September 19, 2015

DARPA's Targeted Electrical Stimulation of the Brain boosts Memory

DARPA memory research could lead to therapies for wounded warriors and others with memory deficits caused by traumatic brain injury or disease. Electrical arrays implanted in the memory centers of the brain are showing promise for their ability to help patients improve their scores on memory tests, raising hope that such approaches may someday help individuals suffering from memory deficits as a result of traumatic brain injury or other pathologies. The preliminary findings, from DARPA’s Restoring Active Memory (RAM) program, were presented in St. Louis

Just over one year into the effort, the novel approach to facilitating memory formation and recall has already been tested in a few dozen human volunteers, said program manager Justin Sanchez. The subjects in the study have neurological problems unrelated to memory loss, but volunteered to test the new neurotechnological interventions while they were undergoing brain surgery. In the study, small electrode arrays are placed in brain regions known to be involved in the formation of declarative memory—the relatively simple sort of memory used, for example, to recall lists of objects—as well as in regions involved in spatial memory and navigation.

The study aims to give researchers the ability to “read” the neural processes involved in memory formation and retrieval, and even predict when a volunteer is about to make an error in recall. The implanted electrodes also provide a means of sending signals to specific groups of neurons, with the goal of influencing the accuracy of recall.

Traumatic brain injury (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 year1, 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, few effective therapies currently exist to mitigate the long-term consequences of TBI on memory. Through the Restoring Active Memory (RAM) program, DARPA seeks to accelerate the development of technology able 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.

The end goal of RAM is to develop and test a wireless, fully implantable neural-interface medical device for human clinical use, but a number of significant advances will be targeted on the way to achieving that goal. 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.

Initial results indicate that it is indeed possible to capture and interpret key signals or “neural codes” coming from the human brain during memory encoding and retrieval, and improve recall by providing targeted electrical stimulation of the brain.

“Everyone has had the experience of struggling to remember long lists of items or complicated directions to get somewhere,” Sanchez said. “Today we are discovering how implantable neurotechnologies can facilitate the brain’s performance of these functions.”

Among other details, Sanchez said, the work is addressing the important issue of the ideal timing of electrical stimuli involved in the neural codes. “Should we provide electrical inputs when the lists are first being taught and memorized, or should we stimulate when the person is working to recall those items? We still have a lot to learn about how the human brain encodes declarative memory, but these early experiments are clarifying issues such as these and suggest there is great potential to help people with certain kinds of memory deficits,” Sanchez said.

Details about the early RAM results are being withheld for now, Sanchez said, pending peer review and publication in one or more scientific journal articles.

In related work, DARPA is about to launch a new effort to develop neurotechologies that may help individuals not just better remember individual items but learn physical skills. Complex skills can take people years to master, and it’s not just repetition of the physical movements that matters. The process also often involves the repeated mental and physiological “replaying” of the skill during wakefulness and sleep to solidify the skill. DARPA’s RAM Replay program, poised to begin in October, will aim to shed light on this replay process through a combined approach of studying direct neural and physiological interfaces, environmental cues, and the sleep-wake cycle. The selected performers will study the role of replay in the consolidation of episodic memories and newly learned skills, as well as how these memories are recalled and used by people during subsequent task performance.

Meanwhile, promising preliminary results also are coming out from DARPA’s Systems-Based Neurotechnology for Emerging Therapies (SUBNETS) program, Sanchez noted, which aims to provide relief for patients with post-traumatic stress disorder and other neuropsychiatric conditions.

Just one year into the SUBNETS effort, engineers at the Lawrence Livermore National Laboratory and Draper Laboratory have produced customized electrode arrays and miniaturized neural interface hardware, prototypes of which are on display at this week’s Wait, What? event in St. Louis. The prototypes include microfabricated electrode arrays that are flexible and can interface with large numbers of neurons; fully implantable hardware to amplify and interpret brain signals; and new circuitry to deliver precise, function-restoring feedback to the brain.

In the first clinical tests of some of these technologies, researchers at the University of California, San Francisco, placed arrays on the brains of seven patients and, by providing electrical impulses to a specific neuronal region, markedly reduced the patients’ anxiety levels.

“As the technology of these fully implantable devices improves, and as we learn more about how to stimulate the brain ever more precisely to achieve the most therapeutic effects, I believe we are going to gain a critical capacity to help our wounded warriors and others who today suffer from intractable neurological problems,” Sanchez said. “It is a very complex and challenging frontier, but one I am convinced we will learn to navigate and leverage to good effect in people who today have no effective therapeutic options.”


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