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. 2022 Sep 27:11:e74242.
doi: 10.7554/eLife.74242.

Quantitative MRI reveals differences in striatal myelin in children with DLD

Saloni Krishnan  1   2 , Gabriel J Cler  1   3 , Harriet J Smith  1   4 , Hanna E Willis  1   5 , Salomi S Asaridou  1 , Máiréad P Healy  1   6 , Daniel Papp  7   8 , Kate E Watkins  1
Affiliations

Quantitative MRI reveals differences in striatal myelin in children with DLD

Saloni Krishnan et al. Elife. .

Abstract

Developmental language disorder (DLD) is a common neurodevelopmental disorder characterised by receptive or expressive language difficulties or both. While theoretical frameworks and empirical studies support the idea that there may be neural correlates of DLD in frontostriatal loops, findings are inconsistent across studies. Here, we use a novel semiquantitative imaging protocol - multi-parameter mapping (MPM) - to investigate microstructural neural differences in children with DLD. The MPM protocol allows us to reproducibly map specific indices of tissue microstructure. In 56 typically developing children and 33 children with DLD, we derived maps of (1) longitudinal relaxation rate R1 (1/T1), (2) transverse relaxation rate R2* (1/T2*), and (3) Magnetization Transfer saturation (MTsat). R1 and MTsat predominantly index myelin, while R2* is sensitive to iron content. Children with DLD showed reductions in MTsat values in the caudate nucleus bilaterally, as well as in the left ventral sensorimotor cortex and Heschl's gyrus. They also had globally lower R1 values. No group differences were noted in R2* maps. Differences in MTsat and R1 were coincident in the caudate nucleus bilaterally. These findings support our hypothesis of corticostriatal abnormalities in DLD and indicate abnormal levels of myelin in the dorsal striatum in children with DLD.

Keywords: SLI; caudate nucleus; children; histological MRI; human; language impairment; microstructure; neurodevelopmental disorder; neuroscience; qMRI; speech motor.

Plain language summary

Seven percent of children struggle to learn their native language for no obvious reason. This condition is called Developmental Language Disorder (DLD). Children with DLD often have difficulty learning to read and write. They are at higher risk for academic underachievement and may struggle to find good jobs. Their language difficulties also contribute to difficulties making friends and emotional challenges. Scientists suspect children with DLD may have differences in areas deep in the brain that help people learn habits and rules. A new magnetic resonance imaging technique called multiparameter mapping (MPM) can help scientists determine if this is true. The technique measures the properties of brain tissue. It is particularly useful for measuring the amounts of a fatty protective sheath on brain cells called myelin. Myelin helps brain cells send information faster. Using MPM, Krishnan et al. show that children with DLD have less myelin in parts of the brain responsible for speaking, listening, and learning rules and habits. In the experiments, 56 children with typical language development and 33 children with DLD were scanned using MPM. Krishnan et al. then compared the two groups and found reduced myelin in these critical areas associated with learning a language in most of the children with DLD. But not all children with DLD had these differences. More studies are needed to determine if these brain differences cause language problems and how or if experiencing language difficulties could cause these changes in the brain. Further research may help scientists find new treatments that target these brain differences.

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Conflict of interest statement

SK, GC, HS, HW, SA, MH, DP, KW No competing interests declared

Figures

Figure 1.
Figure 1.. Brain areas showing reduced Magnetization Transfer saturation (MTsat) in developmental language disorder (DLD).
Coloured maps resampled and overlaid on the fsaverage surface (reconstructed using the HCP workbench) show TD > DLD differences in MTsat values (whole-brain corrected threshold p < 0.05). Axial slices (coloured maps are overlaid on an average MTsat image from all participants) show additional group differences subcortically in the caudate nuclei. The inset shows a boxplot of MTsat values drawn from the cluster in the caudate nuclei by group, with this cluster split into right and left using a hemispheric mask (orange – DLD, green – TD).
Figure 1—figure supplement 1.
Figure 1—figure supplement 1.. Whole-brain typically developing (TD) > developmental language disorder (DLD) differences (thresholded at p < 0.05) when excluding children with nonverbal IQs < 85 in Magnetization Transfer saturation (MTsat) values.
See legend to Figure 1 for details.
Figure 1—figure supplement 2.
Figure 1—figure supplement 2.. Relationship between MTsat values in the caudate nucleus by age and total intracranial volume (TIV) in typically developing (TD) children and those with developmental language disorder (DLD).
Average MTsat in the left and right caudate nucleus for individual participants are plotted against age or TIV. Dots show data for individual participants, colour represents group (orange - DLD, green - TD). All correlations are non-significant (p>.35), as shown by the statistics above.
Figure 2.
Figure 2.. Brain areas showing reduced R1 in developmental language disorder (DLD).
Coloured maps resampled and overlaid on the fsaverage surface (reconstructed using the HCP workbench) show TD > DLD differences in R1 maps (whole-brain corrected threshold p < 0.05). Axial slices (coloured maps are overlaid on an average MTsat image from all participants) show additional subcortical group differences in the striatum and thalamus bilaterally.
Figure 2—figure supplement 1.
Figure 2—figure supplement 1.. Whole-brain typically developing (TD) > developmental language disorder (DLD) differences (thresholded at p < 0.05) when excluding children with nonverbal IQs <85 in R1 values.
See legend to Figure 2 for details.
Figure 3.
Figure 3.. Brain areas showing conjoint reductions in MTsat and R1 in developmental language disorder (DLD).
Coloured maps resampled and overlaid on the fsaverage surface (reconstructed using the HCP workbench) show convergence of TD > DLD differences in MTsat and R1 maps thresholded at p < 0.05. Axial slices (coloured maps are overlaid on an average MTsat image from all participants) show the differences subcortically in the dorsal striatum in particular.
Figure 3—figure supplement 1.
Figure 3—figure supplement 1.. Average MTsat, R1, and R2* values in typically developing (TD) and developmental language disorder (DLD) groups are shown using a coloured heat map (hotter colours show higher values).
Maps are overlaid on the fsaverage surface reconstructed using the HCP workbench. Left (L) and right (R) lateral and medial surfaces are shown on the left and right side of the figure respectively.
Figure 4.
Figure 4.. Correlation between language proficiency and Magnetization Transfer saturation (MTsat) values in the left caudate nucleus.
Coloured maps are overlaid on axial slices through the average MTsat image from all participants (top) showing significant relationship subcortically in the left caudate nucleus. Average MTsat values for the left caudate nucleus in individual participants are plotted against the Language Proficiency Factor score. The solid line is the regression line with shaded areas showing the 95% confidence interval. Groups are plotted in different colours (green - TD, orange - DLD. purple - HSL) for illustration.
Figure 4—figure supplement 1.
Figure 4—figure supplement 1.. Whole-brain correlation of multi-parameter mapping (MPM) values with language proficiency (thresholded at p < 0.05).
See legend to Figure 4 for details.
See this image and copyright information in PMC

Comment in

  • What happens in the brain?
    Smith F, Griffiths TD. Smith F, et al. Elife. 2022 Sep 27;11:e82258. doi: 10.7554/eLife.82258. Elife. 2022. PMID: 36164823 Free PMC article.

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