Feature Story Summer 2013 Issue 28

Modern Thinking: The McGovern Neurotechnology Program at 7 Years

Ed Boyden holds one of his optogenetic devices. Photo: Justin Knight
Ed Boyden holds one of his optogenetic devices. Photo: Justin Knight

On a brisk sunny day in early April, McGovern Institute Director Robert Desimone and his colleague Ed Boyden looked out across the White House lawn in Washington DC. They had been invited there, along with some 75 other leading researchers, to join President Obama as he announced a new initiative to invest in technologies for brain research. In the president’s words, the new initiative will “[give] scientists the tools they need to get a dynamic picture of the brain in action and better understand how we think and how we learn and how we remember.” The so-called BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative ultimately aims to help researchers find new ways to treat, cure, and even prevent brain disorders.

While the details of the President’s initiative are still being worked out, the McGovern Institute already has a longstanding interest in neurotechnology. When Desimone became director in 2005, co-founders Patrick and Lore Harp McGovern encouraged him to establish the McGovern Institute Neurotechology (MINT) Program, to take full advantage of MIT’s many collaborative opportunities.

“For me one of the attractions of coming to MIT was the opportunity to work with people who were developing new technologies that could be revolutionary if applied to the brain,” says Desimone.

An electrode array, developed in the Boyden lab, that can record neurons in multiple circuits throughout the brain. Photo: Justin Knight

An electrode array, developed in the Boyden lab, that can record neurons in multiple circuits throughout the brain. Photo: Justin Knight

MIT, with its world-class engineering expertise, was ideally positioned for such an effort. “All that was needed was the catalyst, a way to break down barriers between engineers and neuroscientists and to speed up their interactions,” says MINT director Charles Jennings, who was recruited by Desimone to run the program. “It’s partly a matter of funding, but it’s also about connecting people and maintaining strong channels of communication.”

Today, the MINT program has supported over 25 projects, involving collaborations across at least 10 departments at MIT as well as several outside institutions. The list is eclectic, ranging from nanotechnology to neural prosthetics, from molecular genetics to management science. Among the latest projects, for example, one will explore nanodiamonds as sensors of neural activity; another will build a new superresolution microscope; and another aims to develop an implantable device for blocking nerve conduction.

“Not every project is successful, but that’s ok,” says Jennings. “We’re fortunate that we can afford to take chances on ideas that might be difficult to fund through more traditional sources. It’s a bit like venture funding — if nothing ever fails we’re probably not taking enough risks.”

MINTing New Brain Tools

Probes made in the laboratory of Michael Cima are coated with biocompatible materials to reduce inflammation (red) and scarring (green) of brain tissue. Image: Jay Sy, Kevin Spencer, Michael Cima

Probes made in the laboratory of Michael Cima are coated with biocompatible materials to reduce inflammation (red) and scarring (green) of brain tissue. Image: Jay Sy, Kevin Spencer, Michael Cima

Several years ago McGovern Investigator Ann Graybiel wanted to study deep brain structures using drugs that would target some cells but not others. But she had no way to inject tiny quantities of drugs deeply and precisely into the brain. Nor did she have the engineering expertise to devise such a tool in her own lab.

So Jennings connected her to MIT engineer Michael Cima, an expert on the design of medical devices. With the help of a seed grant from the MINT program they were able to design and build a working prototype for an “injectrode” that could inject tiny quantities of drugs with great precision, while simultaneously measuring their electrical effects at the injection site. They were later joined on the project by MIT Institute Professor Robert Langer, a renowned inventor and a longtime colleague of Cima. The three collaborators now have a multimillion dollar award from NIH to develop the technology further. They plan to test it in primate models of anxiety and depression, as a step toward eventual clinical applications.

“This is exactly what the MINT program is meant to do,” says Jennings. “We aim to support high-risk high-payoff projects, and to help researchers try new ideas quickly. We’ll give them just enough to do a pilot experiment, and if it works they are in a much stronger position to raise follow-on funding elsewhere.”

Striking a Cord

Threadlike and transparent, Polina Anikeeva’s implantable opto-electronic fibers must conform to the intricate shape of the backbone in order to reach the spinal cord.

Assistant Professor Polina Anikeeva examines a batch of fiber templates that will be extruded to form tiny opto-electronic neural probes. Photo: Justin Knight

Assistant Professor Polina Anikeeva examines a batch of fiber templates that will be extruded to form tiny opto-electronic neural probes. Photo: Justin Knight

“The technology we’re developing is uniquely suited for hard-to-access structures that are constantly moving, flexing and bending,” says Anikeeva, who is applying her expertise in materials science to create these implants in collaboration with McGovern Investigator Emilio Bizzi.

