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H. HOUSTON MERRITT LECTURER
DAVID ZEE, MD
ON CIRCUITS IN THE BRAIN

He can't remember what channel it appeared on or how many episodes he saw. But neurologist David Zee, MD, Director of the Vestibular/Eye Movement Testing Laboratory at Johns Hopkins University, credits much of his early interest in science and medicine to a television special that he saw as a boy in the 1950s. The subject? Of all things, Johns Hopkins Hospital.

Whether it is in front of his television at a certain time on a certain channel during his childhood or at a lecture given by a forward-thinking bioengineer during his residency, Dr. Zee thinks his career owes much to being at the right place at the right time – with the right people.

As a medical student at Hopkins, Dr. Zee vacillated between two fields: pediatrics and neurology. Between his third and fourth years, a summer elective in neurology at the Mayo Clinic – which had no medical school of its own then, and was, at the time, one of the few schools to pay medical students for working as clinical clerks – turned him firmly in the direction of neurology.

As luck would have it, Hopkins was one of the few schools where neurology was a section in the department of medicine, not a separate department. That changed in 1969, when Guy McKhann became chairman of a new department of neurology and Hopkins launched its first neurology residency program.

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Dr. David Zee

Dr. Zee became part of the first cohort of neurology residents at the Johns Hopkins Hospital. “Everybody was enthusiastic about the department. The chairman would be down there in the middle of the night helping with lumbar punctures. It was like being on the ground floor in a great enterprise,” Dr. Zee recalled.

Meanwhile, as part of that first year of residency, first-year resident Dr. Zee joined a senior medical student, Neil Miller, at a satellite hospital for a neurology rotation.

“He'd already gone to San Francisco and Miami to do electives in the field, which I'd become interested in during my rotation at Mayo. Now, of course, Neil is probably the preeminent neuro-ophthalmologist in the country,” Dr. Zee said. “It was a good example of the student sparking the interest of the resident.”

With no MRI or CT scans to rely on, patient examinations formed a much larger proportion of the diagnostic arsenal. “Neuro-ophthalmology really lends itself to that. There is an anatomical basis for the signs in ophthalmologic problems – if you have trouble moving the eye, that indicates specific problems on the left or right side of the brain. It was a sophisticated diagnostic process, yet firmly entrenched in basic anatomy,” Dr. Zee said.

SYSTEMS NEUROSCIENCE

With this burgeoning interest in neuro-ophthalmology, Dr. Zee was primed and ready when the last piece of his career puzzle fell into place at a lecture delivered by Hopkins bioengineer and physiologist David Robinson.

“A single lecture can really turn your life around,” Dr. Zee marveled. “He talked about mathematical models of how information is processed in the brain – the beginning of systems neuroscience. I said ‘That's it! That's what I want to do!’” So Dr. Zee invested his substantial third-year elective time in learning the principles of control systems with Robinson, and decided to focus his attention on eye movement problems.

“It's all about the bench to the bedside, and vice versa,” Dr. Zee said of his eye movement studies. “We can look at a patient who has a problem and, by understanding how information is processed in the normal brain, we can look at a clinical problem – use the way in which the system ‘falls apart,’ so to speak, to infer something about how the brain works.”

BRAIN RESPONSE TO LESIONS

A major focus of Dr. Zee's laboratory involves how the brain adapts to lesions, whether they are caused by stroke, trauma, or something else. “We've been trying to unravel the mechanisms, at a behavioral level, of ocular motor learning, so the brain can pick things up when they go wrong,” he said.

“If I give you a funny pair of glasses and you wear them for a few hours, you can adapt to them. That is an example of a normal person adapting to new circumstances. With monkey models, we've been trying to figure out which parts of the brain mediate this adaptation.” Outside the lab, such improved understanding might help design the most effective physical therapy programs.

Another area of brain function that fascinates Dr. Zee is how it operates to make two eyes work together for stereoscopic vision, creating what the person perceives as a single object. “We've become very interested in disorders such as strabismus and the ophthalmologic problems of impaired binocular vision,” he said. “One way to fix eye misalignment is to operate, of course; but another is to design better ways of using prisms and let the brain do the repair, rather than the surgeon.”

One particularly thorny problem is superior oblique muscle palsy. “It is a difficult condition. Many patients have to be operated on two or three times, even by the best surgeons,” he said. “But the evidence suggests that by carefully analyzing eye movements, we can suggest what kind of surgery should be undertaken. If we give the surgeons a better idea of what to do, that is much better for the patients and offers them visual comfort more quickly.”

PLENARY TOPIC

During the Annual Meeting's plenary session in the inaugural H. Houston Merritt Lecture on “Single Case Reports: Windows to Brain Function,” Dr. Zee plans to describe some of these cases.

“Our analytical approach is based on signal processing, so an engineering parlance and approach are perfect for this. Engineers think in circuits, and we are hypothesizing circuits in the brain, then thinking about what might go wrong in your particular circuit and what that abnormality might mean,” Dr. Zee said.

“Even as a clinician in practice, if we remember our physiology and anatomy and remain inquisitive, we can learn a lot just from examining one patient who has a peculiar or unusual problem. That's what I'm going to talk about.”