Genetic FoxP2 Defect May Cause Speech Disorders Independent Of Learning Disabilities
New research involving songbirds may offer scientists great insights into how genetic mutations of the FoxP2 gene affect certain cognitive processes and not others.
A new study conducted by researchers at the Duke University School of Medicine (DUSM) shows that adult male zebra finches cannot properly direct their songs to females when experimenters introduced targeted sequences of RNA that suppress the FoxP2 gene expression. Despite having spent thousands of hours learning these songs as juveniles, the adult birds showed difficulty limiting their range of songs to those intended for females. This signaled to the researchers that, in humans, learning disabilities may function independently of the common speech disorders in people with the defect.
"Our results integrate a lot of different observations that have accrued on the FoxP2 mutation and cast a different perspective on what this mutation is doing," Dr. Richard Mooney, the George Barth Geller professor of neurobiology at DUSM, said in a statement. "FoxP2 mutations do not simply result in a cognitive or learning deficit, but also produce an ongoing motor deficit. Individuals with these mutations can still learn and can still improve; it is just harder for them to reliably hit the right mark."
This inability to “hit the right mark” was observed in the zebra finches that Mooney and his colleague, a former graduate student named Malavika Murugan, Ph.D, introduced to FoxP2 suppressions. The song birds, which normally attune their songs to specific sounds when courting females, were unable to reduce their song variability. In other words, they kept singing as if the female weren’t even there.
Realizing the effect of FoxP2 suppression, the team then sent an electrical signal through the basal ganglia of both suppressed FoxP2 birds and those who could still maintain their songs. They found that one of the key determinants of whether the signal passed through quickly was the brain’s sensitivity to dopamine.
Dopamine is a neurotransmitter responsible for, among other things, the reinforcement of learned behaviors such as singing or playing sports. The birds with suppressed FoxP2 genes also had insensitivities to dopamine, which normally should produce reward-seeking behaviors, but in the mutant subjects had no effect.
"So what we think is happening is knocking down FoxP2 makes the male incapable of reducing song variability in the presence of a female,” Murugan said. “An adult male sees the female, there is an influx of dopamine, but because the system is insensitive, the dopamine has no effect and the adult male continues to sing a variable tune.”
The most common speech disorder resulting from a FoxP2 gene mutation is known as developmental verbal dyspraxia (DVD). It arises primarily from the mutation’s impairment on motor control, as children with DVD have repeated trouble forming consonants and vowel sounds. They often elongate specific syllables, stressing some while clipping others short. This is often connected with impaired prosody, a feature of children with autism, where the affected child has stilted intonation and language rhythms.
These are the same rhythms the present researchers were seeking in zebra finches, whose FoxP2 genes were suppressed. And although the parallels aren’t totally inclusive, the researchers concede, understanding how birds process gene mutations through language can offer valuable insights for how children develop speech disorders relative to learning disabilities.
"Birds are one of the few non-human animals that learn to vocalize," said Mooney. "They produce songs for courtship that they culturally transmit from one generation to the next. Their brains might be a thousandth the size of ours, but in this one dimension, vocal learning, they are our equal."
Source: Murugan M, Harward S, Scharff C, et al. Diminished FoxP2 Levels Affect Dopaminergic Modulation of Corticostriatal Signaling Important to Song Variability. Neuron. 2013.