Matching speech pattern in mice, humans offers clues about origin of stuttering

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Stuttering has mystified researchers for centuries, but a new mouse model that mimics speech patterns of humans who stutter has provided researchers with more insight on the disorder.

In a study published Thursday in the journal Current Biology, researchers at Washington University found that mice engineered to possess a genetic mutation linked with stuttering in humans had a specific speech pattern. When analyzing humans for that same pattern, researchers observed a correlation.

"Speech is obviously a unique human capacity, but the patterns of speech are built out of a lot of building blocks that are much simpler," senior study author Tim Holy, an associate neurosciences professor at Washington University, said in a news release. "You have to be able to control the timing of your breath, and the fine muscles in your tongue and mouth. You have to be able to initiate movement. Those kinds of things may be shared all the way from mice to people."

Study authors contrived an algorithm to examine the length of pauses in the spontaneous vocalizations in 3- to 8-day-old mouse pups. Young mice make these sounds constantly but at high pitches undetectable to the human ear.

Researchers found the mice with the stuttering-linked genetic mutation took longer pauses than those without that genetic difference. When applying their algorithm to people, some of who stuttered and some who didn’t, they found the algorithm matched the speech patterns of the stutterers. Study authors also found that the mice with the genetic mutation uttered syllables more consistently than those without the mutation— a pattern that matched the human group.

"We found abnormalities that mimic some features of human stuttering," Terra Barnes, a senior scientist in Holy’s lab, said in the release.

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When researchers studied the genetically altered mice for other differences that could be attributed to stuttering— like abnormalities in balance, strength, coordination, movement initiation, spatial learning, memory and sociability— they didn’t find any links with the speech disorder. That mice with and without the genetic mutation were the same biologically and behaviorally except for their speech differences matches the characteristics of humans with and without the mutation, researchers noted.

"One of the things we find scientifically interesting about stuttering is that it is so precisely limited to speech," Holy said. "It's a very clean defect in an incredibly complex task."

Although researchers aren’t sure how the gene plays a role in speech, it’s involved in the pathway that degrades molecules inside the cell.

"It's kind of crazy that this gene that's involved in digesting the garbage in your cells is somehow linked to something so specific as stuttering," Holy said in the release. "It could be that the protein has many functions and this mutation affects only one of them. Or the mutation could very mildly compromise the function of the protein, but there's a set of cells in the brain that is exquisitely sensitive, and if you ever so slightly compromise the function in those cells you get the observable behavioral deficit."

Next, researchers are using their mouse model to further explore the disorder.

"We're coming up with lots of studies we can do to figure this out," Barnes said.