Language processing skills linked to FMR1 variation: A study of gaze-language coordination during rapid automatized naming among women with the FMR1 premutation

Abstract

The FMR1 premutation (PM) is relatively common in the general population. Evidence suggests that PM carriers may exhibit subtle differences in specific cognitive and language abilities. This study examined potential mechanisms underlying such differences through the study of gaze and language coordination during a language processing task (rapid automatized naming; RAN) among female carriers of the FMR1 PM. RAN taps a complex set of underlying neuropsychological mechanisms, with breakdowns implicating processing disruptions in fundamental skills that support higher order language and executive functions, making RAN (and analysis of gaze/language coordination during RAN) a potentially powerful paradigm for revealing the phenotypic expression of the FMR1 PM. Forty-eight PM carriers and 56 controls completed RAN on an eye tracker, where they serially named arrays of numbers, letters, colors, and objects. Findings revealed a pattern of inefficient language processing in the PM group, including a greater number of eye fixations (namely, visual regressions) and reduced eye-voice span (i.e., the eyes’ lead over the voice) relative to controls. Differences were driven by performance in the latter half of the RAN arrays, when working memory and processing load are the greatest, implicating executive skills. RAN deficits were associated with broader social-communicative difficulties among PM carriers, and with FMR1 -related molecular genetic variation (higher CGG repeat length, lower activation ratio, and increased levels of the fragile X mental retardation protein; FMRP). Findings contribute to an understanding of the neurocognitive profile of PM carriers and indicate specific gene-behavior associations that implicate the role of the FMR1 gene in language-related processes.

Understanding Social-Communication Differences in Autism Spectrum Disorder and First-Degree Relatives

“…For example, Mosconi et al (2010) found that firstdegree relatives of individuals with ASD demonstrated ocular-motor differences such as minor inaccuracies in direction of eye movement and subtly reduced inhibition of eye movements. Differences in eye-voice coordination have also been observed in ASD and among parents in nonsocial, rapid automatized naming tasks requiring fluid scanning and naming of colors, objects, letters, and numbers (Nayar et al 2018). Of note, similar differences in eye-voice coordination have been noted in carriers of the FMR1 premutation (Nayar et al 2019).…”

“…Differences in eye-voice coordination have also been observed in ASD and among parents in nonsocial, rapid automatized naming tasks requiring fluid scanning and naming of colors, objects, letters, and numbers (Nayar et al 2018). Of note, similar differences in eye-voice coordination have been noted in carriers of the FMR1 premutation (Nayar et al 2019). Full mutations of the FMR1 gene cause fragile X syndrome, the most common inherited cause of intellectual disability and also the monogenic disorder most frequently associated with ASD (e.g., Zafeiriou et al 2013).…”

“…For instance, parents with the BAP have been shown to exhibit subtle differences in social cognition, including differences in reading emotional states from faces, biological motion, and complex emotional scenes (Adolphs et al 2008;Losh and Piven 2007;Losh et al 2009). BAP-specific differences have also been observed in studies of language processing in ASD and first-degree relatives, where parents with the BAP showed reduced language automaticity and differences in eye-voice coordination (a measure of efficient language processing) during rapid automatized naming tasks (Losh et al 2010;Nayar et al 2018). Together, these finding suggest that specific language and social phenotypes could reflect genetic liability to ASD and be useful in identifying subgroups of families who may be more similar in underlying etiologic factors.…”

Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS): Pathophysiology and Clinical Implications

“…Moreover, compared to mothers of children with ASD who were considered to have similar parental experiences to the PM mothers of children with FXS, the latter group had higher scores in verbal dysfluency and impaired self-monitoring [ 92 ]. Furthermore, in a study by Nayar and colleagues, they examined language processing skills in 46 females with the PM and 56 controls and they found a pattern of inefficient language processing among the females with the PM [ 93 ]. In individuals with FXTAS, it is necessary to address cognitive impairment and implement early intervention since impaired information processing speed, response inhibition, and working memory could interfere with their mobility [ 94 ].…”

A Unique Visual Attention Profile Associated With the FMR1 Premutation

“…Differences in executive skills have also been reported, including working memory, inhibitory control, and processing speed ( Wang et al, 2013 ; Shelton et al, 2014 , 2015 , 2016 ). Subclinical phenotypic differences have also been documented in social cognition ( Cornish et al, 2005 ; Losh et al, 2008 ), language processing ( Nayar et al, 2019 ), and social language use ( Losh et al, 2012 ; Klusek et al, 2016 ) in women with the PM. Manifestation of the PM phenotype is thought to be in part related to molecular-genetic differences including levels of FMRP and CGG repeat length ( Wheeler et al, 2014 ).…”