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

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Tables
Additional files

4 figures, 2 tables and 3 additional files

Figures

Figure 1

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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. DWI, diffusion-weighted imaging; DTI, diffusion tensor imaging; DKI, diffusion kurtosis imaging; NODDI, neurite orientation density and dispersion index; FA, fractional anisotropy; KFA, kurtosis fractional anisotropy; MD, mean diffusivity; MK, mean kurtosis; NDI, neurite density index; ODI, orientation dispersion index; FODF, fiber orientation distribution function; FD, fiber density; FC, fiber cross-section; FDC, fiber density and cross-section product.

Figure 2 with 2 supplements

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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 may overlap with each other. Kernel density estimation plots along the perimeter show the distribution of reading scores in each group. TR, typically reading group; RD, reading disability group; TOWRE, Tests of Word Reading Efficiency.

Figure 2—figure supplement 1

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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 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; SES, socioeconomic status; ICV, intracranial volume; N Corr, neighbor correlation; gFD, globally averaged fiber density; gFC, globally averaged fiber cross-section.

Figure 2—figure supplement 2

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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, intracranial volume; WISC VSI, Wechsler Intelligence Scale for Children visuospatial index, age-normalized; WISC VCI, Wechsler Intelligence Scale for Children verbal comprehension index, age-normalized; N Corr, neighbor correlation; gFD, globally averaged fiber density; gFC, globally averaged fiber cross-section.

Figure 3 with 4 supplements

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Significant fixels ( $q_{F D R} < 0.05$ ) for relating fiber density and cross-section product (FDC) to raw composite Tests of Word Reading Efficiency (TOWRE) scores, colored by effect size ( $Δ R_{a d j}^{2}$ ).

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 go from lateral-to-medial. Blue arrows point to larger clusters of fixels in bilateral temporoparietal and cerebellar white matter that were associated with higher effect sizes relative to fixels in the rest of the hemisphere. The template fiber orientation distribution (FOD) image was used as the background image.

Figure 3—figure supplement 1

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Significant fixels ( $q_{F D R} < 0.05$ ) 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 template fiber orientation distribution (FOD) image was used as the background image.

Figure 3—figure supplement 2

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Plots of the set of tracts in which the strongest effect sizes ( $Δ R_{a d j}^{2} > 0.028$ ) 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

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Significant fixels ( $q_{F D R} < 0.05$ ) 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 shown. Sagittal slices go from lateral-to-medial. Blue arrows point to larger clusters of significant fixels in temporoparietal and cerebellar white matter that overlapped with significant results in the main fiber density and cross-section product (FDC) analysis. The template fiber orientation distribution (FOD) image was used as the background image.

Figure 3—figure supplement 4

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Significant fixels ( $q_{F D R} < 0.05$ ) 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 ( $Δ R_{a d j}^{2}$ ).

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 template fiber orientation distribution (FOD) image was used as the background image.

Figure 4

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Significant fixels ( $q_{F D R} < 0.05$ ) 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 density (NDI), respectively. Only the left hemisphere is shown. Sagittal slices go from lateral-to-medial. Blue arrows and circles indicate significant fixels. The template fiber orientation distribution (FOD) image was used as the background image.

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 comparison effect sizes (right-most column), *p<0.05 and † p<0.001. All t-tests were Welch’s t-tests, and $χ^{2}$ tests were used for comparisons of categorical variables.

Metric	All (n = 983)	TR (n = 570)	RD (n = 102)	Effect size
Sex (M/F)	617/366	355/215	59/43	Φ = 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)	74/128/781	42/66/462	8/17/77	Φ = 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 VSI	102.08 (0.552)	105.72 (0.714)	97.82 (1.497)	d = 0.494†
WISC VCI	104.61 (0.542)	109.26 (0.658)	98.18 (1.414)	d = 0.750†
TOWRE	97.93 (0.56)	109.49 (0.45)	70.48 (0.80)	d = 3.74†
Global FD	0.285 (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*

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 ( $Δ R_{a d j}^{2}$ ) exceeded 0.028 are designated with a bold font. This only happened in the left hemisphere. Tract masks are not mutually exclusive, and nearby tracts likely overlapped to various degrees.

