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An orderly test for brain disorders

September 25, 2008


Apostolos Georgopoulos.

Apostolos Georgopoulos, Regents Professor of neuroscience and neurology, has found patterns in the brain's magnetic signals associated with several brain disorders.

Photo: Patrick O'Leary

Spotting abnormal mental functioning in the magnetic activity of the brain

By Deane Morrison

People with brain disorders like schizophrenia, Alzheimer’s disease, or multiple sclerosis may not be able to tell a doctor what’s bothering them. But now their brain cells can, thanks to some ingenious detective work by University researcher Apostolos Georgopoulos.

Using a technique called magnetoencephalography (MEG), Georgopoulos and his research team were able to find patterns of magnetic activity in the brain’s cerebral cortex that reliably signalled the presence of those three disorders, plus chronic alcoholism, Sjögren’s syndrome, facial pain, and normal brain function.

The technique is the first to measure how the brain functions in real time. It may lead to a noninvasive test that could spot trouble in the early stages of a disease or monitor progress as patients undergo treatment. Already, Georgopoulos has found that the brain patterns of people with chronic alcoholism tend to revert toward normal as they abstain from alcohol.

"I did not expect to find this," says Georgopoulos, Regents Professor of Neuroscience and Neurology. "It’s like a silent movie of the brain." Georgopoulos also directs the Brain Sciences Center at the Minneapolis Veterans Affairs Medical Center, where he holds the American Legion Brain Sciences Chair.

The advantage of MEG is its ability to detect brain activity on a scale of milliseconds. In contrast, MRI scans are like snapshots with about a three-second exposure—much too long to detect the rapid "crosstalk" of brain cells in a meaningful manner. And EEG signals are delayed and distorted by passing through soft tissues and the skull, resulting in imprecise or unreliable readings, Georgopoulos says.

In their MEG studies, the researchers placed an apparatus resembling a helmet over the heads of the subjects, who were asked to follow a point of light with their eyes for 45 to 60 seconds. Inside the helmet were 248 sensors, each of which detected the magnetic fields generated in a population consisting of tens of thousands of cortical cells. Together, the sensors scanned the magnetic activity over the whole cortex.

The researchers then used sophisticated statistics to zero in on a few interactions between cell populations that varied according to different brain conditions. From the different patterns of interactions in 142 subjects tested, they were able to identify with 100 percent accuracy which of the six brain disorders a subject had been diagnosed with or if the subject had normal brain function.

"[This work] came out of my strong belief that the real function of the brain is in the interaction of its elements—that is, in the crosstalk," says Georgopoulos. "Exchange of information is the essence of brain function, which is defined as all interactions among all populations of cells.

"The dynamic function of the brain has been my obsession for years. For me, the biggest challenge is to find how the brain works on the millisecond level with all the ‘buzzing’ going on."

The emphasis on populations of cells is no accident. For many years, neuroscientists have recorded the activities of single neurons. But our brains are more like a vast array of neural choruses, each consisting of many neurons that sing together and respond to other choruses. Or, on a more prosaic note, one might say that the work of the brain is done by committee.

See how it works
See animation for a visualization (opens new window) of how the test works, patterns seen in Alzheimer’s disease and mild cognitive impairment, and how an alcoholic's brain changes as he abstains from alcohol.

Georgopoulos and his colleagues are now beginning long-term studies to see if they can predict the onset of Alzheimer’s disease. They are also expanding their studies to include depression, fetal alcohol syndrome, gambling, and mild cognitive impairment of various kinds. And they’ve started taking data on a wide swath of healthy volunteers between the ages of 8 and 100.

"He is a huge asset to the University, not only because of how smart he is but because of how collaborative he is," says S. Charles Schulz, head of the psychiatry department. 

In addition to his MEG work, Georgopoulos, in collaboration with Schulz, is studying brain disorders by means of MRI and neuropsychological data, which is taken from pencil and paper or computer tests of traits like attention, memory, and decision-making.

"In a preliminary study, we could differentiate young people with schizophrenia or bipolar disorder from controls," says Schulz. "That is important in the early stages because clinical [signs] are not really clear." The two resesarchers are now working to test statistical techniques to see if they can determine, when a schizophrenia patient first visits, what the early response to medication will be, so treatment can be better tailored to the person.

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