Restoring Active Memory Program Poised to Launch

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 service members 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.

Coming soon: a brain implant to restore memory

In the next few months, highly secretive US military researchers say they will unveil new advances toward developing a brain implant that could one day restore a wounded soldier’s memory.

The Defense Advanced Research Projects Agency (DARPA) is forging ahead with a four-year plan to build a sophisticated memory stimulator, as part of President Barack Obama’s $100 million initiative to better understand the human brain.

The science has never been done before, and raises ethical questions about whether the human mind should be manipulated in the name of staving off war injuries or managing the aging brain.

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The Future of Brain Implants

What would you give for a retinal chip that let you see in the dark or for a next-generation cochlear implant that let you hear any conversation in a noisy restaurant, no matter how loud? Or for a memory chip, wired directly into your brain’s hippocampus, that gave you perfect recall of everything you read? Or for an implanted interface with the Internet that automatically translated a clearly articulated silent thought (“the French sun king”) into an online search that digested the relevant Wikipedia page and projected a summary directly into your brain?

Science fiction? Perhaps not for very much longer. Brain implants today are where laser eye surgery was several decades ago. They are not risk-free and make sense only for a narrowly defined set of patients—but they are a sign of things to come.

Unlike pacemakers, dental crowns or implantable insulin pumps, neuroprosthetics—devices that restore or supplement the mind’s capacities with electronics inserted directly into the nervous system—change how we perceive the world and move through it. For better or worse, these devices become part of who we are.

Neuroprosthetics aren’t new. They have been around commercially for three decades, in the form of the cochlear implants used in the ears (the outer reaches of the nervous system) of more than 300,000 hearing-impaired people around the world. Last year, the Food and Drug Administration approved the first retinal implant, made by the company Second Sight.

Both technologies exploit the same principle: An external device, either a microphone or a video camera, captures sounds or images and processes them, using the results to drive a set of electrodes that stimulate either the auditory or the optic nerve, approximating the naturally occurring output from the ear or the eye.

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Building Better Brain Implants: The Challenge of Longevity

On August 20, JoVE, the Journal of Visualized Experiments will publish a technique from the Capadona Lab at Case Western Reserve University to accommodate two challenges inherent in brain-implantation technology, gauging the property changes that occur during implantation and measuring on a micro-scale. These new techniques open the doors for solving a great challenge for bioengineers — crafting a device that can withstand the physiological conditions in the brain for the long-term.

“We created an instrument to measure the mechanical properties of micro-scale biomedical implants, after being explanted from living animals,” explained the lab’s principal investigator, Dr. Jeffrey R. Capadona. By preserving the changing properties that occurred during implantation even after removal, the technique offers potential to create and test new materials for brain implant devices. It could result in producing longer lasting and better suited devices for the highly-tailored functions.

For implanted devices, withstanding the high-temperatures, moisture, and other in-vivo properties poses a challenge to longevity. Resulting changes in stiffness, etc, of an implanted material can trigger a greater inflammatory response. “Often, the body’s reaction to those implants causes the device to prematurely fail,” says Dr. Capadona, “In some cases, the patient requires regular brain surgery to replace or revise the implants.”

New implantation materials may help find solutions to restore motor function in individuals who have suffered from spinal cord injuries, stroke or multiple sclerosis. “Microelectrodes embedded chronically in the brain could hold promise for using neural activity to restore motor function in individuals who have, suffered from spinal cord injuries,” said Dr. Capadona.

Furthermore, Capadona and his colleagues’ method allows for measurement of mechanical properties using microsize scales. Previous methods typically require large or nano-sized samples of material, and data has to be scaled, which doesn’t always work.

When asked why Dr. Capadona and his colleagues published their methods with JoVE, he responded “We choose JoVE because of the novel format to show readers visually what we are doing. If a picture is worth [a] thousand words, a video is worth a million.”

Electrical Engineer Turns Brain Implant Research into Products

University of Utah electrical engineering professor Florian Solzbacher is helping turn science fiction into reality through his research and related startup companies. Solzbacher is pushing the boundaries of electrical devices that can be implanted into the brain and used as an interface between neurons and computers. If you’re thinking about the “Six Million Dollar Man,” you’re not entirely off base.

Solzbacher’s research builds on Utah Electrode Array (“Utah Array”) technologies, which were invented by another University of Utah professor, Richard Normann, and are recognized as the leading approach for selective communication with hundreds of neurons in the central and peripheral nervous systems. The Utah Array is a computer chip that is implanted in, and takes signals from the brain. It transmits them in a way a computer can understand – in short, a neural interface. Solzbacher has improved how the chip works and pioneered its applications.

“We are making things work,” says Solzbacher. “People have had the idea to invent better technologies like ours for years, but we are the first to make them work and get them into patients. There are over 10,000 labs worldwide that can make things with our technologies, and they, in turn, pull us in and involve us in theirs.”

Solzbacher is commercializing his research through startup company Blackrock Microsystems and sister company Blackrock NeuroMed. Both firms employ a combined 50 people and are selling their neural interface technologies and related tools to researchers and companies around the globe. Their customers are using the technologies to find new approaches for treating nervous system disorders such as blindness, deafness, Parkinson’s and epilepsy, while another set of clients is using them to control prosthetic limbs.