimetres square (New Scientist, 12 March 2003).

Now the team has tested whether its chip can work like the real thing. They cut out the central part of the circuit in real rat brain slices and used a grid of miniature electrodes to feed signals in and out of their microchip. “We asked if output from an intact slice was the same as from a slice with the substituted chip,” says Berger. “The answer was yes. It works really well.”

The signals produced by the intact brain slice and the prosthetic hippocampus matched in shape, timing and statistics, the team revealed at the Society for Neuroscience meeting in San Diego on Sunday.

“It proves you can take out a piece of a central brain region - a piece with real clinical interest - replace it with a chip, and get it to operate as it did before,” said Berger.

Long-range connections
The team are now working towards testing their prosthetic device on a live rat, which they expect to do within three years. They are also developing a mathematical model of primate hippocampal activity, so that they can eventually move on to testing the device in monkeys.

Guenter Gross, at the University of North Texas in Denton, is impressed with the approach, but adds “the problem will be how to make the long-range connections". Even if the device can replace the local connections, he suggests, the hippocampus makes connections to many different brain regions. “There are intricate, complicated connections formed during development that cannot be replaced,” he says.

Another problem is that when a region of the brain is damaged, immune cells and brain cells called glia migrate into the damaged site. They will affect any attempt to bypass or replace the damaged tissue, says Gross.

However, Berger says the team are developing special electrodes coated with proteins that should mimic healthy tissue and repel the unwanted cells. There's no reason why this approach couldn't be used to replace any region of the brain, says Berger. “We see this as a very general approach.”

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