Fiber-specific structural properties relate to reading skills in children and adolescents

  1. Steven Lee Meisler  Is a corresponding author
  2. John DE Gabrieli
  1. Program in Speech and Hearing Bioscience and Technology, Harvard Medical School, United States
  2. McGovern Institute for Brain Research, United States
4 figures, 2 tables and 3 additional files

Figures

Methodological overview of the study.

Top: description of primary and secondary analyses. Bottom: schematic depicting interpretations of changes in examined metrics. Depictions of bundles, axons, and neurites are not drawn to scale. …

Figure 2 with 2 supplements
Age-standardized TOWRE subscores of all participants.

Each dot represents a participant, color-coded by group assignment. Dashed lines mark the score cutoffs for the two reading proficiency groups. Since scores are discrete and not unique, some dots …

Figure 2—figure supplement 1
Correlations between continuous phenotypic and neuroimaging variables.

Correlation coefficients are reported as Spearman’s ρ. p-values were FDR Benjamini–Hochberg adjusted across tests. *p<0.05; **p<0.001; ***p<1e-5. TOWRE, Tests of Word Reading Efficiency composite …

Figure 2—figure supplement 2
ANOVA results for site-wise comparisons between phenotypic and neuroimaging metrics.

Only metrics associated with a significant between-sites ANOVA (p<0.05) are plotted. For t-tests between sites, *p<0.05, **p<0.01, ***p<1e-03, and ****p<1e-04. SES, socioeconomic status; ICV, …

Figure 3 with 4 supplements
Significant fixels (qFDR<0.05) for relating fiber density and cross-section product (FDC) to raw composite Tests of Word Reading Efficiency (TOWRE) scores, colored by effect size (ΔRadj2).

Model confounds included a spline fit for age and linear fits for sex, site, neighbor correlation, and log(ICV). Top and bottom panels are left and right hemispheres, respectively. Sagittal slices …

Figure 3—figure supplement 1
Significant fixels (qFDR<0.05) relating fiber density and cross-section product (FDC) to raw composite Tests of Word Reading Efficiency (TOWRE) scores, colored by the beta estimates (top) and direction (bottom; red, LR; green, AP; blue, SI).

Model confounds included a spline fit for age and linear fits for sex, site, neighbor correlation, and log(ICV). Only the left hemisphere is shown. Sagittal slices go from lateral-to-medial. The …

Figure 3—figure supplement 2
Plots of the set of tracts in which the strongest effect sizes (ΔRadj2>0.028) were achieved for relating fiber density and cross-section product (FDC) to Tests of Word Reading Efficiency (TOWRE) scores (see Table 2).

All tracts were in the left hemisphere. Sagittal slices go from lateral-to-medial. Tracts were segmented from and are plotted on top of the fiber orientation distribution (FOD) template.

Figure 3—figure supplement 3
Significant fixels (qFDR<0.05) relating fiber cross-section (FC; top), and fiber density (FD; bottom) to raw composite Tests of Word Reading Efficiency (TOWRE) scores, colored by direction (red, LR; green, AP; blue, SI).

Model confounds included a spline fit for age and linear fits for sex, site, and neighbor correlation. Additionally, FC included an additional regressor for log(ICV). Only the left hemisphere is …

Figure 3—figure supplement 4
Significant fixels (qFDR<0.05) relating fiber density and cross-section product (FDC) to raw Sight Word Efficiency (SWE; top) and Phonemic Decoding Efficiency (PDE; bottom) subscores, colored by effect size (ΔRadj2).

Model confounds included a spline fit for age and linear fits for sex, site, neighbor correlation, and log(ICV). Only the left hemisphere is shown. Sagittal slices go from lateral-to-medial. The …

Significant fixels (qFDR<0.05) for relating neurite orientation density and dispersion index (NODDI) metrics to raw composite Tests of Word Reading Efficiency (TOWRE) scores, colored by direction (red, LR; green, AP; blue, SI).

Model confounds included a spline fit for age and linear fits for sex, site, neighbor correlation, and log(ICV). Top and bottom panels are the indexes for orientation dispersion (ODI) and neurite …

Tables

Table 1
Phenotypic and neuroimaging summary statistics in all participants and within the two reading proficiency groups.

