UW Medicine Report to the Community

When you turn the pages of this report, your hands and brain engage in silent communication. Learning how the nervous system commands muscles to move has been a career-long pursuit of Dr. Marjorie Anderson, professor and vice chair of rehabilitation medicine and professor of physiology and Biophysics.

Anderson started out as a medical technologist at Wayne County General Hospital in Eloise, Mich.. She came to the UW as a National Science Foundation fellow in the Department of Physiology and Biophysics. Although she had decided against becoming a physician, she remained interested in medical conditions. While a UW graduate student researching brain cells, she frequently went on hospital rounds with a neurologist. On the wards she wondered about the mechanisms of neurological diseases.

"I gravitated toward movement disorders, especially Parkinson's disease and the parts of the brain associated with it, "Anderson said. "I wanted to know why the brain produced the abnormal movements common to Parkinson's."

Her earliest work was on signaling among nerve cells. She was among the scientists recording the electrical activity of a collection of neurons, known as the basal ganglia, located deep inside the brain. These neurons participate in governing movement.

When clinical researchers began performing corrective surgery or implanting electronic stimulators to reduce the tremors of Parkinson's, Anderson had the chance to apply her experience locating neurons that have discharges typical of those in the basal ganglia. In the operating room, Anderson trained staff to record discharges from neurons in a part of the basal ganglia called the global pallidius, and to interpret firing patterns. From this data, the surgeon localized the corrective surgery or found the place to implant the stimulator. Anderson surmised that the treatments worked by interrupting nerve cell misfiring, instead of by just changing their level of activity.

Advances had also taken place that further encouraged Anderson's laboratory work. Other clinicians and researchers found that MPTP, a contaminant in some street drugs, was behind the sudden, severe onset of Parkinson's-like symptoms in young drug users. MPTP causes the degeneration of dopamine- containing neurons. Also, epidemiologists noted that the incidence of Parkinson's was higher in farm areas where pesticides were used. They suggested that a susceptibility to toxins might be one mechanism that produces Parkinson's.

"After exposure to the garden and aquatic pesticide, rotenone, there's evidence in animal models that dopamine terminals degenerate in parts of the basal ganglia," Anderson said.

Parkinson's disease has a gradual course. Brain cell damage takes place over many years without causing alarm. A person appears fine until neural degeneration accumulates. Symptoms usually first appear in the fifth or sixth decade of life.

Parkinson's is characterized by rigid muscles and such tremors as pill rolling or nodding. People with the disorder tend not to swing their arms when they walk. Other previously automatic acts, such as buttoning a shirt collar without looking, require them to concentrate on what they're doing. An unanswered question, Anderson noted, is how the normal brain makes some movements automatic, and how this mechanism may be damaged in Parkinson's.

Other researchers, Anderson said, have shown that dopamine neurons are associated with reward and prediction of success. Dopamine is released by neurons in association with a successful action. It solidifies certain neural pathways. In other words, it acts on the brain activities that led to success and may cement certain habits. In addition to Parkinson's, in which movement is stymied, dopamine system irregularities are thought by some scientists to be why a few people are in almost constant motion from hyperactivity, Tourrette syndrome, or obsessive/compulsive disorder, in which a person carries out highly automatic behaviors.

What is poetry in motion but aligned posture, accurate aim, graceful movements, controlled strength and speed, and a return to a standstill without shaking or stumbling? Anderson has illuminated some components of the complex networks in the brain that modify movement second-by-second and that influence kinematics -- the scale, magnitude, amplitude, and velocity of motion. In tandem with the basal ganglia, the cerebellum helps run the action. The motor cortex coordinates signals from both structures through a relay center, the thalamus. The cerebellum excites, and the basal ganglia inhibits. Accurate signals from both result in physical coordination. An upset in either will cause a movement disorder.

Anderson has examined the zones excited or inhibited in the thalamus by the cerebellum and the basal ganglia and also has studied how output from the basal ganglia interacts at the thalamus with other sources of information, such as signals from the cerebral cortex. Poorly orchestrated signals may be the static that produces Parkinson's tremors. Anderson has also studied how neuron firing in the global pallidius relates to the kinematics of reaching, and how discharges change with different arm positions. For some studies, her team taught animals to play video games. (She wryly observed that they sometimes wanted to play by their own rules, not hers, and that their accuracy could exceed that of humans.)

While much has been learned, scientists are not yet able to determine what gives a person the motor skills of a talented pianist, dancer, painter, or sports figure, or a primate the agility to swing through the trees. What motor control research has contributed to is a greater understanding of the movement disorders that affect many people, to improved treatments, and to ideas for futuristic, brain-controlled, robotic tools for those paralyzed by stroke or trauma.

As a teacher, Anderson helps research trainees bridge the basic sciences and medicine. Her lab has hosted medical students, physicians, physical therapists, occupational therapists, and other clinicians who want to conduct neuroscience research, in addition to graduate students in neuroscience and in physiology and biophysics.

"One of my important duties," Anderson said, "is taking trainees from a clinical background and giving them research experience, in the belief that they might form a functional link between scientific discovery and clinical medicine."

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