Berger began working with Vasilis Marmarelis, a biomedical engineer at USC, to begin making a brain prosthesis. They first worked with hippocampal slices from rats. Knowing that neuronal signals move from one end of the hippocampus to the other, the researchers sent random pulses into the hippocampus, recorded the signals at various locales to see how they were transformed, and then derived mathematical equations describing the transformations. They implemented those equations in computer chips.
Next, to assess whether such a chip could serve as a prosthesis for a damage hippocampal region, the researchers investigated whether they could bypass a central component of the pathway in the brain slices. Electrodes placed in the region carried electrical pulses to an external chip, which performed the transformations normally done in the hippocampus. Other electrodes delivered the signals back to the slice of brain.
Then the researchers took a leap forward by trying this in live rats, showing that a computer could in fact serve as an artificial component of the hippocampus. They began by training the animals to push one of two levers to receive a treat, recording the series of pulses in the hippocampus as they chose the correct one. Using those data, Berger and his team modeled the way the signals were transformed as the lesson was converted into a long-term memory, and they captured the code believed to represent the memory itself. They proved that their device could generate this long-term memory code from input signals recorded in rats’ brains while they learned the task. Then they gave the rats a drug that interfered with their ability to form long-term memories, causing them to forget which lever produced the treat. When the researchers pulsed the drugged rats’ brains with the code, the animals were again able to choose the right lever.
Last year, the scientists published primate experiments involving the prefrontal cortex, a part of the brain that retrieves the long-term memories created by the hippocampus. They placed electrodes in the monkey brains to capture the code formed in the prefrontal cortex that they believed allowed the animals to remember an image they had been shown earlier. Then they drugged the monkeys with cocaine, which impairs that part of the brain. Using the implanted electrodes to send the correct code to the monkeys’ prefrontal cortex, the researchers significantly improved the animal’s performance on the image-identification task.
Within the next two years, Berger and his colleagues hope to implant an actual memory prosthesis in animals. They also want to show that their hippocampal chips can form long-term memories in many different behavioral situations. These chips, after all, rely on mathematical equations derived from the researchers’ own experiments. It could be that the researchers were simply figuring out the codes associated with those specific tasks. What if these codes are not generalizable, and different inputs are processed in various ways? In other words, it is possible that they haven’t cracked the code but have merely deciphered a few simple messages.
Berger allows that this may well be the case, and his chips may form long-term memories in only a limited number of situations. But he notes that the morphology and biophysics of the brain constrain what it can do: in practice, there are only so many ways that electrical signals in the hippocampus can be transformed. “I do think we’re going to find a model that’s pretty good for a lot of conditions and maybe most conditions,” he says. “The goal is to improve the quality of life for somebody who has a severe memory deficit. If I can give them the ability to form new long-term memories for half the conditions that most people live in, I’ll be happy as hell, and so will be most patients.”
Despite the uncertainties, Berger and his colleagues are planning human studies. He is collaborating with clinicians at his university who are testing the use of electrodes implanted on each side of the hippocampus to detect and prevent seizures in patients with severe epilepsy. If the project moves forward as envisioned, Berger’s group will piggyback on the trial to look for memory codes in those patients’ brains.
