“They’re trying to do 20 years of research in 4 years,” says Michael Kahana in a tone that’s a mixture of excitement and disbelief. Kahana, director of the Computational Memory Lab at the University of Pennsylvania, is mulling over the tall order from the U.S. Defense Advanced Research Projects Agency (DARPA). In the next four years, he and other researchers are charged with understanding the neuroscience of memory and then building a prosthetic memory device that’s ready for implantation in a human brain.
DARPA’s first contracts under its Restoring Active Memory (RAM) program challenge two research groups to construct implants for veterans with traumatic brain injuries that have impaired their memories. Over 270,000 U.S. military service members have suffered such injuries since 2000, according to DARPA, and there are no truly effective drug treatments. This program builds on an earlier DARPA initiative focused on building a memory prosthesis, under which a different group of researchers had dramatic success in improving recall in mice and monkeys.
Kahana’s team will start by searching for biological markers of memory formation and retrieval. For this early research, the test subjects will be hospitalized epilepsy patients who have already had electrodes implanted to allow doctors to study their seizures. Kahana will record the electrical activity in these patients’ brains while they take memory tests.
“The memory is like a search engine,” Kahana says. “In the initial memory encoding, each event has to be tagged. Then in retrieval, you need to be able to search effectively using those tags.” He hopes to find the electric signals associated with these two operations.
Once they’ve found the signals, researchers will try amplifying them using sophisticated neural stimulation devices. Here Kahana is working with the medical device maker Medtronic, in Minneapolis, which has already developed one experimental implant that can both record neural activity and stimulate the brain. Researchers have long wanted such a “closed-loop” device, as it can use real-time signals from the brain to define the stimulation parameters.
Kahana notes that designing such closed-loop systems poses a major engineering challenge. Recording natural neural activity is difficult when stimulation introduces new electrical signals, so the device must have special circuitry that allows it to quickly switch between the two functions. What’s more, the recorded information must be interpreted with blistering speed so it can be translated into a stimulation command. “We need to take analyses that used to occupy a personal computer for several hours and boil them down to a 10-millisecond algorithm,” he says.
In four years’ time, Kahana hopes his team can show that such systems reliably improve memory in patients who are already undergoing brain surgery for epilepsy or Parkinson’s. That, he says, will lay the groundwork for future experiments in which medical researchers can try out the hardware in people with traumatic brain injuries—people who would not normally receive invasive neurosurgery.
The second research team is led by Itzhak Fried, director of the Cognitive Neurophysiology Laboratory at the University of California, Los Angeles. Fried’s team will focus on a part of the brain called the entorhinal cortex, which is the gateway to the hippocampus, the primary brain region associated with memory formation and storage. “Our approach to the RAM program is homing in on this circuit, which is really the golden circuit of memory,” Fried says. In a 2012 experiment, he showed that stimulating the entorhinal regions of patients while they were learning memory tasks improved their performance.
Fried’s group is working with Lawrence Livermore National Laboratory, in California, to develop more closed-loop hardware. At Livermore’s Center for Bioengineering, researchers are leveraging semiconductor manufacturing techniques to make tiny implantable systems. They first print microelectrodes on a polymer that sits atop a silicon wafer, then peel the polymer off and mold it into flexible cylinders about 1 millimeter in diameter. The memory prosthesis will have two of these cylindrical arrays, each studded with up to 64 hair-thin electrodes, which will be capable of both recording the activity of individual neurons and stimulating them. Fried believes his team’s device will be ready for tryout in patients with traumatic brain injuries within the four-year span of the RAM program.
Outside observers say the program’s goals are remarkably ambitious. Yet Steven Hyman, director of psychiatric research at the Broad Institute of MIT and Harvard, applauds its reach. “The kind of hardware that DARPA is interested in developing would be an extraordinary advance for the whole field,” he says. Hyman says DARPA’s funding for device development fills a gap in existing research. Pharmaceutical companies have found few new approaches to treating psychiatric and neurodegenerative disorders in recent years, he notes, and have therefore scaled back drug discovery efforts. “I think that approaches that involve devices and neuromodulation have greater near-term promise,” he says.
This article originally appeared in print as “Making a Human Memory Chip.”