Visual motion processing deficits in infants with the fragile X premutation

Abstract

BackgroundFragile X syndrome (FXS) results from a trinucleotide repeat expansion (full mutation >200 cytosine-guanine-guanine (CGG) repeats) in the FMR1 gene, leading to a reduction or absence of the gene’s protein product, fragile X mental retardation protein (FMRP), ultimately causing cognitive and behavioral impairments that are characteristic of the syndrome. In our previous work with infants and toddlers with FXS, we have been able to describe much about their cognitive and visual processing abilities. In light of recent work on the mild cognitive deficits and functional and structural brain differences that are present in adults with the fragile X (FX) premutation, in the present study we examined whether some of the low-level visual processing deficits we have observed in infants with FXS would also be present in infants with the FX premutation (55–200 CGG repeats).MethodsWe chose a contrast detection task using second-order motion stimuli on which infants with FXS previously showed significantly increased detection thresholds (Vision Res 48:1471–1478, 2008). Critically, we also included a developmental delay comparison group of infants with Down syndrome (DS), who were matched to infants with FXS on both chronological and mental age, to speak to the question of whether this second-order motion processing deficit is a FX-specific phenomenon.ResultsAs reported previously, infants with the FX full mutation showed motion contrast detection threshold levels that were significantly higher than age-matched typically developing control infants. Strikingly, the motion detection contrast levels of FX premutation infants were also significantly higher than typically developing (TD) infants and not significantly different from the group of infants with FXS or with DS.ConclusionsThese results, which are in keeping with a growing body of evidence on the mild cognitive and perceptual processing deficits and functional and structural brain differences that are present in adults and older children with the FX premutation, underscore the pressing need to study and describe the processing capabilities of infants and toddlers with the FX premutation.

Abnormal trajectories in cerebellum and brainstem volumes in carriers of the fragile X premutation

“…It generates internal models for behaviors, and guides the neocortex to store the most efficient representations for movement and high level cognitive and emotional processing (Koziol et al , 2012). Subtle under-development of the cerebellum may underlie developmental problems, including autism, anxiety and deficits in attention and visual motion processing that have been documented in children with fragile X premutation (Farzin et al , 2006, Gallego et al , 2014, Cordeiro et al , 2015) as well as motor impairment in FXPC− (O’Keefe et al , 2015). In FXTAS cerebellar structural damage becomes clinically observable, with MRI signal hyperintensities in the MCP being used as a diagnostic criterion (Brunberg et al , 2002).…”

A Randomized, Double-Blind, Placebo-Controlled Trial of Low-Dose Sertraline in Young Children With Fragile X Syndrome

“…Although sertraline did not produce significant language gains over placebo, it is interesting and encouraging for the families that the visual perceptual and fine motor skills of children with FXS were significantly improved by sertraline because these are common deficits seen in FXS. Visual perceptual problems, specifically reduced contrast sensitivity to second order movement, can be detected in the first year of life in eye-tracking studies of babies with FXS 13,14 . Subsequent visual perceptual problems including visual memory, visual spatial perception, and visual motor coordination are problematic in both males and females with FXS 54–57 .…”

“…FXS is characterized by significant behavioral, cognitive, and emotional dysregulation including symptoms of anxiety, ASD, attention deficit hyperactivity disorder (ADHD), self-injurious behavior, irritability, aggression, impulsiveness, sensory processing vulnerabilities, and language deficits 5–11 . In addition, there are motor coordination deficits 11,12 and visual perceptual deficits; the latter of which have been documented even in infancy with eye tracking studies 13,14 . FXS is also highly associated with ASD; approximately 60% of patients with FXS also have ASD 7,15,16 .…”

Developmental profiles of infants with an FMR1 premutation

“…This study examined 14 infants with the premutation and found visual processing deficits similar to infants with FXS, although their overall developmental scores were higher than those with FXS [36]. The findings suggested that deficits in spatiotemporal processing and subsequent executive dysfunction in some adults with the premutation may be present very early in life and emphasize the importance of studies examining early development of individuals along the spectrum of FMR1 mutations.…”