October 26, 1999

New Way of Looking at Diseases of the Brain

A highly respected neuroscientist has developed a provocative new theory of how the brain is organized which, if confirmed, would explain how and why the mind produces symptoms found in several seemingly unrelated disorders.

According to the theory, the deep sadness in severe depression, the hand wringing in obsessive compulsive disorder, the ringing in the ears of tinnitus, the unrelenting discomfort of chronic pain and the shaking and immobility seen Parkinson's disease all stem from the same basic brain defect: a decoupling of two brain regions that normally fire their cells in synchrony.

If the theory is correct, it would explain why experimental surgical techniques involving implanting electrodes in the brain to treat Parkinson's disease and depression seem to work so well, and it would expand their application to other brain diseases.

The neuroscientist, Dr. Rodolfo Llinas, a professor at New York University Medical School, presented his findings on Sunday night in Miami to some 4,000 researchers attending the annual Society for Neuroscience meeting.

Although the theory has not yet been subjected to peer review, a paper describing the work was submitted last week to Proceedings of the National Academy of Sciences and accepted for publication in just two days.

Dr. Llinas is a member of the academy, which often publishes the work of leading scientists or their protégés when the ideas are new and have not yet been tested by others.

"This work is very important," said Dr. Edward Jones, president of the Society for Neuroscience and director of the Center for Neuroscience at the University of California in Davis.

"What makes it so compelling is that it doesn't come completely out of left field.

It builds on a body of work that's been growing for some time.

Everyone will say wow, yes!"

Because these new insights into brain organization, if confirmed, would almost certainly promote the use of surgery to treat psychiatric and neurological diseases, other scientists urged caution in applying the theory. They are concerned because psychosurgeries that were tried 30 to 40 years ago in these same regions of the brain made many people mentally incompetent.

The theory involves two brain areas -- the cerebral cortex and the thalamus -- and how they communicate.

The cortex is a thickly folded band of tissue that carries out higher mental capacities in humans and other mammals. It is composed of six layers of cells that are highly interconnected and organized into specialized regions that allow people to move their bodies, plan for the future, talk, listen, sense touch, respond to emotions and carry out other functions. The sixth layer of these cells is also directly connected through nerve fibers to cells in the thalamus, an older brain structure that is just under the cortex.

The thalamus is usually thought of as a relay station. Virtually all information flowing from the outside world and lower brain regions must go through the thalamus before being passed on to the cortex.

But according to Dr. Llinas, the thalamus does much more than simply pass information.

The way that it coordinates its activity with the cortex, he says, gives rise not only to the symptoms seen in many neurological and psychiatric diseases, but to consciousness itself.

It does so through what Dr. Llinas calls thalamo-cortical oscillations. The thalamus contains special cells that pass tiny electrical currents across their membranes in a highly coordinated manner, Dr. Llinas said in a telephone interview. Rather than firing sporadically and singly, like other nerve cells, the cells in the thalamus oscillate, firing in groups together at various frequencies.

By virtue of their connections, these thalamic cells then cause cells in layer six -- the layer of the cortex closest to them -- to oscillate at the same frequency. This coordination between these oscillating cells in the cortex and thalamus, which are constantly flipping signals back and forth, binds information from different regions of the brain into complete actions, perceptions, movements and into consciousness itself, he said.

When the cells oscillate at a high frequency, the brain is awake and alert.

When they fall into low frequencies, the brain becomes disconnected, unconscious and falls asleep.

In studying patients with various brain diseases, Dr. Llinas and his colleagues noticed that particular regions of their thalamuses oscillated at abnormally low frequencies, as if those regions were asleep.

When this happens, Dr. Llinas said, key parts of the cortex are decoupled from the thalamus. Those parts of the cortex then become overly excited because they are no longer under proper control, he said, and symptoms of dysfunction emerge.

For example, a defect in one tiny part of the thalamus that projects to one of the higher areas controlling movements can cause those movements to become uncoordinated.

The result is the tremors seen in Parkinson's disease.

If the defect is a fraction of an inch away, a different part of the region controlling movement is affected, resulting in the rigidity seen in many patients.

Chronic-pain sufferers also have sluggish regions of the thalamus, Dr. Llinas said.

Areas of the cortex that deal with pain become overexcited, producing intense discomfort that does not respond to drugs.

Dr. Llinas speculates that the same underlying defect causes some types of depression, most tinnitus and obsessive compulsive disease. In each case, according to his theory, a part of the thalamus is out of phase with the cortex which, unregulated, produces symptoms of profound sadness, ringing in the ears or endless hand washing.

All these disorders might be treated by implanting electrodes into the thalamus to break the abnormal oscillation patterns, Dr. Llinas said. In fact, the most effective treatment for Parkinson's patients who do not respond to drug therapy involves putting electrodes directly into the thalamus.

"This breaks the abnormal disconnection and the person immediately gets better," Dr. Llinas said. "But you have to keep the electrode in. It's like a pacemaker." Similar surgeries have been tried successfully for chronic pain and depression. In each case, the electrode is targeted on only a few thousand cells.

By SANDRA BLAKESLEE
Copyright 1999 The New York Times Company
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