Feature

Federal funding agencies wanting a return on their investment in basic research are increasingly asking basic researchers to build bridges between theory and treatment. The National Institute of Mental Health (NIMH), for example, recently created three divisions devoted entirely to funding basic research that contributes to the treatment of mental disorders--known as "translational research."

Additionally, NIMH and other institutes at the National Institutes of Health (NIH) are funding teams of investigators at new translational research centers, each of which receives up to $1.5 million each year.

What research qualifies as translational is not always clear, given that--it could be argued--any study on the human mind, brain or behavior could eventually lead to treatments for mental illness. However, by communicating and collaborating with clinicians, basic researchers can make a stronger case that their contributions may lead to treatments for mental or behavioral disorders, and, as such, are translational, says Steven Breckler, PhD, APA's executive director for science.

This translational bent extends beyond NIH, notes Breckler. The Department of Defense and many private foundations place a high priority on research that is likely to lead to future applications, he says.

While basic researchers may see this trend as alarming, they needn't be left out in the cold, Breckler notes. Those who investigate fundamental processes in the mind, brain and behavior can tap into translational funding by collaborating with clinicians to develop novel treatments or even just by answering questions about the processes of mental illness, says Bruce N. Cuthbert, PhD, a branch chief at NIMH and the primary contact for translational research in the behavioral sciences.

"What NIMH is trying to do is support basic research that has a good potential for translation," Cuthbert says. "It's a very broad term and covers a lot of basic research."

For example, one NIMH-funded project explores conditioning in rats. By refining general theories of extinction--how animals overcome existing associations--University of Vermont psychology professor Mark Bouton, PhD, hopes to contribute to new treatments for smoking cessation and anxiety disorders. Other basic researchers in the translational realm are developing interventions with clinicians for mental illnesses such as autism, anxiety disorders, schizophrenia and drug addiction.

While these researchers help develop practical applications for their knowledge, they also contribute to psychology's general body of knowledge--the basic research piece, they say. In fact, by working with clinicians and those with mental illness, psychology, anatomy and neurobiology professor Helen Tager-Flusberg, PhD, of the Boston University School of Medicine, says she has been able to broaden her general theories of social communication.

"If you are studying a particular cognitive system or a particular aspect of personality, your research will be so much more enriched by branching out and finding populations of people with related disorders," she says. "I would definitely advise basic researchers to connect with clinicians."

Clues from rats

Collaborating with clinicians isn't the only way for researchers to go translational. For example, Bouton does most of his work in the lab--using rats to learn how animals break previously learned associations. In a typical experiment, Bouton begins with a common procedure--pairing a tone and a foot-shock. Then, he seeks to decouple the animal's association through extinction. At first glance, it seems this can be achieved by simply playing the tone many times without following it up with the shock. But Bouton finds that animals do not simply overwrite the old rule--"tone precedes shock"--with the new one.

"It turns out the first learned thing is very persistent, and the second learned thing seems to be coded by the memory system as something that is an exception, a conditional exception to the rule," Bouton says.

If you place a rat into a new environment, for example, the rat will again react with fear to the tone, Bouton finds. Even shocking the rat--without playing the tone--in the old environment can reignite the association.

Instead of communicating his findings only to animal researchers, Bouton made his work translational by discussing with clinicians potential implications for human learning. Bouton realized that the persistence of old learning as demonstrated by his rats might spell bad news for those attempting to conquer panic attacks or trying to quit smoking. For example, people with a fear of airplanes can lessen that fear by sitting in an immobile airline or a room with airplane seats while practicing relaxation techniques with a therapist. However, what they are learning--that the airplane environment doesn't cue certain death--may not generalize to helicopters or different-looking airplane interiors.

Similar problems occur for those attempting to quit smoking. In a therapist's office, a smoker may learn to decouple smoking cues--such as ashtrays or even cigarettes--with the behavior of smoking, thus lessening nicotine cravings. However, once a smoker returns home to the old smoking-related environment, the learning may not hold.

With an eye toward translational findings, Bouton is exploring how to optimize extinction learning. With the support of an NIMH grant, he will use animal experiments to see whether new learning sticks better when the trials are spread out over time or when they are clustered together. In future experiments, Bouton hopes to test new drugs to see if they can enhance extinction learning.

Bouton's findings may eventually help clinicians optimize their clients' learning as well, says Cuthbert, of NIMH.

"We consider Bouton's study translational because he is doing basic research that can apply to clinical issues--anxiety disorders and smoking in particular," he says.

At least one smoking cessation therapist--Cynthia Conklin, PhD, an assistant professor of psychiatry at the University of Pittsburgh Medical Center--is taking Bouton's findings to heart. To overcome the importance of the initial learning environment uncovered by Bouton's experiments, Conklin is asking her clients to take pictures of the places they smoke, such as a back porch or bathroom. The clients then practice decoupling smoking cues from smoking behavior--by handling lighters and pretending to smoke--with those pictures displayed on a large computer screen nearby.