The probes, which are extruded like pasta from soft metal and transparent polymers, are capable of sending and receiving both electrical and optical signals. Though the technology is still at an early stage, in tests with mice, Anikeeva has already been able to record neural signals and stimulate nerves with light using optogenetics. “When we stimulate we can even see the leg move,” she says, excited at the progress made since she received a MINT award last year.

Once the device is mature, Anikeeva and Bizzi hope to use it to map the connections between the spinal cord and motor cortex, something that is impossible with today’s technologies. “As we are gaining more understanding, we realize we need more and more advanced tools to continue exploring,” says Anikeeva, who is also working with McGovern Investigator Guoping Feng to develop a similar probe to study mouse models of autism.

In the longer term, Anikeeva hopes the spinal probe will evolve into a neuroprosthetic device that could, someday, restore motion to individuals with severed spinal cords. “This is one of the places where optogenetics could really make a difference in people’s lives,” she says.

Engineering the Brain

Charles Jennings, director of the MINT program, helps to develop collaborations between neuroscientists and other researchers within and beyond MIT. Photo: Justin Knight

Charles Jennings, director of the MINT program, helps to develop collaborations between neuroscientists and other researchers within and beyond MIT. Photo: Justin Knight

Optogenetics has not yet been tested or approved for use in humans. But in one of the very first MINT projects, Boyden and Desimone took an important step toward that goal by applying optogenetics for the first time in non-human primates. Boyden, who subsequently joined the McGovern Institute, continues to pursue this work, and along with researchers at Massachusetts General Hospital recently published the first demonstration that optogenetics can induce behavioral effects in monkeys.

Now widely used in neuroscience research, optogenetics allows researchers to use light to control specific neurons in the living brain. In animal models of neuropsychiatric disorders such as Feng’s autistic mice, optogenetics can be used to perturb the neurons suspected to be involved, and to test ideas about how the disease might be treated. To target the light more accurately within the brain, Boyden and MIT electrical engineer Clif Fonstad have used MINT funding to develop a 3-D array of waveguides, tiny light-conducting channels with mirrored ends that can deliver light pulses in complex patterns within a targeted brain region. In future they plan to incorporate recording electrodes into their devices and to use different colors that will allow multiple types of neurons to be controlled simultaneously. “We’re trying to speak the language of the brain with light,” says Boyden.

The Big Picture

Boyden’s words echo one of the stated goals of President Obama’s Initiative, which is to create an activity map of the brain. Ultimately researchers would like to do this at the level of individual nerve impulses, but with trillions of impulses happening every second this is still a remote goal. “We need to map the forest before we try to count every tree,” says Desimone.

President Barack Obama with NIH Director Francis Collins, announcing the president's BRAIN Initiative on April 2, 2013. Official White House photo by Chuck Kennedy

President Barack Obama with NIH Director Francis Collins, announcing the president’s BRAIN Initiative on April 2, 2013. Official White House photo by Chuck Kennedy

For a 50,000-foot view of human brain activity, researchers can turn to neuroimaging. The method known as functional MRI (fMRI), for example, works by detecting local changes in cerebral blood flow, which are visible because blood contains iron. By using fMRI to scan subjects as they perform different mental tasks, researchers have been able to attribute specific functions to many different brain areas.

“But fMRI is still a very indirect way to measure brain activity,” says bioengineer Alan Jasanoff, an associate member of the McGovern Institute. “Ideally, we’d like to use MRI to look at other changes that are more directly linked to the brain’s electrical activity.”

So Jasanoff is developing new magnetic agents that will make this possible. One of his early projects was a MINT-supported collaboration with MIT chemist Stephen Lippard to develop an agent to detect calcium ions, which regulate the release of neurotransmitters. “It turned out to be harder than we hoped, but we haven’t given up yet,” says Jasanoff.

Meanwhile, his lab has developed other agents that can detect neurotransmitters such as dopamine, revealing their 3-D distribution as they are released in the living rat brain. “We’re trying to learn how the spatial and temporal patterns of specific signaling molecules relate to the functioning of the brain as a whole,” he explains.

Engineering the Future

Now that MINT has been underway for several years, it has become part of the fabric of McGovern. “Rather than simply focusing on new discoveries, we also have goals to develop the next generation of technologies for neuroscience research,” says Desimone. “And when something works, we want to make it as widely available as possible. Many of these tools will have applications that we can’t even anticipate at the outset. The more people use them, the greater the impact will be.”

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