Researchers at Dartmouth-Hitchcock and the Geisel School of Medicine at Dartmouth are playing a key role in a multicenter $22.5 million, four-year effort to develop next-generation technologies to restore memory function in individuals who suffer from memory loss. The project, which is in support of President Obama’s BRAIN (Brain Research through Advancing Innovative Neurotechnologies) initiative, will combine research on the basic mechanisms of memory function with the development of systems designed to electrically stimulate discrete regions of the brain.
The project, which is led by Michael Jacob Kahana, Professor of Psychology at the University of Pennsylvania, is part of the “Restoring Active Memory” program sponsored by the Defense Advanced Research Projects Agency, or DARPA.
Patients will be recruited at the Hospital of the University of Pennsylvania along with six other major medical centers: Dartmouth-Hitchcock Medical Center, Thomas Jefferson University Hospital, Emory University Hospital, University of Washington Medical Center, the Mayo Clinic, and the National Institutes of Health Clinical Center. Neuroscientists, engineers, and applied mathematicians from Boston University, Drexel University, and the University of Washington will help to develop computational models of memory and algorithms to guide brain stimulation.
A major component of this effort is the development of next-generation technologies to enable real-time recording and stimulation of sites throughout the brain. This effort will be carried out through separate collaborations with Medtronic, Inc., and Neuropace, Inc. Medtronic, whose FDA-approved deep brain stimulation systems have been implanted in more than 110,000 patients worldwide, will assist in the development of an investigational neural stimulation and monitoring system, which may lead to better understandings of the brain and how deep brain stimulation therapy can potentially restore normal brain function following injury or the onset of neuropsychological illness. Neuropace, whose RNS® System was FDA-approved in November to reduce the frequency of seizures in epilepsy patients who have not responded well to medications, will join the project to provide another platform for research in patients with implanted electrodes. By the end of the four-year project, the project aims to lay the groundwork for a fully implantable neural monitoring and stimulation system that could be used in the treatment of memory loss.
“This project will allow us to study the basis of memory in a very innovative way that will move brain stimulation ahead as a treatment modality,” says Barbara Jobst, MD, director of the Dartmouth-Hitchcock Epilepsy Center, professor of neurology at the Geisel School of Medicine and one of the principal investigators on the FDA trial that led to the approval of Neuropace. “Being part of a collaborative with a number of leading centers means that more patients can participate in this effort. We hope that what we learn not only benefits them but also helps us better understand impaired memory in general.”
“We’re very excited to participate in DARPA’s Restoring Active Memory Program,” says Duane Compton, PhD, Interim Dean at Geisel. “It illustrates the strength of our clinical and translational Neurology program.”
Because memory is the result of complex interactions between widespread brain regions, the researchers will study neurosurgical patients who have electrodes implanted in various areas of their brains for the treatment of neurological disease. By recording neural activity from these electrodes as patients play 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.
“Biomarkers of good memory function will guide our ability to stimulate the brain to synthesize patterns of neural activity conducive to proper memory function,” said Kahana. “To accomplish this we must first map the neural mechanisms of human memory in both time and space. By deciphering the unique spatiotemporal maps of good memory function in each participant we can determine how to use brain stimulation to gently coax brain activity out of dysfunctional states and towards optimal ones.”
Solving this problem will involve recruiting neurosurgical patients with epilepsy and Parkinson’s disease, who ordinarily receive brain stimulation as part of their clinical treatment. These patients may elect to participate in the projects research studies, which entail receiving safe levels of brain stimulation as they play memory games to determine if their memory can be helped by these interventions.
“If memory can be facilitated in patients who have electrodes implanted to treat epilepsy and Parkinson’s disease, and who frequently have mild memory impairment, then we will have gained extremely valuable information that we believe will be relevant to restoring normal memory function in patients with traumatic brain injury or Alzheimer’s disease,” said Kahana.
Fully anonymized data obtained during the course of this project will be made freely available “We believe sharing our anonymized data will have benefit for future research,” Kahana said, “but beyond that, we hope that all research projects involving human brain data follow this model of openness.”