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Light therapy: A neuron (green) engineered to express a light-sensitive protein fires in response to specific wavelengths of light. A glass electrode (lower left corner) records the neuron’s electrical response. Researchers from Medtronic used this system to confirm that a new implantable stimulator can properly activate neurons with light.
Karl Deisseroth, Stanford University
A novel optical device could ultimately be used to treat neurological disease.
Researchers at Medtronic are developing a prototype neural implant that uses light to alter the behavior of neurons in the brain. The device is based on the emerging science of optogenetic neuromodulation, in which specific brain cells are genetically engineered to respond to light. Medtronic, the world's largest manufacturer of biomedical technologies, aims to use the device to better understand how electrical therapies, currently used to treat Parkinson's and other disorders, assuage symptoms of these diseases. Medtronic scientists say they will use the findings to improve the electrical stimulators the company already sells, but others ultimately hope to use optical therapies directly as treatments.
Today's neural implants work by delivering measured doses of electrical stimulation via a thin electrode surgically inserted through a small hole in a patient's skull, with its tip implanted in a localized brain area. Since the U.S. Food and Drug Administration approved such "brain pacer" devices and the electrically based treatment they deliver --called Deep Brain Stimulation (DBS)--for a disorder called essential tremor in 1997, for Parkinson's disease in 2002, and for dystonia in 2003, over 75,000 people have had them installed. The electrical pulses are thought to counter the abnormal neural activity that results from different diseases, though physicians know little about how DBS works.
Despite their success, such neural prostheses have serious drawbacks. Beyond the blunt fact of their physical locations, they stimulate neurons near the electrode indiscriminately. That overactivity can trigger dizziness, tingling, and other side effects. Furthermore, they produce electrical "noise" that makes tracking quieter neural signals difficult and the simultaneous use of scanning systems like MRI practically impossible, which in turn prevents researchers from gaining any evidence about how DBS actually works.
In the last few years, scientists have developed a way to stimulate neurons using light rather than electricity. Researchers first introduce a gene for a light-sensitive molecule, called channelrhodopsin 2 (ChR2), into a specific subset of neurons. Shining blue light on these neurons then causes them to fire. One advantage of this approach is its specificity--only the neurons with the gene are activated. It also provides a way to shut neurons off--introducing a different molecule, halorhodopsin (NpHR), silences the cells in response to yellow light. "That's the other unique thing about this approach," says Tim Denison, senior IC engineering manager in Medtronic's neuromodulation division. "It allows us to silence neurons' activity, which is extraordinarily difficult with electrostimulation."
While academic scientists are developing new tools to deliver light to the brain, Medtronic is developing an optogenetically based implant for commercial use. The module, which is approximately the size and shape of a small USB flash drive, has wireless data links, a power management unit, a microcontroller, and an optical stimulator. It uses a fiber-optic wire to direct light from a blue or green LED at target neurons in the brain. The company plans to market the device to neuroscience researchers and use it for in-house research on the effects of DBS.
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