'Big ideas' in neuroscience take on stroke, addiction and more

When making decisions about when and how to release a person from drug rehabilitation, doctors might take into account the person’s arrest history or behavior in an interview, but what they don’t consider is perhaps most central to the person’s success: their brains. How a person’s brain reacts to the thought of drugs could reveal whether he or she is ready to face the temptations of the outside world.

Or take the case of people who make important economic decisions. The amount of risk those people are willing to take can depend on their surroundings. Put them in a calm office and their choices might be different than when in an adrenaline-charged, bullpen-style environment.

Addiction and financial decision-making are two areas where policies could be improved if they took into account new research that predicts the choices people will make. Ten years ago, Brian Knutson, PhD, an associate professor of psychology, said the science of how we make decisions was too primitive to dream of a day when it could be used predict behaviors, but with new technologies things have changed.

“Sometimes we recognize that our desires are not healthy and sometimes we resist and sometimes we don’t,” Knutson said. The factors that make the difference between when we take risks or give into desires are being revealed with improved tools for understanding and imaging the brain. “Now, we really can start predicting choice,” Knutson said.

Knutson is part of an interdisciplinary team of neuroscientists, as well as faculty from economics, law, business and political science, who have created a new initiative called NeuroChoice, which has the goal of deepening our understanding of choice and extending that to optimize choices related to addiction and investment. Theirs is one of seven “big ideas” that will become prioritized initiatives of the Stanford Neurosciences Institute.

Science of decision-making

Keith Humphreys, PhD, a professor of psychiatry and behavioral sciences who has helped guide public policy related to addiction, said policies aren’t generally based on what people like Knutson and others are discovering. “What I want to do is connect the work of our scientists to public policy issues like reducing the number of people who die of addictions or lose their life savings,” he said.

Humphreys, Knutson and Robert Malenka, MD, PhD, the Nancy Friend Pritzker Professor in Psychiatry and Behavioral Sciences, are co-leading NeuroChoice, which aims to create a two-way conversation between the science of choice and the societal repercussions of those choices.

The conversation goes both ways because Humphreys said that without hearing from the people who develop policies, scientists might ask all the wrong questions. “How do doctors make decisions about who should go to detox? How do insurers decide what to cover?” he said. “If you don’t know what variables they think are important, you could do the coolest science on Earth but it would be on the wrong variables.”

Malenka, who studies addiction and reward in mice, said the collaboration extends far beyond any one faculty member’s area of expertise. “Working together, I think in five to 10 years we could have measures of brain activity that will be highly informative for decisions about treatments of addicts or predicting the probability of relapse,” he said.

Malenka added that this kind of collaboration builds on the basic research in mice that he carries out and translates into work that benefits people. “I’m hoping this will be the prototype example of how fundamental basic science research can lead to advances that in turn will have a pretty major impact on important societal issues,” he said.

Inspiring big ideas

Last winter, William Newsome, PhD, had recently become director of the new Stanford Neurosciences Institute and wanted to inspire faculty to think broadly about the intersections of neuroscience with society, engineering, medicine and other fields. What would faculty members hope to achieve if money and time were no object and potential collaborators would all say yes? He called this exercise the “big ideas in neuroscience.”

Money and time are objects, of course, but Newsome thought that if the scientists dreamed big, the institute could fund the initial stages of what would eventually become transformative new endeavors in brain research.

“The big ideas program scales up Stanford’s excellence in interdisciplinary collaboration and has resulted in genuinely new collaborations among faculty who in many cases didn’t even know each other prior to this process,” said Newsome, the Harman Family Provostial Professor and professor of neurobiology. “I was extremely pleased with the energy and creativity that bubbled up from faculty during the 'big ideas' proposal process. Now we want to empower these new teams to do breakthrough research at important interdisciplinary boundaries that are critical to neuroscience.”

The result is seven initiatives that create new interdisciplinary collaborations spanning various Stanford schools and departments. Each, like NeuroChoice, extends work already occurring at Stanford to create an initiative with broader impact than any faculty member could have alone. The initiatives fall broadly into three categories.

NeuroDiscovery initiatives intend to probe the inner workings of the brain. These include:

• NeuroChoice: Knutson (psychology), Humphreys (psychiatry) and Malenka (neurobiology and psychiatry). Probes how the brain makes decisions and expands that to influence public policy and economic decisions.
• NeuroCircuit: Amit Etkin (psychiatry) and Stephen Baccus (neurobiology). Combines a detailed understanding of brain circuits with technology that modulates neural activity to develop improved ways of treating mental health conditions.
• NeuroVision: Steve Chu (physics and molecular and cellular physiology), Liqun Luo (biology) and Tom Südhof (molecular and cellular physiology). Develops optical technologies that enable neuroscientists to visualize the brain in unprecedented detail.

NeuroEngineering initiatives tap into Stanford’s engineering faculty to create innovative new technologies for interfacing with the brain. These include:

• Brain machine interface: Kwabena Boahen (bioengineering) and E.J. Chichilnisky (neurosurgery and ophthalmology). Develops technology to interface with the brain and create intelligent prosthetics.
• NeuroFab: Nick Melosh (materials science) and Craig Garner (psychiatry). Creates an incubator for next-generation neural interface platforms.

NeuroHealth initiatives create collaborations to translate neuroscience discoveries into treatments. These include:

• Brain rejuvenation: Aaron Gitler (genetics) and Tony Wyss-Coray (neurology). Creates a center for neurodegeneration research focusing on brain maintenance and regeneration, and the role of the immune system in these processes.
• Stroke collaborative action network: Marion Buckwalter (neurology and neurosurgery) and Maarten Lansberg (neurology). Breaches barriers in our understanding of stroke to develop therapies and improve stroke recovery.