Tract	N fixels ( $q_{F D R} < 0.05$ )	N fixels ( $q_{F D R} < 0.001$ )	Max effect size ( $Δ R_{a d j}^{2}$ )
AF	2446/1571	186/0	0.030/0.020
ATR	114/297	0/0	0.017/0.017
CA	314	2	0.018
CC_1	53	0	0.015
CC_2	1351	0	0.018
CC_3	197	0	0.015
CC_4	1770	3	0.021
CC_5	1484	0	0.015
CC_6	2022	32	0.024
CC_7	250	0	0.018
CG	298/227	0/0	0.018/0.019
CST	2561/1789	90/109	0.024/0.024
FPT	3171/2809	214/221	0.024/0.024
FX	348/300	6/6	0.024/0.024
ICP	675/614	2/25	0.023/0.022
IFOF	1205/1056	26/0	0.024/0.018
ILF	811/422	27/0	0.021/0.019
MCP	2043	22	0.022
MLF	1631/824	101/0	0.029/0.020
OR	585/596	18/0	0.021/0.016
POPT	2785/2103	118/119	0.024/0.021
SCP	1453/1378	85/76	0.029/0.021
SLF I	668/903	5/4	0.019/0.020
SLF II	918/1015	50/0	0.029/0.020
SLF III	741/415	116/0	0.030/0.019
ST_FO	185/125	0/0	0.019/0.013
ST_OCC	862/872	26/2	0.024/0.018
ST_PAR	1857/1295	15/0	0.024/0.020
ST_POSTC	1463/582	9/0	0.020/0.016
ST_PREC	1854/671	17/2	0.024/0.016
ST_PREF	825/537	0/0	0.019/0.017
ST_PREM	214/95	0/0	0.019/0.018
STR	1035/531	3/2	0.017/0.014
T_OCC	625/617	17/0	0.021/0.017
T_PAR	1436/685	4/0	0.020/0.016
T_POSTC	1086/383	0/0	0.017/0.015
T_PREC	1497/607	5/2	0.021/0.014
T_PREF	748/505	0/0	0.018/0.017
T_PREM	51/143	0/0	0.012/0.014
UF	665/406	23/0	0.021/0.016

.
AF = arcuate fasciculus; MLF = middle longitudinal fasciculus; SCP = superior cerebellar peduncles; SLF = superior longitudinal fasciculus.
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
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Transparent reporting form: https://cdn.elifesciences.org/articles/82088/elife-82088-transrepform1-v2.pdf
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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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Steven Lee Meisler
John DE Gabrieli

(2022)

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

eLife 11:e82088.

https://doi.org/10.7554/eLife.82088

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Methodological overview of the study.

Age-standardized TOWRE subscores of all participants.

Correlations between continuous phenotypic and neuroimaging variables.

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

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 (Δ⁢Ra⁢d⁢j2).

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).

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).

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).

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 (Δ⁢Ra⁢d⁢j2).

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).

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

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

MDAR checklist

Transparent reporting form

Supplementary file 1

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Significant fixels ( $q_{F D R} < 0.05$ ) for relating fiber density and cross-section product (FDC) to raw composite Tests of Word Reading Efficiency (TOWRE) scores, colored by effect size ( $Δ R_{a d j}^{2}$ ).

Significant fixels ( $q_{F D R} < 0.05$ ) 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).

Plots of the set of tracts in which the strongest effect sizes ( $Δ R_{a d j}^{2} > 0.028$ ) were achieved for relating fiber density and cross-section product (FDC) to Tests of Word Reading Efficiency (TOWRE) scores (see Table 2).

Significant fixels ( $q_{F D R} < 0.05$ ) 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).

Significant fixels ( $q_{F D R} < 0.05$ ) 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 ( $Δ R_{a d j}^{2}$ ).

Significant fixels ( $q_{F D R} < 0.05$ ) 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).