Brain Imaging in Childhood and Adolescent Psychiatric Disorders
By Tonya White, M.D.
Tonya White, M.D., is a child and adolescent psychiatrist and pediatrician at the University of Minnesota. She is researching why children and adolescents develop schizophrenia and other psychotic disorders. If you are interested in learning more about the studies for children currently ongoing at the University of Minnesota, please call Jill Pluhar or Angie Guimaraes at 612-273-9835. For adult studies, please call Angie Guimaraes at 612-273-9834 or the Ambulatory Research Center at 612-627-4809.
The ability to take pictures of the living brain using computer tomography (CAT scans) and magnetic resonance imaging (MRI) has revolutionized medicine over the past 30 years. The application of these tools to study psychiatric disorders began initially in the late 1970s with CT scans, and then progressed with the advent of MRI during the 1980s. In the early 1990s, researchers at the University of Minnesota and Harvard Medical School simultaneously and independently developed a technique called functional magnetic resonance imaging (fMRI). Whereas MRI can illustrate brain structure, fMRI has the advantage of making brain function visible. For example, as you now read this article, certain areas in your brain are processing the words on this page and attempting to make sense of them. Those brain regions that you are currently using have increased blood flow to compensate for the increased brain activity. The increase in blood flow can be measured using fMRI.
 Functional Magnetic Resonance Imaging study using a Fingertapping Task |
This increased blood flow associated with different uses of the brain was actually noted in the 1920s by Dr. Harvey Cushing, a neurosurgeon in Boston. Dr. Cushing had attempted to operate on a young woman who developed gradually worsening vision due to an arterial venous malformation (AVM). An arterial venous malformation is a serious condition that shunts blood directly from the arteries to the veins. It’s like a short circuit in the vascular system and requires corrective surgery.
Surgical removal of the AVM was attempted, but unsuccessful, leaving a bony defect over the brain region involved in vision. Following the surgical attempt, Dr. Cushing found that when he placed a stethoscope over the bony defect of the skull and asked the woman to close her eyes, he could hear the turbulence caused by blood flow in the area. When he then asked her to open her eyes, the turbulence became louder. He noted that it became even louder still when he asked her to read. Thus, opening her eyes and reading caused an incremental increase in blood flow in the region of the brain involved with vision.
Measuring the changes in blood flow using fMRI are primarily research tools, although it is hoped that these studies will eventually be used for diagnosing psychiatric disorders. It is the traditional structural MRIs that are used for clinical evaluations of the brain. These studies take about 20 to 30 minutes and provide a detailed picture of the anatomy of the brain. Structural MRI is useful to make sure that the psychiatric symptoms are not a result of a neurological condition, such as brain tumors, brain malformations, or other illnesses that cause changes in brain structure.
Both structural and functional MRI are frequently used to study the biological basis of psychiatric disorders. However, these brain imaging techniques have not yet reached the sophistication necessary to diagnose psychiatric disorders. What can be done is to show differences between two groups (e.g., a schizophrenia compared to a control, or comparison, group). One finding seen consistently in children and adolescents with schizophrenia is an enlargement of the cerebral ventricles. This is a non-specific finding, meaning that it is also seen in youth with other psychiatric disorders (i.e., bipolar affective disorder) and in some children without any mental illness.
The differences in ventricular size are found when groups of patients are compared to groups of typically developing children and adolescents. For example, comparing 20 children with schizophrenia with 20 children matched by age, gender, and socioeconomic status, the children with schizophrenia will have cerebral ventricles that are about 25 percent larger than the comparison group. The cerebral ventricles are located deep within the brain and serve as a reservoir for the cerebral spinal fluid, a cushiony fluid that protects the brain and spinal cord from injury. The enlarged ventricles are thought to be a result of a loss of brain tissue in the regions surrounding the ventricles.
Another brain difference found in children, adolescents, and adults with schizophrenia is a decrease in the volume of gray matter in the brain. Gray matter, which was aptly named due to its gray appearance, forms a rim on the outer surface of the brain. It is also found in the deeper regions of the brain, or the subcortical areas. White matter, on the other hand, appears white and has a different function than gray matter. The brain signals travel fast through the white matter regions, serving like an interstate or FedEx for brain signals. The gray matter, however, is like the cities and towns, where most of the business is done prior to being shipped off to other areas.
An Axial High-Resolution Structural Image of the Brain at the Level of the Head of the Caudate |
For example, when I decide that I would like to turn the page of this MACMH article, the signals are generated in the cities, and sent quickly to other cities (or brain regions), before being FedExed down the spinal cord to move the muscles that cause me to turn the page.
So if patients with schizophrenia have, on average, less gray matter in certain regions of the brain, what does this mean? Unfortunately I cannot provide a direct answer to this question, although it is an area of considerable research, including work done at the University of Minnesota. Some studies have shown problems in the cells of the gray matter, similar to what happens when there is construction on an important bridge or intersection (i.e., construction on the Ford Bridge or Crosstown in the Twin Cities), things tend not to flow so smoothly. This lack of optimized brain activity could account for the difficulties in cognition seen in youth with schizophrenia.
Patients with schizophrenia have also been shown to have abnormalities in white matter. Sticking with the analogy, imagine how poor communication between cities could alter the activity in the cities themselves. What would happen if the interstates were gravel roads rather than paved highways and all the FedEx employees went on strike? Thus, one possibility is that the decrease in gray matter could be secondary to a primary white matter abnormality. This is an area of active research in our group at the University of Minnesota. We are using a special imaging technique known as diffusion tensor imaging that allows us to visualize nerve fiber bundles, or tracts, that travel together. White matter fibers often travel together in tracts between brain regions and down the spinal cord to the nerves of the body (i.e., those found on your finger tips).
An example of Diffusion Tensor Imaging. The white areas in the right image demonstrate where nerve fibers travel together. (Photo courtesy Dr. Xiaoping Hu, Emory University, Atlanta, GA) |
While I provide an analogy using roads, cities, and towns, I am aware that this is a vast simplification of a highly complex process. There are over 100 billion neurons in the brain, in addition to an even greater number of cells that support the neurons. There are also over 30,000 genes in the body, of which over 50 percent are expressed in the brain. Thus the brain, which weighs about 5 pounds and is less than 5 percent of our body weight, commands an enormous percentage of our genetic code, as well as an ample supply of blood.
Had the brain been simple to understand, it is unlikely that the history of individuals with psychiatric disorders would contain events such as being burned at the stake. Had the brain been simple, it is unlikely that these illnesses would have been blamed on the mother or attributed to personal weakness. On the other hand, had the brain been simple to understand humans would lack the reasoning ability required to study how the brain actually functions, the brain studying itself. The complexity of brain function is more of a blessing than a curse.
A secondary advantage in studying the complexities of brain function in relation to psychiatric disorders has been to help reduce the stigma associated with these brain illnesses. The more we know, the less foreign it becomes. The small progress made in understanding the brain is perhaps parallel to the progress made toward reducing the stigma associated with psychiatric disorders. In both, there is still much work to be done.
As researchers, our goal is to understand how a complex illness such as schizophrenia develops so that we can either prevent the onset or decrease the profound impact on those who develop the illness and their families. Brain imaging techniques serve as one tool used to understand illnesses that affect the brain, such as schizophrenia, bipolar affective disorder, obsessive compulsive disorder, major depression, and many others.
|
165 Western Avenue North
Saint Paul, MN 55102
Phone: 651-644-7333
1-800-528-4511
Fax: 651-644-7391
|
 |
|
