Solving the mysteries
of the mind
Noted neurologist Peter T. Fox, MD, has led the Health Science Center's Research Imaging Center (RIC) to world prominence in brain research since the $38 million center opened in 1991. One visiting scientist in 1995 said the center's diverse research resembled a "Manhattan Project of the mind."
Dr. Fox and his faculty have obtained impressive information about heretofore unsuspected functions of the cerebellum, and the brain's role in stuttering and depression, and have developed technologies for biomedical imaging, particularly mapping the structure and functions of the brain.
In 1996 Health Science Center researchers were involved in ground-breaking studies that challenged the way neuroscientists have thought about the cerebellum, a large portion of the brain near the brain stem. For years, scientists have known that the cerebellum is activated during movement and that injury to this part of the brain causes uncoordinated movement. The researchers used functional magnetic resonance imaging (fMRI) to record neural activity on the cerebellum during perceptual tasks accompanied by movement or not. The images confirmed the predictions of a new hypothesis arguing that the cerebellum coordinates sensory acquisition in order to assure high-quality sensory information for the rest of the brain. The images also dispelled the classical theory that the cerebellum directly controls body movement itself.
"It is rare that a study so thoroughly calls into question a century of mainstream scientific theory," said Lawrence M. Parsons, PhD, assistant professor of research at the RIC, and co-author of the paper, "Cerebellum Implicated in Sensory Acquisition and Discrimination Rather Than Motor Control," reporting the researchers' findings and published in the journal Science. In addition to Drs. Parsons and Fox, co-authors of the paper included Jia-Hong Gao (first author), assistant professor; Jinhu Xiong, PhD, instructor; Jinqi Li, former research assistant; and James Bowen, PhD, of the California Institute of Technology (Caltech).
Other research at the RIC has helped explain why antidepressant drugs don't help some severely depressed patients. Thanks to Positron Emission Tomography (PET) images, scientists can see chemical changes in the brain. "A significant number of depressed patients fail to improve with standard treatment, and there have been no reliable tests to predict which patients these will be," said Helen S. Mayberg, MD, associate professor of medicine/neurology, psychiatry and radiology. "Although there have been earlier brain imaging studies of patients with depression, and abnormalities in various areas [of the brain] were described, no clear reason for reported differences in patients has ever been defined."
The research was a combined effort of the RIC, Stephen K. Brannan, MD, assistant professor of psychiatry, and others from psychiatry. It revealed that individuals tested before treatment who had lower than normal glucose (a form of sugar) metabolism in a brain area called the rostral anterior cingulate gyrus were the ones most likely to not respond to antidepressant medication. The cingulate gyrus is one part of the limbic system, an area of the brain long thought to regulate emotions. Those with a higher than normal glucose metabolism in the same area were most likely to improve on medication.
"These findings allow us to propose a critical role for this specific region of the brain in the complex brain network used to regulate normal and abnormal mood states," Dr. Mayberg said. "They also point to the possibility of using PET results to help with diagnosis and management decisions for individual patients."
PET images also have provided researchers with insights into the causes of stuttering. "Our studies show that stuttering may be due to abnormal activations in neural systems that support speech production and hearing," noted Dr. Fox. In studies that included chronic stutterers and non-stutterers, brain images were made with participants singing, rhythmically speaking, whispering and while reading out loud in concert with others and while reading aloud individually. "What we found," Dr. Fox said, "was that during paragraph reading, while the stutterers were stuttering, they showed unusually intense cerebral and cerebellar activity, especially in the right hemisphere of the brain, and significant deactivations in the auditory system."
According to Dr. Fox, the findings suggest that self-monitoring and treatments that focus on the modification of speech production may help to overcome this disorder. Dr. Fox added, "They also highlight the neural system activations and deactivations that might be the focus of future treatments."
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