Translating dyslexia across species

Abstract

Direct relationships between induced mutation in the DCDC2 candidate dyslexia susceptibility gene in mice and changes in behavioral measures of visual spatial learning have been reported. We were interested in determining whether performance on a visual-spatial learning and memory task could be translated across species (study 1) and whether children with reading impairment showed a similar impairment to animal models of the disorder (study 2). Study 1 included 37 participants who completed six trials of four different virtual Hebb-Williams maze configurations. A 2 × 4 × 6 mixed factorial repeated measures ANOVA indicated consistency in performance between humans and mice on these tasks, enabling us to translate across species. Study 2 included a total of 91 participants (age range = 8-13 years). Eighteen participants were identified with reading disorder by performance on the Woodcock-Johnson III Tests of Achievement. Participants completed six trials of five separate virtual Hebb-Williams maze configurations. A 2 × 5 × 6 mixed factorial ANCOVA (gender as covariate) indicated that individuals with reading impairment demonstrated impaired visuo-spatial performance on this task. Overall, results from this study suggest that we are able to translate behavioral deficits observed in genetic animal models of dyslexia to humans with reading impairment. Future studies will utilize the virtual environment to further explore the underlying basis for this impairment.

Utility of the Hebb–Williams Maze Paradigm for Translational Research in Fragile X Syndrome: A Direct Comparison of Mice and Humans

“… Shore et al (2001) report consistent efficiency and rate of learning for three mazes (6, 8, and 12), however, statistical results for these group comparisons are not provided. Gabel et al (2016) report consistent efficiency and rate of learning for all mazes tested (5, 6, 11, and 12). The discrepancy between our results and those obtained with typically developing participants underline the relevance of directly comparing affected humans and mice to evaluate the validity of translational paradigms in FXS.…”

“…Using FXS as a model disease, we examined the potential utility of the Hebb–Williams maze paradigm ( Hebb and Williams, 1946 ; Rabinovitch and Rosvold, 1951 ) for translational and drug discovery research on the basis of three validation criteria. The paradigm allows direct comparison of humans and animals on tasks that are behaviorally equivalent (criterion #1) ( Shore et al, 2001 ; see also Gabel et al, 2016 ) and measures visuo-spatial abilities, a cognitive domain for which FXS individuals and KO mice show impairments as compared to their respective control groups (condition #2) (e.g., Crowe and Hay, 1990 ; Cornish et al, 1998 , 1999 ; Kogan et al, 2004a ). We compared the performance of affected humans and mice across multiple conditions and measures to evaluate whether the paradigm engages comparable cognitive mechanisms in both species (criterion #3).…”

“…These two mazes also produced consistent results in humans and mice in terms of difficulty for the visual cue condition. At the time of this writing, we retrieved only two studies that have directly compared humans and mice on the Hebb–Williams maze paradigm ( Shore et al, 2001 ; Gabel et al, 2016 ). These studies also report heterogeneous cross-species consistencies across mazes tested in typically developing participants.…”

“…Drawing from the literature ( Willner, 1986 ; Gilmour et al, 2013 ; McGonigle and Ruggeri, 2014 ; Gabel et al, 2016 ), we propose that to allow for appropriate extrapolation from animal to human studies, translational paradigms must: (1) allow direct comparison of humans and animals on tasks that are behaviorally equivalent, (2) measure constructs that are fundamental to the disorder, and (3) engage comparable underlying neural mechanisms and cognitive functions in both species 2 . To our knowledge, only three studies have directly compared the performance of FXS humans and KO mouse on behaviorally equivalent paradigms ( Frankland et al, 2004 ; Koekkoek et al, 2005 ; MacLeod et al, 2010 ; see, e.g., Gilmour et al, 2013 ; Gabel et al, 2016 for other conditions). Two studies ( Frankland et al, 2004 ; Koekkoek et al, 2005 ) employed paradigms that measure prepulse inhibition, a function that is thought to be impaired in FXS as indicated by heightened sensitivity to sensory stimulation (mouse: Chen and Toth, 2001 ; humans: Miller et al, 1999 ).…”

Reading Disability: Current Practices for Learning

“…Because a child needs to pay attention to reading, this attention is activated in the prefrontal cortex which is the area of the brain that helps the child maintain focus [7]. Gabel et al (2016) [8] state that Reading Disability (RD), "is an early-onset neurodevelopmental disorder, therefore early detection and intervention are necessary to improve individual outcomes" (p. 320).…”