17 and 93 participants were lacking socioeconomic and WISC scores, respectively, and were ignored for the corresponding rows. Values are listed as mean (standard error of the mean). For group …

MetricAll (n = 983)TR (n = 570)RD (n = 102)Effect size
Sex (M/F)617/366355/21559/43Φ = 0.0235
Age (years)11.16 (0.10)11.38 (0.14)10.56 (0.27)d = 0.258*
Handedness (EHI)61.78 (1.58)62.19 (2.05)62.91 (5.05)d = 0.015
Handedness (L/A/R)74/128/78142/66/4628/17/77Φ = 0.047
SES (years parental edu.)17.63 (0.10)18.13 (0.11)16.93 (0.32)d = 0.429†
ICV (cm3)1540 (5.130)1559 (6.735)1501 (12.47)d = 0.370†
WISC VSI102.08 (0.552)105.72 (0.714)97.82 (1.497)d = 0.494†
WISC VCI104.61 (0.542)109.26 (0.658)98.18 (1.414)d = 0.750†
TOWRE97.93 (0.56)109.49 (0.45)70.48 (0.80)d = 3.74†
Global FD0.285 (6.26e-4)0.287 (7.66e-4)0.280 (2.53e-3)d = 0.337*
Global log(FC)0.050 (2.15e-3)0.059 (2.73e-3)0.030 (5.92e-3)d = 0.455†
Mean motion (mm)0.44 (7.89e-3)0.44 (0.01)0.44 (0.03)d = 4.27e-3
Quality (Neighbor Corr.)0.756 (1.58e-3)0.760 (2.08e-3)0.745 (5.17e-3)d = 0.291*
  1. TR = typically reading group; RD = reading disability group; EHI = Edinburgh Handedness Inventory; SES = socioeconomic status; ICV = intracranial volume; TOWRE = Tests of Word Reading Efficiency composite score, age-normalized; WISC VSI = Wechsler Intelligence Scale for Children visuospatial index, age-normalized; WISC VCI = Wechsler Intelligence Scale for Children verbal comprehension index, age-normalized; FD = fiber density; FC = fiber cross-section. FD and FC are unitless.

Table 2
Intersections of white matter tracts with significant fixels for correlations between fiber density and cross-section product (FDC) and reading skill.

The number of fixels is present for two significance thresholds. For tracts that exist bilaterally, results are given in the form of left/right. Tracts in which the maximum effect size (ΔRadj2) exceeded …

TractN fixels (qFDR<0.05)N fixels (qFDR<0.001)Max effect size (ΔRadj2)
AF2446/1571186/00.030/0.020
ATR114/2970/00.017/0.017
CA31420.018
CC_15300.015
CC_2135100.018
CC_319700.015
CC_4177030.021
CC_5148400.015
CC_62022320.024
CC_725000.018
CG298/2270/00.018/0.019
CST2561/178990/1090.024/0.024
FPT3171/2809214/2210.024/0.024
FX348/3006/60.024/0.024
ICP675/6142/250.023/0.022
IFOF1205/105626/00.024/0.018
ILF811/42227/00.021/0.019
MCP2043220.022
MLF1631/824101/00.029/0.020
OR585/59618/00.021/0.016
POPT2785/2103118/1190.024/0.021
SCP1453/137885/760.029/0.021
SLF I668/9035/40.019/0.020
SLF II918/101550/00.029/0.020
SLF III741/415116/00.030/0.019
ST_FO185/1250/00.019/0.013
ST_OCC862/87226/20.024/0.018
ST_PAR1857/129515/00.024/0.020
ST_POSTC1463/5829/00.020/0.016
ST_PREC1854/67117/20.024/0.016
ST_PREF825/5370/00.019/0.017
ST_PREM214/950/00.019/0.018
STR1035/5313/20.017/0.014
T_OCC625/61717/00.021/0.017
T_PAR1436/6854/00.020/0.016
T_POSTC1086/3830/00.017/0.015
T_PREC1497/6075/20.021/0.014
T_PREF748/5050/00.018/0.017
T_PREM51/1430/00.012/0.014
UF665/40623/00.021/0.016
  1. .

  2. AF = arcuate fasciculus; MLF = middle longitudinal fasciculus; SCP = superior cerebellar peduncles; SLF = superior longitudinal fasciculus.

  3. Please refer to Figure 3 of the TractSeg publication (Wasserthal et al., 2018a) for a full list of the tract abbreviations.

Additional files

MDAR checklist
https://cdn.elifesciences.org/articles/82088/elife-82088-mdarchecklist1-v2.docx
Transparent reporting form
https://cdn.elifesciences.org/articles/82088/elife-82088-transrepform1-v2.pdf
Supplementary file 1

ANOVA results for site-wise comparisons between phenotypic and neuroimaging metrics.

Group comparison columns list significant t-statistics. *p<0.05 for the ANOVA between all sites. Post hoc t-tests were only run if the between-sites ANOVA was significant. Only significant t-statistics (p<0.05) are shown in the table. A positive t-statistic denotes Site 1 > Site 2. EHI, Edinburgh Handedness Inventory; SES, socioeconomic status; ICV, intracranial volume; TOWRE, Tests of Word Reading Efficiency composite score, age-normalized; WISC VSI, Wechsler Intelligence Scale for Children visuospatial index, age-normalized; WISC VCI, Wechsler Intelligence Scale for Children verbal comprehension index, age-normalized; gFD, globally averaged fiber density; gFC, globally averaged fiber cross-section.

https://cdn.elifesciences.org/articles/82088/elife-82088-supp1-v2.pdf

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