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Autism AutismAutism

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 passive role is 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.

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.

The researchers understand that some important brain responses are too small or missing in autism, and a new framework of analysis may help them to understand why. Using the band metaphor, Salk scientists believe that 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.

Recent Discoveries

  • Recent Discoveries Salk researchers were able to obtain induced pluripotent stem (iPS) cells from patients' skin cells and to differentiate them into the cell type damaged by Rett syndrome, a genetic disease that causes developing infants to progressively lose speech and motor skills. They then used these cells to replicate autism in the lab and study the molecular pathogenesis of the disease. This allows them to start looking for new drugs based on measureable molecular defects.
  • Salk 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. 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. Salk scientists are now focused on the next big question: Can they find differences that account for autism and other brain disorders?

Nicola J. Allen
Assistant Professor
Molecular Neurobiology Laboratory
Hearst Foundation Development Chair

Kenta Asahina
Assistant Professor
Molecular Neurobiology Laboratory

Ursula Bellugi
Professor and Director
Laboratory for Cognitive Neuroscience
Salk Founders' Chair

Rusty Gage
Laboratory of Genetics
Vi and John Adler Chair for Research on Age-Related Neurodegenerative Disease

Saket Navlakha
Assistant Professor
Integrative Biology Laboratory

Dennis D. M. O'Leary
Molecular Neurobiology Laboratory
Vincent J. Coates Chair in Molecular Neurobiology

Terrence J. Sejnowski
Professor and Laboratory Head
Computational Neurobiology Laboratory
Howard Hughes Medical Institute Investigator
Francis Crick Chair

Unlocking the Mystery of Autism

The pictures of her first birthday party show a smiling little girl, excitedly reaching for the candles on her cake. A year later, she is unable to sit up or grasp with her fingers. Rett syndrome, a devastating brain disorder, has thrown her development into reverse.

Autism Triggered by a tiny genetic flaw, the rare disease afflicts girls almost exclusively. The symptoms start to emerge just as they are beginning to walk and talk. Seemingly out of the blue, normal development slows down, and eventually the infants regress, progressively losing speech and motor skills. Toddlers who used to bask in their parents' attention often become withdrawn and anxious and avoid eye contact. Instead of reaching for toys, they wring their hands over and over again, leading researchers to classify Rett syndrome as one of the autism spectrum disorders. But unlike most forms of autism, which have no single known cause, almost all cases of Rett syndrome can be traced to defects in a single gene known as MeCP2.

"Because of similar symptoms and shared genetic links, Rett syndrome is sometimes considered a "Rosetta Stone" that can help us to understand other developmental neurological disorders such as autism and schizophrenia," says Fred H. Gage, a professor in the Salk's Laboratory of Genetics and holder of the Vi and John Adler Chair for Research on Age-Related Neurodegenerative Diseases.

Read more in InsideSalk»

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