"Our work is largely inspired by Mark Bouton's work in that animal lab," she says.

Measuring attention

While Bouton's work could eventually lead to new smoking cessation techniques, Steven Luck, PhD, hopes his basic research will translate to new evaluations for schizophrenia treatments.

Hallucinations and other delusions may be the most dramatic symptom of schizophrenia, but problems directing attention can be equally debilitating, says Luck, a psychology professor at the University of Iowa. For example, many schizophrenic people experience uncontrollably wandering thoughts and have difficulty focusing on tasks. And while antipsychotic drugs can quiet hallucinations, no one has yet developed an intervention--behavioral or pharmacological--that addresses the attention disturbances many people with schizophrenia experience.

As a first step toward developing such interventions, Luck is extending his work exploring attention processes in normal populations to defining attention deficits experienced by those with schizophrenia. In particular, he is modifying tasks he developed with college students that parse out different forms of attention so that the tests work with mentally ill populations.

"A lot of what we do is slow the tasks down, or make the process self-paced," he says.

By doing this, Luck and his colleagues are finding that people with schizophrenia have difficulty directing their attention, though they may have no trouble paying attention once they focus on something.

A typical test by Luck demonstrates the difference. Participants look at a set of shapes displayed on a computer screen and then pick out a specific target shape--for example, a box with a gap on the side.

Preliminary results indicate that people with schizophrenia perform less well than the controls when the target is very different from the surrounding distracter shapes. Nonschizophrenic participants find this task perceptually easy, as they can scan the field and shift attention accurately to the target. When the target and distracters are similar, both patients and control participants shift attention around randomly as they search for the target, and so the two groups perform equally well.

After Luck refines such tests with a small group of participants, he sends them to researcher and clinician James Gold, PhD, a psychology and psychiatry professor at the University of Maryland School of Medicine. Gold then runs groups of about 25 people with schizophrenia and an equal number of mentally healthy participants through each new test. Luck's tests may eventually help researchers determine whether attention-focused interventions work or even help researchers determine what brain systems to target with drugs, Gold says.

"The models coming out are so much more precise at a neural level and so much more clear-cut at a cognitive level than what we had before," Gold notes.

In addition to contributing to psychological science, collaborating with Gold has helped Luck to expand his general theories of attention, Luck says. In fact, he's recently developed methods for mimicking the attention deficits of schizophrenia in normal populations. When asked to count backwards by twos while searching a scene for a given shape, normal participants' performance matches that of people with schizophrenia.

Fear of faces

Boston University's Tager-Flusberg also finds that working with clinical populations helps her flesh out her theories. Among her many interests, Tager-Flusberg studies verbal and nonverbal communication. By looking at how communication abilities break down in children with autism, she hopes to learn more about how communication happens in normal populations.

With the support of a grant from the National Institute on Deafness and Other Communication Disorders, Tager-Flusberg and her colleagues are investigating the way that autistic children "read" faces. In past research, psychologists have observed that autistic children tend to avoid looking at faces, she says. One goal of her project is to find out why.

To do this, Tager-Flusberg and her colleague Robert Joseph, PhD, will show autistic and nonautistic children pictures of people with their eyes either directed toward or away from the child. The researchers will then record the children's verbal reaction as well as their emotional reaction--as measured by a galvanic skin response meter. They will also ask the participants to judge where the pictured person is looking and time that response.

If the children with autism show more emotional activation than the others, it could mean the autistic children avoid looking at faces because faces overwhelm them. This effect could be intensified when the child feels she is being looked at, Tager-Flusberg says.

Or, if emotional reactivity does not differ between the groups, it could mean that autistic individuals simply don't understand that social information can be gleaned from faces, she says.

Should the first hypothesis hold true, therapists could focus on lessening children's anxiety when they encounter faces, says Joseph, a clinician and assistant psychology professor at Boston University. Scientists could also target pharmacological interventions to specific affective systems or neurotransmitters, such as the serotonin system, he says.

If cognitive systems seem to be driving the deficit, behavior interventions would be in order, Joseph says.

Developing interventions is not Tager-Flusberg's only goal. She hopes also to expand our understanding of how cognitive and emotional systems interact in general.

"Most people are so good at processing facial cues," she says. "You really have to see how the process breaks down to understand how it works," she says.

 

Further Reading

Have an idea for a behavioral research project, and want to make it translational? Call Bruce Cuthbert, chief of the NIMH Adult Psychopathology and Psychosocial Intervention Branch, at (301) 443-3728.

The research dollar overhaul

This article is the second in a series focusing on the changing funding climate for behavioral science research. Future articles will detail how psychologists are seeking grants from nontraditional sources and tapping into funding through large, multidisciplinary projects.