Poster A17, Tuesday, August 20, 2019, 10:15 am – 12:00 pm, Restaurant Hall
gnikaepS sdrawkcaB: from extreme language traits to mechanisms
Hayley Mountford1, Stefan Prekovic2, Nayeli Gonzalez-Gomez1, Isabel Bermudez-Diaz1, Dianne Newbury1;1Oxford Brookes University, 2Netherlands Cancer Institute
Language ability is highly heritable and therefore has a strong genetic component. Despite decades of study, we understand little of the genetic and molecular mechanisms which underpin typical language development. Insights into the genetic basis of language have primarily come from the study of language disorders, implicating over thirty-five genes in language function. A key assumption being that the genes and mechanisms contributing to language disorders are the same factors that underpin typical language development. An alternative approach is offered through the neurological and genetic characterisation of individuals with extreme ability, rather than disability. We leverage this approach to better understand mechanisms relevant to typical language development. Here we report on a novel molecular mechanism identified through the investigation of an extreme language trait – the ability to speak backwards. We identified a father and daughter who can rapidly and accurately reverse phonemes to speak backwards fluently. We showed that this remarkable phenotype is underpinned by exceptional working memory. Using fMRI, we established that their extreme ability is supported by visual semantic loops within the left fusiform gyrus. Our analysis of this family identified a novel coding variant (c.G262A, p.G88R) in the gene RIC3; a chaperone of the α7 subunit of the nicotinic acetylcholine receptor (nAChR) which is critical for cholinergic synaptic transmission. The α7 nAChR is one of the most abundant receptors in the mammalian brain and plays a pivotal role in brain development. Traditionally, these receptors are associated with neuropsychiatric disorders such as schizophrenia and Alzheimer’s disease. Through electrophysiological studies using Xenopus laevis oocytes as a model for nAChR activity, we detected a positive functional effect of the RIC3 variant upon cholinergic synaptic transmission. This provides direct evidence for the role of RIC3 as a nAChR chaperone, and of its mediatory role in memory-related circuits. Expanding on these findings, we are currently recruiting and testing additional participants with the ability to speak backwards. Preliminary assessment suggests that this trait is heterogeneous, and not necessarily driven by superior working memory in all cases. This indicates that backwards speech is a complex trait with many neurological and genetic drivers likely to play a role. The successful identification of RIC3 and the characterisation of its role in working memory demonstrates the utility of extreme traits to uncover novel mechanisms that underpin language. By expanding this successful approach to a wider cohort of backwards speakers, we aim to characterise the cognitive processes that underpin backwards speech and use this to reveal novel neuromolecular pathways involved in language acquisition.
Themes: Language Genetics, Phonology and Phonological Working Memory
Method: Other