Functional Imaging: Reflections of the Brain at Work

In 1992, investigators in the Biophysics Research Institute at the Medical College of Wisconsin demonstrated that magnetic resonance imaging (MRI) could be used to measure brain function. Their discovery of functional MRI (fMRI), made simultaneously with the Massachusetts General Hospital/Harvard University and the University of Minnesota, is widely viewed as the single most important technological breakthrough in functional imaging to occur in the 1990s.

To further the development and application of this technology, which shows tremendous promise in diagnosing and monitoring almost the entire spectrum of neurological and psychiatric disorders involving the brain, the Functional Imaging Research Center (FIRC) at the Medical College was founded in 2002.

Robert C. Risinger, MD, Assistant Professor of Psychiatry and Behavioral Medicine at the Medical College, serves on the FIRC Scientific Advisory Board and is particularly enthused by the current and future mental health applications of fMRI.

“We’re looking at a variety of illnesses, from attention deficit disorder in children and adults to schizophrenia, and we’re beginning to look at fMRI in relation to bipolar disorder”, Dr. Risinger told HealthLink.

“We’re developing some of the capacity to look at this, said Dr. Risinger. “In the last couple of years we’ve been examining emotions in the brain, and looking at, for example, how women and men differ in terms of what parts of their brain are involved in experiencing emotion.

“We’ve been defining the topography of emotion (using fMRI). We’ve chosen a few particularly distinguishing emotions in men and women, in healthy people, and now we’re ready to begin to apply this in disorders of emotion.”

Stunning Array of Applications
The study of visual “reflections” of emotion, of how emotion “looks” in magnetic resonance, is but one of the many areas of fMRI research in which the Medical College has become a world leader. A primary element of FIRC’s mission is to unite basic and clinical scientists of various disciplines because the array of applications involving fMRI is stunning in its scope.

The team of investigators includes faculty members from ten Medical College areas (Anesthesiology; Biophysics Research Institute; Cell Biology, Neurobiology and Anatomy; Medicine; Neurology; Neurosurgery; Pharmacology and Toxicology; Physiology; Psychiatry and Behavioral medicine; and Radiology) as well as investigators from Marquette University and the University of Wisconsin-Milwaukee.

fMRI is being used to understand brain systems activated when healthy individuals perform sensory, motor and cognitive tasks in the scanner used for the imaging. Medical College of Wisconsin fMRI investigators have begun to apply the technique to diagnose and monitor patients with a variety of neurological and psychiatric disorders including brain tumors, stroke, epilepsy, drug abuse, Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, attention deficit disorder, multiple sclerosis, head injury, visual disorders, gastrointestinal disorders and schizophrenia.

The results have led to earlier disease detection, closer monitoring of brain conditions, and enhanced effectiveness of investigational therapies. FIRC will foster the extension of fMRI into new areas of research, such as molecular imaging.

As of 2002, MCW functional imaging research is supported by over $35 million in funding from a variety of sources including the National Institutes of Health, private foundations and industry. Approximately 25% of the clinical research projects supported by the Medical College’s General Clinical Research Center involve fMRI technology, and fMRI research at the College has resulted in ten patents that are in commercial development.

Magnetic Resonance Helps Paint a Picture
Magnetic resonance is the response of electrons, atoms, molecules or nuclei to different radiation frequencies as a result of space quantization in a magnetic field. Magnetic resonance imaging uses radio waves in a noninvasive diagnostic technique that produces computerized images of internal body tissues based on that “response.”

MRI is used, for example, to help determine if a ligament inside a knee is torn by comparing the response of the possibly injured tissue with that of the normal tissue around it. Computer imaging paints a different picture for different responses, allowing practitioners to study the results and offer diagnoses without the need for surgery at the beginning of the process. This is a more structural, anatomical view (whether something is broken) whereas fMRI offers a glimpse into function (how something is working).

The equipment used for fMRI is the same as that used for MRI. “fMRI uses a standard clinical scanner,” Dr. Risinger said. “Of course, the machine that we have is kind of tricked out, if you will. It’s a souped-up clinical machine, simply because we’re one of the world’s leaders in fMRI and we continue to press the technology. For example, the Biophysics Department here developed special pulse sequences and special coils. Think of it like special film for the camera and special lenses that allow us to take these kinds of pictures and examine things that few people can.”

Dr. Risinger used initial fMRI research into an element of bipolar disorder as but one example of the potential impact of the technology in diagnosis and treatment. “At face value, attention deficit disorder and bipolar disorder don’t appear all that similar, to a clinician at least,” said Dr. Risinger. “We’ve developed a task that looks at the ability to stop yourself from doing things. In this case it was a motor task, a button press. We train people to press the button when they see certain letters, and then we throw in these ‘lures’ to try to get them to do something that they’re not supposed to.

“We can see this is clearly applicable to attention deficit disorder, where children have a propensity to be hyperactive and do things that they’re not supposed to. It’s the inhibitory control that we’re trying to examine in attention deficit disorder. Well, we got to thinking about this after we were studying this in ADHD and we began to hypothesize. What if the general inhibition is related to certain circuits in your brain?

“So, we’ve mapped out the circuits for motor inhibition. We can actually demonstrate that certain parts of your brain are more active when you stop yourself from doing things. We thought, what if that also applies to emotions? So we developed a task to look at emotional inhibition, and we’ve just submitted an abstract of our first examination of this. It looks like it’s the same part of the brain that’s involved in the inhibition of emotion. The inhibition of emotion may be a core deficit in bipolar disorder, leading to depression or mania.”

fMRI in the Future
As fMRI plays a greater role in helping doctors distinguish nuances between disorders, it will also play a greater role in effective treatment for patients in the near future.

“We’re in the process of developing fMRI as a diagnostic tool,” Dr. Risinger said. “One of the earliest uses is going to be in stroke, for example. Even if someone is having classic symptoms of stroke, it may be difficult to detect on routine MRI or physical exams; it may be hard to tell, when someone is having a stroke, precisely where it’s occurring.

“Now that we have treatments that can be given if we catch the stroke early on, but we need to know where it’s happening and to be able to track it. We’re embarking on a large-scale study of stroke, using fMRI to examine stroke victims.

“Ultimately we’d like to extend knowledge of how the brain works into common psychiatric illnesses, for example to be better able to very accurately diagnose attention deficit or bipolar disorder. Even more specifically, for example, we’ll be able to say ‘you have problems with cognitive inhibition. So we need to kind of train, or exercise if you will, those parts of your brain by teaching you better skills, by using medications, or by a combination of treatments.’

Refining fMRI so that it becomes a tool to help treat complex psychiatric disorders and identify subtle, treatable elements within those disorders is one of the tasks ahead for that component of FIRC’s research. “I’m confident that will happen,” Dr. Risinger said. “Is it going to happen next year? No. In five years? We’re going to have a pretty good start. In ten years, I feel almost certain that we’ll be routinely using fMRI.”

Dan Ullrich
HealthLink Contributing Writer

For more on Dr. Risinger’s use of fMRI in brain imaging, see the HealthLink article Ups, Downs and In-Betweens: Manic Depression and Bipolar Disorder, One and the Same