Five questions for Tor Wager

CU-Boulder scientist works to unlock secrets of the brain

Five questions for Tor Wager
The human brain and the mechanisms surrounding its operation have intrigued scientists for generations. Now evolving technology has allowed researchers to collect and analyze data that aids the effort to unlock some brain secrets. An example: Recent groundbreaking research by Tor Wager provides a brain-activity measurement that predicts how much physical pain a person is feeling.

An associate professor of psychology and neuroscience at the University of Colorado Boulder, Wager also is director of the Cognitive and Affective Control Laboratory. His research specialties include brain imaging, placebo effects and the brain systems that involve pain, emotion and motivation. He joined CU’s faculty in 2010 but his Colorado roots extend to Evergreen, where he grew up.

“CU has been an important part of my life story as a scientist,” he said. “I’m from Colorado and the desire to come back here was motivated in part by the fact that CU is an excellent university with great colleagues and in part by that fact that I have family and friends here.”

Wager studied music as an undergraduate but wasn’t sure what would come next. He worked at a CU residence hall and took psychology classes, including some from colleagues who are still part of his department. Those professors steered him in “the right way,” pushing him to take graduate classes and to become involved in multiple research projects. He earned his Ph.D. from the University of Michigan in cognitive psychology. He then spent six years at Columbia University as an assistant and associate professor before continuing his academic career at CU-Boulder.

1. Some of your studies involve the brain and how it generates and regulates pain and emotion. One recent study found that brain patterns of physical pain and those of emotional pain are different.  What are the implications of this work?

The study came out this year in the New England Journal of Medicine and is really the first study to provide a brain measure that can predict with high accuracy, sensitivity and specificity how much physical pain someone is feeling. From a basic research perspective, the study is important because we need brain markers that are closely identified with psychological states, and there are not many examples of these. One of the major goals of neuroscience is to establish mapping between the brain and mind. We haven’t done a one-to-one mapping between a brain signature and physical pain exactly, but it’s a starting point. The study accurately tracks a specific kind of pain and that is important clinically because there are no objective measures of physical pain. This is a step toward developing such markers in patients that can actually be used and translated; it’s also important because it’s a step toward unpacking what generates pain at the brain level. We’ve identified one system, but we think there are multiple systems that make different kinds of contributions to different kinds of pain. We eventually hope to identify the brain systems that are disrupted in someone who is experiencing pain, and based on the system, know how we should treat that person.

Too often people are blamed for their pain or those in the medical community think they are faking pain or that it is all in their heads. The study will make pain connections real and help us understand the neuro-psychological basis for it.

The study also is important in another way. We need these markers if we’re going to study the impact of psychological treatments and drug treatments on pain and on emotion. Then we will be able to tell whether a brain system is affected by some – or all – classes of pain-relieving drugs and some or all kinds of psychological treatments. Psychological treatments work for pain and other emotional disorders, but they haven’t been given their due. Billions of dollars are spent on drug development while virtually nothing by comparison is spent on psychological treatments even though they work just as well. The reason is that psychology is squishy; there are no objective measures. This work can help us define objective brain processes and signatures that will allow us to study psychological phenomenon on the same footing as drug treatments and understand how they can work together.

2. Do people experience physical pain differently?

In our study, we’ve tried to carefully control a certain type of painful input. What we find is people process that similarly, to a surprising degree, so we can identify something that holds across individuals. But experiences of pain mean very different things to different people. For some people it signals disability, in some it triggers intense fear, and in others it doesn’t trigger either of these. Those aspects will be important to understanding how disabling pain is, and, for example, potentially understanding who develops chronic pain after an injury. There’s a lot of complexity and diversity in humans and understanding how different people respond differently is going to require delving into that complexity, but also pulling it apart and trying to be very systematic and scientific about it. We haven’t gotten there, but technology and this kind of work is allowing us to make progress.

3. This work will also help us understand emotional pain, correct?

One of the major frontiers in human neuroscience is to understand the ways in which we are motivated and ways in which emotional responses are generated in the brain. This frontier largely has been ignored. When the first waves of revolution in human brain science were occurring, computers were used as a metaphor, so people were interested in cognition. But we’ve realized we can come up with computational models to help us understand how brain systems and emotions work. Emotions and the regulation of emotion are so important in our lives and are often the critical part of what is disrupted in clinical disorders. For example, 20 percent of Americans are in some form of pain at any given time for a $600 billion economic impact. It’s a feature we all have to deal with and a feature of almost every disorder you can think of from cancer to strokes to back, muscle and joint pain. Other types of disorders – even schizophrenia, which people have framed as disorder of cognition – are emotional disturbances that have profound effects on functionality.

4. One area of your lab’s study is PTSD. What kind of research is being done and what have you found?

Our PTSD project is in collaboration with people in psychiatry in New York. PTSD is enormously important, especially today, but we don’t understand it well. Part of the idea is that there are multiple kinds of affective or emotional circuits. (Affect is a general term for an emotional element or ingredient.) Some of the processes people think are disruptive in PTSD are hyperactive fear response, and we’re testing that, but we’re also testing new ideas. The problem is that a person with PTSD doesn’t contextualize in the right way.

Imagine going to a movie and you see a snake on screen. You get a little startled, but you know you are safe, that it’s just a movie. Something in the brain creates this context and maintains a cognition or mental state that says, “Here I am in a movie theater. I’m safe and this is sort of fun.” If you don’t have that context or your brain doesn’t create that context in the right way, you essentially don’t learn when things are scary and when they shouldn’t be scary. People with PTSD can’t form those safety contexts and they overgeneralize. They are constantly startled and constantly anxious, have sleep disorders and fall into a spiral of disability.

5. What kind of technology has helped make some of your research possible?

We have an fMRI (functional magnetic resonance imaging) center on campus that is about a year old and enables people like me and a group of researchers to do innovative research at the intersection of brain science and psychology. We have a seed here of something that can grow into a very important initiative on campus with support.

The Intermountain Neuroimaging Consortium is a partnership between CU and the Mind Research Network in Albuquerque, N.M. The scanner helps tie together human and animal neuroscience and allows us to have collaborators in psychiatry, pain management, neurology. It also allows us to bridge departments on campus from psychology and neuroscience to electrical engineering and physics. It lets us look at how brain activity is evolving second by second. It also has enough resolution so that we can start to see what’s happening at different points in the brain and analyze relationships across brain regions.

Neuroimaging is changing the face of psychology and neuroscience. More and more animal science approaches are integrated with human brain imaging approaches. By using technology, we can discover wonderful things with wonderful precision, but it has to be integrated with models of human biology and brain function. There are so many examples of things that work beautifully in a mouse, but they don’t transfer into humans. Neuroimaging is filling the gap in translation across species.

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