Teams will develop and test implantable therapeutic devices for memory restoration in patients with memory deficits caused by disease or trauma.
DARPA has selected two universities to initially lead the agency’s Restoring Active Memory (RAM) program, which aims to develop and test wireless, implantable “neuroprosthetics” that can help servicemembers, veterans, and others overcome memory deficits incurred as a result of traumatic brain injury (TBI) or disease.
The University of California, Los Angeles (UCLA), and the University of Pennsylvania (Penn) will each head a multidisciplinary team to develop and test electronic interfaces that can sense memory deficits caused by injury and attempt to restore normal function. Under the terms of separate cooperative agreements with DARPA, UCLA will receive up to $15 million and Penn will receive up to $22.5 million over four years, with full funding contingent on the performer teams successfully meeting a series of technical milestones. DARPA also has a cooperative agreement worth up to $2.5 million in place with Lawrence Livermore National Laboratory to develop an implantable neural device for the UCLA-led effort.
“The start of the Restoring Active Memory program marks an exciting opportunity to reveal many new aspects of human memory and learn about the brain in ways that were never before possible,” said DARPA Program Manager Justin Sanchez. “Anyone who has witnessed the effects of memory loss in another person knows its toll and how few options are available to treat it. We’re going to apply the knowledge and understanding gained in RAM to develop new options for treatment through technology.”
TBI is a serious cause of disability in the United States. Diagnosed in more than 270,000 military servicemembers since 2000 and affecting an estimated 1.7 million U.S. civilians each year, TBI frequently results in an impaired ability to retrieve memories formed prior to injury and a reduced capacity to form or retain new memories following injury. Despite the scale of the problem, no effective therapies currently exist to mitigate the long-term consequences of TBI on memory. Through the RAM program, DARPA seeks to accelerate the development of technology needed to address this public health challenge and help servicemembers and others overcome memory deficits by developing new neuroprosthetics to bridge gaps in the injured brain.
“We owe it to our servicemembers to accelerate research that can minimize the long-term impacts of their injuries,” Sanchez said. “Despite increasingly aggressive prevention efforts, traumatic brain injury remains a serious problem in military and civilian sectors. Through the Restoring Active Memory program, DARPA aims to better understand the underlying neurological basis of memory loss and speed the development of innovative therapies.”
Specifically, RAM performers aim to develop and test wireless, fully implantable neural-interface medical devices that can serve as “neuroprosthetics”—technology that can effectively bridge the gaps that interfere with an individual’s ability to encode new memories or retrieve old ones.
To start, DARPA will support the development of multi-scale computational models with high spatial and temporal resolution that describe how neurons code declarative memories—those well-defined parcels of knowledge that can be consciously recalled and described in words, such as events, times, and places. Researchers will also explore new methods for analysis and decoding of neural signals to understand how targeted stimulation might be applied to help the brain reestablish an ability to encode new memories following brain injury. “Encoding” refers to the process by which newly learned information is attended to and processed by the brain when first encountered.
Building on this foundational work, researchers will attempt to integrate the computational models developed under RAM into new, implantable, closed-loop systems able to deliver targeted neural stimulation that may ultimately help restore memory function. These studies will involve volunteers living with deficits in the encoding and/or retrieval of declarative memories and/or volunteers undergoing neurosurgery for other neurological conditions.
Unique to the UCLA team’s approach is a focus on the portion of the brain known as the entorhinal area. UCLA researchers previously demonstrated that human memory could be facilitated by stimulating that region, which is known to be involved in learning and memory. Considered the entrance to the hippocampus—which helps form and store memories—the entorhinal area plays a crucial role in transforming daily experience into lasting memories. Data collected during the first year of the project from patients already implanted with brain electrodes as part of their treatment for epilepsy will be used to develop a computational model of the hippocampal-entorhinal system that can then be used to test memory restoration in patients.
After developing an advanced, new wireless neuromodulation device—featuring ten-times smaller size and much higher spatial resolution than existing devices—the UCLA team will implant such devices into the entorhinal area and hippocampus of patients with traumatic brain injury.
The Penn team’s approach is based on an understanding that memory is the result of complex interactions among widespread brain regions. Researchers will study neurosurgical patients who have electrodes implanted in multiple areas of their brains for the treatment of various neurological conditions. By recording neural activity from these electrodes as patients play computer-based memory games, the researchers will measure “biomarkers” of successful memory function—patterns of activity that accompany the successful formation of new memories and the successful retrieval of old ones. Researchers could then use those models and a novel neural stimulation and monitoring system—being developed in partnership with Medtronic—to restore brain memory function. The investigational system will simultaneously monitor and stimulate a number of brain sites, which may lead to better understandings of the brain and how brain stimulation therapy can potentially restore normal brain function following injury or the onset of neuropsychological illness.
In addition to human clinical efforts, RAM will support animal studies to advance the state-of-the-art of quantitative models that account for the encoding and retrieval of complex memories and memory attributes, including their hierarchical associations with one another. This work will also seek to identify any characteristic neural and behavioral correlates of memories facilitated by therapeutic devices.
The performer teams are each composed of multiple universities, government research institutions, and private companies. The breadth of participation highlights the enthusiasm around the RAM program and hopes for its success.
RAM is part of a broader portfolio of programs within DARPA that support President Obama’s brain initiative. RAM’s emphasis on new discovery at a systems level reflects the great potential that lies at the heart of the president’s challenge to the neuroscience community.
RAM and related DARPA neuroscience efforts are informed by members of an independent ethical, legal, and social implications (ELSI) panel. Communications with ELSI panelists supplement the oversight provided by institutional review boards that govern human clinical studies and animal use.