“You have to begin to lose your memory, if only bits and pieces, to realize that memory is what makes our lives. Life without memory is no life at all.” — Luis Buñuel Portolés, Filmmaker

Every year, hundreds of millions of people experience the pain of a failing memory.

The reasons are many: traumatic brain injury, which haunts a disturbingly high number of veterans and football players; stroke or Alzheimer’s disease, which often plagues the elderly; or even normal brain aging, which inevitably touches us all.

Memory loss seems to be inescapable. But one maverick neuroscientist is working hard on an electronic cure. Funded by DARPA, Dr. Theodore Berger, a biomedical engineer at the University of Southern California, is testing a memory-boosting implant that mimics the kind of signal processing that occurs when neurons are laying down new long-term memories.

The revolutionary implant, already shown to help memory encoding in rats and monkeys, is now being tested in human patients with epilepsy — an exciting first that may blow the field of memory prosthetics wide open.

To get here, however, the team first had to crack the memory code.

Deciphering Memory

From the very onset, Berger knew he was facing a behemoth of a problem.

We weren’t looking to match everything the brain does when it processes memory, but to at least come up with a decent mimic, said Berger.

“Of course people asked: can you model it and put it into a device? Can you get that device to work in any brain? It’s those things that lead people to think I’m crazy. They think it’s too hard,” he said.

But the team had a solid place to start.

The hippocampus, a region buried deep within the folds and grooves of the brain, is the critical gatekeeper that transforms memories from short-lived to long-term. In dogged pursuit, Berger spent most of the last 35 years trying to understand how neurons in the hippocampus accomplish this complicated feat.

At its heart, a memory is a series of electrical pulses that occur over time that are generated by a given number of neurons, said Berger. This is important — it suggests that we can reduce it to mathematical equations and put it into a computational framework, he said.

Berger hasn’t been alone in his quest.

By listening to the chatter of neurons as an animal learns, teams of neuroscientists have begun to decipher the flow of information within the hippocampus that supports memory encoding. Key to this process is a strong electrical signal that travels from CA3, the “input” part of the hippocampus, to CA1, the “output” node.

This signal is impaired in people with memory disabilities, said Berger, so of course we thought if we could recreate it using silicon, we might be able to restore — or even boost — memory.

Bridging the Gap

Yet this brain’s memory code proved to be extremely tough to crack.

The problem lies in the non-linear nature of neural networks: signals are often noisy and constantly overlap in time, which leads to some inputs being suppressed or accentuated. In a network of hundreds and thousands of neurons, any small change could be greatly amplified and lead to vastly different outputs.

It’s a chaotic black box, laughed Berger.

With the help of modern computing techniques, however, Berger believes he may have a crude solution in hand. His proof?

Use his mathematical theorems to program a chip, and then see if the brain accepts the chip as a replacement — or additional — memory module.

Berger and his team began with a simple task using rats. They trained the animals to push one of two levers to get a tasty treat, and recorded the series of CA3 to CA1 electronic pulses in the hippocampus as the animals learned to pick the correct lever. The team carefully captured the way the signals were transformed as the session was laid down into long-term memory, and used that information — the electrical “essence” of the memory — to program an external memory chip.

They then injected the animals with a drug that temporarily disrupted their ability to form and access long-term memories, causing the animals to forget the reward-associated lever. Next, implanting microelectrodes into the hippocampus, the team pulsed CA1, the output region, with their memory code.

The results were striking — powered by an external memory module, the animals regained their ability to pick the right lever.

Encouraged by the results, Berger next tried his memory implant in monkeys, this time focusing on a brain region called the prefrontal cortex, which receives and modulates memories encoded by the hippocampus.

Placing electrodes into the monkey’s brains, the team showed the animals a series of semi-repeated images, and captured the prefrontal cortex’s activity when the animals recognized an image they had seen earlier. Then with a hefty dose of cocaine, the team inhibited that particular brain region, which disrupted the animal’s recall.

Next, using electrodes programmed with the “memory code,” the researchers guided the brain’s signal processing back on track — and the animal’s performance improved significantly.

A year later, the team further validated their memory implant by showing it could also rescue memory deficits due to hippocampal malfunction in the monkey brain.

A Human Memory Implant

Last year, the team cautiously began testing their memory implant prototype in human volunteers.

Because of the risks associated with brain surgery, the team recruited 12 patients with epilepsy, who already have electrodes implanted into their brain to track down the source of their seizures.

Repeated seizures steadily destroy critical parts of the hippocampus needed for long-term memory formation, explained Berger. So if the implant works, it could benefit these patients as well.

The team asked the volunteers to look through a series of pictures, and then recall which ones they had seen 90 seconds later. As the participants learned, the team recorded the firing patterns in both CA1 and CA3 — that is, the input and output nodes.

Using these data, the team extracted an algorithm — a specific human “memory code” — that could predict the pattern of activity in CA1 cells based on CA3 input. Compared to the brain’s actual firing patterns, the algorithm generated correct predictions roughly 80% of the time.

It’s not perfect, said Berger, but it’s a good start.

Using this algorithm, the researchers have begun to stimulate the output cells with an approximation of the transformed input signal.

We have already used the pattern to zap the brain of one woman with epilepsy, said Dr. Dong Song, an associate professor working with Berger. But he remained coy about the result, only saying that although promising, it’s still too early to tell.

Song’s caution is warranted. Unlike the motor cortex, with its clear structured representation of different body parts, the hippocampus is not organized in any obvious way.

It’s hard to understand why stimulating input locations can lead to predictable results, said Dr. Thoman McHugh, a neuroscientist at the RIKEN Brain Science Institute. It’s also difficult to tell whether such an implant could save the memory of those who suffer from damage to the output node of the hippocampus.

“That said, the data is convincing,” McHugh acknowledged.

Berger, on the other hand, is ecstatic. “I never thought I’d see this go into humans,” he said.

But the work is far from done. Within the next few years, Berger wants to see whether the chip can help build long-term memories in a variety of different situations. After all, the algorithm was based on the team’s recordings of one specific task — what if the so-called memory code is not generalizable, instead varying based on the type of input that it receives?

Berger acknowledges that it’s a possibility, but he remains hopeful.

I do think that we will find a model that’s a pretty good fit for most conditions, he said. After all, the brain is restricted by its own biophysics — there’s only so many ways that electrical signals in the hippocampus can be processed, he said.

“The goal is to improve the quality of life for somebody who has a severe memory deficit,” said Berger. “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.”

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