Last fall, Geoffrey Ling, a top biotechnology research official at the Defense Advanced Research Projects Agency (DARPA), challenged neuroscientists to do something extraordinary: Develop an implantable device that can restore memory loss in vets with traumatic brain injuries. Offering up to $40 million in short-term, high-stakes funding, Ling said, “Here's the golden ring—who's brave enough to step up and actually grab it?”
Today, DARPA announced two academic teams that will spend the next 4 years attempting to meet that challenge as part of President Barack Obama’s roughly $110 million Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative. Researchers at the University of California, Los Angeles (UCLA), will receive up to $15 million to develop a memory-restoring prosthesis that focuses on the entorhinal cortex and hippocampus—brain regions key to memory formation. A second team at the University of Pennsylvania (UPenn) will receive up to $22.5 million to develop a device that can monitor and modulate many different brain regions involved in memory formation and storage.
Some researchers, however, are skeptical that the efforts will make major headway on such a complicated problem.
Both the UCLA team, led by neurosurgeon Itzhak Fried, and the UPenn team, led by neuroscientist Michael Kahana, will start out by studying neuronal activity in people with epilepsy, who are often recruited for brain stimulation studies because they were already treated through open-brain surgery. Fried will build on his earlier work in epileptic patients, which has shown that stimulating the entorhinal cortex improves performance on a computer game that requires players to quickly learn and remember where to drop off taxi passengers in a virtual city. Next, he will use data from those studies to build computational models of how the entorhinal cortex and hippocampus work together to convert daily experiences into lasting memories.
Kahana also aims to develop a computational model of memory formation, but using a different approach. By searching the brains of epileptic patients for electrical “biomarkers” of memory retrieval and storage, he hopes to build a program that can detect when memory goes awry and instruct a device to help repair it.
The U.S. Department of Energy’s Lawrence Livermore National Laboratory in California and the device manufacturer Medtronic will also contribute to the efforts, aiming to build neurostimulators at least 10 times smaller than previous devices. Contractual agreements about rights to the technologies are still under way, according to DARPA officials.
If successful, the researchers ultimately hope to conduct the first clinical trials of deep brain stimulation in people with traumatic brain injury. That’s a “very achievable and realizable” goal because the teams are building on solid existing research in people and animals, says James Giordano, a neuroscientist at Georgetown University in Washington, D.C., who serves as a neuroethics adviser to DARPA’s BRAIN-related efforts.
The viability of the DARPA effort will depend greatly on what kind of memory loss people with traumatic brain injury actually have, says Roger Redondo, a neuroscientist at the Massachusetts Institute of Technology in Cambridge. Memory loss can result from problems with either storage or retrieval, he notes. In the case of a storage problem, the connections that form a memory were either never formed to begin with, or were destroyed, he says. In such cases, “no implantable device is going to help.”
On the other hand, if a traumatic injury produces a retrieval problem, in which most of a memory is there, but simply difficult to access, stimulation could potentially be useful, he says. “It is going to be extremely hard,” however, to determine which cells contain the memory and precisely tune electrical stimulation to drive its retrieval, he says. “The complexity of the brain, and the hippocampus, is such that any change in voltage that a microelectrode or chip can apply, even in a tiny area, will affect multitudes of neurons in uncontrolled ways,” he says.
Relying too heavily on epilepsy as a model for traumatic brain injury could also be problematic, says neuropsychologist James Sumowski of the Kessler Foundation in West Orange, New Jersey. Although some people with such injuries go on to develop epilepsy, most don’t show the same patterns of abnormal electrical activity or areas of atrophy that epileptic patients do, he says. “They are very different disorders.”
On the bright side, such challenges define the kind of “blue-sky, high-risk” project that DARPA is uniquely positioned to take on, Redondo says. Given the 270,000 veterans of the Iraq and Afghanistan wars who have been diagnosed with traumatic brain injury, nothing less than a major scientific leap is required, says Justin Sanchez, program manager for DARPA’s memory restoration program. As things stand, the options for injured service members “are very few.”
*Correction, 11 July, 12:10 p.m.: A previous version of this story attributed the final quote by Justin Sanchez to Geoffrey Ling. The story has been corrected.