Commentary

Advancing the Frontiers of Neuroscience and Neurotechnology

Lawrence Livermore National Laboratory has a long and distinguished history of working at the intersection of engineering and biology in support of national security and human health. Early accomplishments at the Laboratory included chromosome biomarkers, high-speed cell-sorting systems, and instruments for fast polymerase chain reaction. In the late 1990s, the Department of Energy (DOE) established the Chemical and Biological Weapons Nonproliferation Program, and Livermore engineers and bioscientists designed, developed, and prototyped systems to rapidly detect and diagnose a biological attack.

Laboratory researchers have continued to strengthen their expertise in biological science and engineering and micro- and nanotechnology for applications beyond biodetection. In the early 2000s, Livermore was part of a DOE effort to develop the world’s first retinal prosthesis for individuals blinded by end-stage retinitis pigmentosa. The Livermore team developed and prototyped a flexible, highly biocompatible thin-film microelectrode array and a miniaturized, biocompatible, hermetic package containing electronics for stimulating the retina with wireless power. Following successful clinical trials, this technology resulted in a commercial device, the Argus Retinal Prosthesis II, which was approved by the U.S. Food and Drug Administration (FDA) for human use.

As the feature Delving Deeply into the Brain's Mysteries describes, Livermore researchers built on the retinal prosthesis legacy in collaboration with clinical partners to develop a number of novel implantable device technologies that can diagnose and potentially treat a multitude of neural disorders. This is exemplified in the Laboratory’s current work on the development of a sense-and-treat—that is, closed-loop and autonomous—neuromodulation system that can access and address any part of the brain, providing unprecedented capability to neurosurgeons and neurologists.

More than 12 million people in the U.S. suffer from some form of serious neuropsychiatric illness—such as depression, anxiety, bipolar disorder, or schizophrenia—or disorders resulting from post-traumatic stress disorder or traumatic brain injury (TBI). Research is starting to show that these debilitating illnesses can be characterized and treated by targeting underlying specific and quantitative evaluations of dysfunctions in brain circuitry rather than subjective clinical assessments.

Deep expertise in novel biocompatible materials and state-of-the-art micro- and nanofabrication, together with advanced signal processing, computational simulation, statistical modeling, and big data analytics—all combined in a single location—give Lawrence Livermore a unique capability for studying and understanding these disorders. A dedicated fabrication and prototyping facility combines new investments of about $100 million with decades of expertise in polymer manufacturing and packaging. The Laboratory has successfully manufactured Class III implantable devices in this facility under a quality control system that can support investigational human use with the appropriate FDA approvals. In short, we have created a truly one-of-a-kind research facility to drive fundamental advances in design, development, and early clinical demonstration of implantable devices. By accurately recording brain signals in animals and humans for very long periods of time, these devices are helping to achieve a better understanding of how neurons encode, store, and retrieve information.

At the same time, Livermore researchers are continuing development of the revolutionary iChip (in vitro chip-based human investigational platform) to predict the effects of potentially harmful chemicals, viruses, and drugs on humans without resorting to animal or human test subjects. One variant is a multicellular neurovascular unit that combines brain-on-a-chip technology with an artificial blood–brain barrier to simulate the central nervous system, thereby helping scientists understand how neurons interact with and respond to chemicals. In addition, the Laboratory has partnered with medical groups nationwide to develop an understanding of the mechanisms behind chronic traumatic encephalopathy and, by leveraging the Laboratory’s unique high-performance computing capabilities, to develop improved predictive analytics for the precise diagnosis and treatment of TBI patients.

Current research thrusts are supported by a range of sponsors that include DOE; the Defense Advanced Research Projects Agency; the National Institutes of Health, through the Brain Research through Advancing Innovative Neurotechnologies Initiative; the University of California (UC), through the UC Office of the President Lab-Fee Program; and Livermore’s own Laboratory Directed Research and Development Program. Livermore is also collaborating with several leading academic institutions and private sector partners.

Today, we continue to advance human health by leveraging the Laboratory’s expertise in a truly interdisciplinary fashion. We have a tremendous opportunity to apply our know-how and extraordinary facilities to change the nation’s health care landscape.