CLEVELAND -- When it comes to understanding human motor systems, the "eyes" have it.

The depth of knowledge related to the ocular motor system is immense, ranging from molecular genetics to abnormal behavior due to neurological disease. Eye movements can serve as a model of how the brain controls movement, and scientists study them to gain insight into diseases such as strabismus (lazy eyes), multiple sclerosis, Parkinson's disease, schizophrenia, migraines, and vertigo (dizziness).

Recent research into these diseases and the latest discoveries in how the brain and peripheral motor system generate eye movements are the focus of a conference at Case Western Reserve University, "Neurobiology of Eye Movements: From Molecules to Behavior," being sponsored by the New York Academy of Sciences. Bringing together scientists and physicians from four continents, the conference will be held in Ford Auditorium at CWRU's Allen Memorial Library.

Among the topics conference participants will be considering are brainstem and cerebellar mechanisms for controlling gaze, cerebral and basal ganglionic influences on gaze control, binocular aspects of gaze control, and vertigo and nystagmus and other disorders that disrupt clear vision.

Certain Advantages

"In general, cellular biologists don't talk much to systems physiologists, even though they may both be studying the brain," says CWRU's R. John Leigh, one of the organizers of the conference. "It's either the brain one molecule at a time or the brain as a computer."

Leigh says eye movements are a "refreshing exception" to this general attitude since it is really possible to look at the ocular motor system from the molecular level right up to complex behaviors. The reason is because eye movements offer certain advantages over other motor systems.

The eye has only three degrees of rotational freedom and all can be measured with precision. There is a fairly linear relationship between rotations of the eyes and the activity of motoneurons that cause the eye muscles to contract.

"It is possible to identify certain specific classes of eye movements, each of which has evolved for a certain purpose and has properties suited to that purpose," he says. "Furthermore, it is possible to identify distinct neural circuits dedicated to each type of eye movement, with the signals from each class summing at the motoneurons."

Leigh admits this is a simplified explanation, as recent work casts some doubt on just about every one of these "principles." But he notes that the ability to find these deviations from the simple rules has also led to advances. For example, it has been discovered that there are two layers to each extraocular muscle, and that the outer layer is attached to a pulley (not the eye). The inner layer of muscle runs through the pulley to attach to the eye.

"So we now have to look for two separate classes of motoneurons and figure out how they are coordinated," he says.

He adds that the frontal eye field in the cerebral cortex used to be viewed as responsible for generating rapid voluntary gaze shifts, known as "saccades," but now it turns out that at least three types of eye movement are encoded here. Thus, the frontal eye field may coordinate three different types of eye movements, each concerned with shifting our line of sight.

Advances in Understanding

"Congenital nystagmus and other acquired eye movement abnormalities lead to the eyes constantly moving, making the world appear to shake for a patient," says Henry J. Kaminski, conference co-organizer from Case Western. "Likewise, vertigo is an awful sensation that makes a sufferer feel like the world is spinning."

Kaminski notes, however, that progress in treating these disorders is being made. There is a new surgical procedure for nystagmus and even some non-surgical methods (including drug treatments and optical devices) that are promising. There are also advances in treatment for the common symptoms of vertigo, and surgeries being tested to treat stabismus.

Other researchers are studying the genetic mechanisms underlying relatively rare familial episodic ataxia and are gaining a better understanding of the more common vertigo and ataxia syndromes particularly associated with migraine. Migraine affects as many as 15-20 percent of the general population and it has been estimated that about a quarter of patients with migraine experience spontaneous attacks of vertigo and ataxia.

"John Leigh and I demonstrated that even when children with Duchenne muscular dystrophy are essentially paralyzed, their eyes move normally," says Kaminski. John Porter of the Research Institute of the University Hospitals of Cleveland has extended their studies in order to understand why eye muscles are spared by Duchenne muscular dystrophy, and he is gaining insight into the basic pathogenesis of muscular dystrophy.

"The eye muscles are unique and may hold the answer for a cure of muscular dystrophy," says Kaminski.

The conference is only the sixth in the past 20 years of similar significance. And why Cleveland? Robert B. Daroff, who the conference honors, pioneered the study of eye movements in Cleveland during his time as chair of the Department of Neurology at CWRU. He built a research team at University Hospitals of Cleveland and the Louis Stokes Veterans Affairs Medical Center that make it one of the world's premiere centers in the study of eye movements.

Proceedings of the conference will be published as a volume of the Annals of the New York Academy of Sciences.

Founded in 1817, the New York Academy of Sciences is an independent, non-profit organization of more than 25,000 members committed to advancing science, technology and society worldwide.