January 24, 2002

New View of Brain's Inner Workings Opens Research Into Autism, Other Disorders

Salk News

New View of Brain’s Inner Workings Opens Research Into Autism, Other Disorders

La Jolla, CA – According to accepted dogma, the brain responds to sensory experiences somewhat like an electronic bucket brigade, with incoming signals passed from one region to the next in a somewhat linear fashion.

This somewhat passive role is now being challenged by new studies led by neuroscientists and computational biologists at The Salk Institute. Instead of the bucket brigade metaphor, these scientists see the brain more as an improvisational jazz band adjusting its ongoing parts to the arrival of new voices or themes.

“Our data indicate the brain ‘at rest’ is more like a group of jazz musicians warming up – each instrument or brain area is playing a different tune,” said Terrence Sejnowski, professor of computational neuroscience at Salk and senior author of the study that appears in the current issue of the journal Science.

“Then, when a lead musician starts playing a new theme (i.e. stimulus), most of the other instruments adjust their rhythm,” says first author Scott Makeig, a senior staff scientist in Sejnowski’s laboratory and director of the Swartz Center for Computational Neuroscience at the University of California, San Diego.

The result suggests a far more dynamic view of the brain’s activity than is envisioned in standard analyses.

It also opens new avenues to explore certain brain dysfunctions including schizophrenia and autism.

“We know that some important brain responses are too small or missing in autism. This analysis may help us to understand why,” said Eric Courchesne, a professor with UCSD’s School of Medicine and one of the study’s authors.

“In terms of Terry’s metaphor, there’s a good possibility that in autism the coherence of the band is missing. There is no reorganization, and the instruments continue to play their own tunes, ” he added.

The report applies a new method of analysis to data from an experiment in visual perception.

In the experiments, 15 human subjects watched as colored circles flashed on a screen while EEGs, were recorded at 31 locations across their scalps. The dynamics of the before-stimulus brain waves were compared with the altered after-stimulus activity.

“Researchers have traditionally collected hundreds of similar trials from each subject in such experiments, and then averaged the results,” said Makeig.

In the new study, the investigators applied a recently developed mathematical technique called ICA (Independent Component Analysis) that allowed them to examine each of the more than 13,000 trials individually.

“Before the flash there were lots of wave-like activity, but phase varies randomly from trial to trial,” said Sejnowski. If you average many trials together, the peaks and troughs cancel one another out, resulting in a straight line.

“What appears to happen is that the stimulus resets the phase of these waves so that after the stimulus the peaks and troughs tend to occur at similar times from trial to trial. If you sum over many trials, you accentuate both the peaks and valleys, giving the appearance of a new, stronger EEG signal.”

Seven independent sources of brain waves were discovered that adjust their signals following a flashed stimulus. Each source represents synchronous neuronal activity in a brain area, something like a heart’s pacemaker. When the pacemaker stops functioning coherently and each heart cell chooses its own rhythm, fibrillation occurs.

The way doctors or paramedics get the heart beating again is to shock it, which resets the pacemakers to act in phase with one another. In the brain, a stimulus acts similarly, re-setting the phase of the oscillations and bringing them into synchrony, albeit briefly. Although most subjects showed evidence of several brain wave sources, they had individual differences with respect to strength, amplitude and frequency of the associated EEG waves.

“You would expect this, of course,” said Sejnowski. “One next question is: can we find differences that account for brain disorders such as schizophrenia or autism?”

The study called “Dynamic Brain Sources of Visual Evoked Responses,” was conducted in collaboration with Salk co-authors M.Westerfield, S. Enghoff and T-P. Jung; and UCSD co-author J.Townsend, Westerfield and Jung are members of the Swartz Center for Computational Neuroscience at UCSD, which Sejnowski and Makeig direct. Sejnowski is a Howard Hughes Medical Institute investigator and an adjunct professor at UCSD. The study was founded by the National Institutes of Health, the National Institute of Neurological Disorders and Stroke, the U.S. Office of Naval Research, the Fulbright Program and the Swartz Foundation.

The Salk Institute for Biological Studies, located in La Jolla, Calif. Is an independent non-profit institution dedicated to fundamental discoveries in the life sciences, the improvement of human health and conditions, and the training of future generations of researchers. The Institute was founded in 1960 by Jonas Salk, M.D., with a gift of land from the city of San Diego and the financial support of the March of Dimes Birth Defects Foundation.

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