A prototype of a flat microscope, called FlatScope, has been developed as part of the Defense Advanced Research Projects Agency’s (DARPA’s) Neural Engineering System Design (NESD) project. The microscope will be designed to sit on the surface of the brain, where it will detect optical signals from neurons in the cortex. The ultimate goal of the NESD project, which includes research teams from several institutions in the U.S. and Europe, is to develop an alternate path for sight and sound to be delivered directly to the human brain. The NESD initiative has the potential to support future therapies for sensory restoration. Rice University engineers have built a lab prototype of a flat microscope they are developing as part of DARPA's Neural Engineering System Design project. The microscope will sit on the surface of the brain, where it will detect optical signals from neurons in the cortex. The goal is to provide an alternate path for sight and sound to be delivered directly to the brain. Courtesy of Rice University. Rice University researchers will develop an optical hardware/software interface that will detect signals from modified neurons, which will generate light when they are activated. The Rice project is a collaboration with the Yale University-affiliated John B. Pierce Laboratory, one of five research organizations to be awarded contracts from DARPA to support the NESD program. The John B. Pierce Laboratory team, led by neuroscientist Vincent Pieribone, is charged with developing an interface system in which modified neurons capable of bioluminescence and responsive to optogenetic stimulation can communicate with an all-optical prosthesis for the visual cortex. As part of this effort, the Rice team is charged with developing a thin interface that will monitor and stimulate hundreds of thousands — perhaps millions — of neurons in the cortex, the outermost layer of the brain. According to Rice engineers, current probes that monitor and deliver signals to neurons — to treat Parkinson’s disease or epilepsy, for example — are extremely limited. “State-of-the-art systems have only 16 electrodes, and that creates a real practical limit on how well we can capture and represent information from the brain,” professor Jacob Robinson said. For its work, the team is drawing inspiration from advances in semiconductor manufacturing, Robinson said. “We’re able to create extremely dense processors with billions of elements on a chip for the phone in your pocket. So why not apply these advances to neural interfaces?” Professor Caleb Kemere said that the Rice team was taking an all-optical approach to building an interface, where the flat microscope “might be able to visualize a million neurons.” Rice University engineering professors (from left) Ashok Veeraraghavan, Jacob Robinson and Caleb Kemere are part of a DARPA program to create a high-resolution, wireless neural interface that can be implanted on the cortex. Courtesy of Rice University. To make neurons visible to the interface, the Pierce Lab is gathering expertise in bioluminescence, with the goal of programming neurons with proteins that release a photon when triggered. “The idea of manipulating cells to create light when there's an electrical impulse is not extremely far-fetched in the sense that we are already using fluorescence to measure electrical activity,” Robinson said. Professor Richard Baraniuk, co-developer of the FlatCam. Courtesy of Jeff Fitlow/Rice University. The flat microscope is a close relation to FlatCam, developed by Rice engineers to eliminate the need for bulky lenses in cameras. Work on the FlatScope could make FlatCam even flatter — small enough to sit between the skull and cortex without putting additional pressure on the brain, and with enough capacity to sense and deliver signals from perhaps millions of neurons to a computer. Along with modifying the hardware, the team is modifying FlatCam algorithms to handle data from the brain interface. “The microscope we’re building captures three-dimensional images, so we’ll be able to see not only the surface but also to a certain depth below,” professor Ashok Veeraraghavan said. “At the moment we don’t know the limit, but we hope we can see 500 microns deep in tissue.” “That should get us to the dense layers of cortex where we think most of the computations are actually happening, where the neurons connect to each other,” Kemere said. A team at Columbia University is tackling another major challenge: the ability to wirelessly power and gather data from the interface. In its announcement, DARPA described its goals for the implantable package. According to DARPA, “Part of the fundamental research challenge will be developing a deep understanding of how the brain processes hearing, speech and vision simultaneously with individual neuron-level precision and at a scale sufficient to represent detailed imagery and sound. The selected teams will apply insights into those biological processes to the development of strategies for interpreting neuronal activity quickly and with minimal power and computational resources.” More information about the Neural Engineering System Design program is available here.