Scientists have proposed a provocative new theory that may help explain brain ailments as diverse as Parkinson's disease and depression.
The uncontrollable body movements of Parkinson's, the psychic agony of depression, the maddening ringing in the ears of tinnitus and a host of other neurological and psychiatric ailments may all be caused by the electrical misfirings of two key parts of the brain, according to the theory.
"What we have discovered is a whole new syndrome," said Rodolfo Llinas of New York University School of Medicine, who outlined his theory last week at a meeting of the Society for Neuroscience in Miami.
The new theory could provide insight into why people with various brain problems appear to improve after undergoing certain types of brain surgery. It could also lead to new ways to treat such problems, including novel drugs, surgeries and even implanting the equivalent of pacemakers in the brain, he said.
"This could be very exciting," said Llinas, who also published evidence supporting his theory in last week's issue of the Proceedings of the National Academy of Sciences.
"This means that we are going to understand a whole lot of neurology and psychology that didn't make sense before," said Llinas, chairman of the department of physiology and neuroscience, in a telephone interview. "We may be able to design better drugs. Or perhaps through surgery. We now know the issue is to break that low frequency."
Other researchers, while saying more research is needed to confirm Llinas's theory, said the findings are provocative.
"I think it's a very important contribution, for a number of reasons," said Edward Jones, director of the center for neuroscience at the University of California at Davis and president of the Society for Neuroscience. "This is not something coming out of left field. It's building upon a very good basis of fundamental knowledge. It represents a synthesis and an interpretation that some of us hadn't really thought of before."
Llinas and his colleagues unveiled the theory after using a technique called magnetoencephalography (MEG) to study the electrical firings of the brains of nine healthy people and compare them with nine people suffering from brain problems as diverse as Parkinson's, depression, tinnitus and unexplained pain.
The people with brain problems showed a distinctive abnormal pattern of electrical activity that Llinas called "thalamo-cortical dysrhythmia" because it involves apparent misfirings in parts of the brain called the thalamus and the cerebral cortex.
The thalamus is a clump of cells deep inside the brain that serves as a kind of relay station for almost all the information coming into the brain. The cerebral cortex is the part of the brain involved in perception, thought and recognition of information.
Llinas had previously shown that when people are awake and alert, their thalamus and cortex fire in synchrony at a high frequency, creating consciousness. When people sleep, the firings are at a low frequency.
In the new research, Llinas and his colleagues found that parts of the thalamus in people with brain problems had electrical firings of unusually low frequency even though they were awake. It was as if parts of their brains were asleep.
"Something very clearly was happening. There was a complete change in the baseline frequency," he said.
The misfiring in the thalamus appears to cause part of the cortex to then misfire in a low frequency, which then causes other parts of the cortex to fire at a high frequency, Llinas said.
The result is that messages in the brain are scrambled, causing various symptoms. The precise result of that scrambling depends on exactly which part of the thalamus is misfiring, Llinas said.
For example, Parkinson's patients experience damage to another part of the brain, which appears to cause part of the thalamus to misfire, resulting in faulty messages to the cortex and the symptoms of the disease.
When the misfiring occurs in a slightly different part of the thalamus, it causes depression. And so on for myriad other neurological problems, perhaps including psychiatric illnesses such as schizophrenia and obsessive-compulsive disorder, Llinas said.
"The beautiful thing about the Llinas paper is that one kind of synchrony entrains another, and the principle behind the recent findings is that if somehow or other this entrainment gets out of whack, then you're going to get symptoms that manifest in many different states," Jones said. "If we can consider that these two things get jumbled up, depending on which part of the thalamus is out of kilter with the whole, then you get these different manifestations."
Llinas stressed that this would not necessarily be the case for every problem involving the brain, and that some other problem would still be the trigger that caused the misfiring.
Nevertheless, potentially drugs could be found to help correct the misfirings, alleviating the symptoms. Alternatively, electrodes could be implanted into the brain to help regulate electrical firings, just as pacemakers modulate electrical firings in the heart. There is even a possibility that the problem could be corrected surgically by removing the misfiring part of the thalamus, Llinas said.
Other researchers cautioned, however, that much more research would be needed to confirm the findings. And brain surgery for psychiatric problems has a long history of ethical problems.
"The field of psychosurgery is fraught over the years and is not one many of us want to get into again because of the social and ethical problems associated with it," Jones said. "On the other hand, there is now a potential mechanism here. People will start to think about whether this is a realistic possibility."
David McCormick, a professor of neurobiology at Yale University, agreed, saying that while the theory is interesting, at this point it is based on very preliminary data that needs to be followed up.
"This is an interesting hypothesis that should go on to be tested in animals with detailed recording techniques and in humans with a variety of techniques . . . before it's put into practice," McCormick said.
CAPTION: MEASURING MAGNETIC FIELDS (This graphic was not available)