Maternal history of reading difficulty is associated with reduced language-related gray matter in beginning readers

Abstract

Family history and poor preliteracy skills (referred to here as familial and behavioral risk, respectively) are critical predictors of developmental dyslexia. This study systematically investigated the independent contribution of familial and behavioral risks on brain structures, which had not been explored in past studies. We also examined the differential effects of maternal versus paternal history on brain morphometry, and familial risk dimensionally versus categorically, which were also novel aspects of the study. We assessed 51 children (5 to 6 years of age) with varying degrees of familial and behavioral risks for developmental dyslexia and examined associations with brain morphometry. We found that greater maternal history of reading disability was associated with smaller bilateral prefrontal and parieto-temporal gray, but not white matter volumes. Regressing out behavioral risk, socioeconomic status, and maternal education and other confounds did not change the results. No such relationship was observed for paternal reading history and behavioral risk. Results of cortical surface area and thickness further showed that there was a significant negative relationship between cortical surface area (but not thickness) and greater severity of maternal history, in particular within the left inferior parietal lobule, suggesting prenatal influence of maternal history on children's brain morphometry. The results suggested greater maternal, possibly prenatal, influence on language-related brain structures. These results help to guide future neuroimaging research focusing on environmental and genetic influences and provide new information that may help predict which child will develop dyslexia in the future.

Figure 1. Associations among familial risk index (FamRI), behavioral risk index (BxRI) (marked in black boxes) and various demographic, behavioral and brain measures

Upper left figure represents correlation coefficients (R) and lower right represents significance level (P). Black boxes are shown to easily identify factors that are associated the FamRI and BxRI. In the lower right, comparisons in red (p<0.001) are those that are significant even after Bonferroni correction. Age: child’s age in years, SES: socioeconomic status, IQ: Woodcock Johnson III brief intellectual ability standard score (-ss), VIQ: Woodcock Johnson III verbal comprehension-ss, PIQ: Woodcock Johnson III concept formation-ss, LID: WRMT Letter ID subtest -ss, RN: rapid automatized naming color and object subtests average –ss, PA: phonological awareness composite score of CTOPP, BxRI: composite measure of PA, RN and LID, PM: phonological memory composite score of CTOPP, TGMV: total grey matter volume, TWMV: total white matter volume, Age-M: maternal age, mFamRI: maternal ARHQ score, OT-M: percent overall maternal time with child, ET-M: percent of maternal educational time with child, Ed-M: maternal educational level, IQ-M: maternal estimated full-scale IQ from WAIS-R, VIQ-M: maternal estimated verbal IQ from WAIS-R, PIQ-M: maternal estimated performance IQ from WAIS-R, -P refers to parental scores. For example, one can see that BxRI is negatively correlated LID, RN, and PA (all p’s<0.001). mFamRI is significantly correlated with many other measures in the figure, but pFamRI is not significantly correlated with these measures except for IQ-P, VIQ-P, PIQ-P and child’s VIQ.

Figure 2. Association between regional brain volume and maternal Family Risk Index [mFamRI; FamRI is equivalent to Adult Reading History Questionnaire (ARHQ) scores]

a. Brain regions where there were significant negative association between grey matter volume (GMV) and mFamRI (p<0.05 corrected). Main region and statistical values (t-values, cluster size in voxels [k] and p values) are listed. b. Brain regions where there were significant negative association between GMV and mFamRI. Total GMV and Behavioral Risk Index (BxRI; defined as a composite of letter identification, rapid naming and phonological awareness scores) were entered as nuisance variables (p<0.05 corrected). Main region, peak Talairach coordinates, anatomical structures the clusters extend to, and statistical values (t-values, cluster size in voxels [k] and p values) are listed. c. Visual representation of correlations between FamRI and mean regional GMV of all significant clusters in Fig 1b combined and adjusted for total GMV and BxRI. Results were similar for each cluster hence are combined here. d. Visual representation of correlations between BxRI and mean regional GMV of all significant clusters in Fig 1b combined and adjusted for total GMV and mFamRI. Results were similar for each cluster hence are combined here.

Figure 3. Association between regional brain volume and maternal Family Risk Index (mFamRI; FamRI is equivalent to Adult Reading History Questionnaire [ARHQ] scores)

a. Brain region where there was a trend for significant negative association between white matter volume (WMV) and mFamRI (0.05<p<0.1 corrected). This region was not significant when the Behavioral Risk Index (BxRI; defined as a composite of letter identification [LID], rapid naming [RN] and phonological awareness [PA] scores) was entered as a nuisance variable (p>0.1 corrected). Main region and statistical values (t-values, cluster size in voxels [k] and p values) are listed. b. Brain regions where there were significantly reduced grey matter volume (GMV) in children with mFamRI compared to those without based on ARHQ scores (p<0.05 corrected). Note similarities with Figures 2a and 2b in bilateral prefrontal cortices and right parieto-temporal regions. Note also the lack of left parieto-temporal region (t=3.69, k=2425, p=0.13 corrected), and addition of the right temporal regions. c. Brain regions where there were significantly reduced GMV in children with a maternal family history of reading disability compared to those with paternal family history based on ARHQ scores (p<0.05 corrected). Note spatial overlap with the left parieto-temporal region in Figure 2a.

Figure 4. Visual representation of correlations between Family Risk Index (FamRI) and mean regional grey matter volume (GMV) of all significant clusters in Figure 2b combined and adjusted for total GMV and behavioral risk index (Bx RI)

Results were similar for each cluster hence are combined here. Red filled circles and blue squares represent those children who either a. spent more education-related time with father (of these, only one spent total time more with their father), which showed similar effects as plotting those who spent more total time with father, b. are left-handed, c. first-graders at the time of testing, or d. were in Phase I (entered study in 2008 Summer) as opposed to Phase II (entered study in 2009 Summer). While the plots only show qualitatively how these factors were not driving our results, the results are consistent with the primary analyses where we regressed out these effects (a, b, c and d) or excluded these particular children from the analyses (a, b and c).

Figure 5. Association between cortical surface area and thickness of the left inferior parietal lobule and maternal reading history

Lt IPL: left inferior parietal lobule, ARHQ: Adult Reading History Questionnaire.