Interhemispheric temporal lobe connectivity predicts language impairment in adolescents born preterm

Abstract

Although language difficulties are common in children born prematurely, robust neuroanatomical correlates of these impairments remain to be established. This study investigated whether the greater prevalence of language problems in preterm (versus term-born) children might reflect injury to major intra- or interhemispheric white matter pathways connecting frontal and temporal language regions. To investigate this, we performed a comprehensive assessment of language and academic abilities in a group of adolescents born prematurely, some of whom had evidence of brain injury at birth (n = 50, mean age: 16 years, mean gestational age: 27 weeks) and compared them to a term-born control group (n = 30). Detailed structural magnetic resonance imaging and diffusion-tractography analyses of intrahemispheric and interhemispheric white matter bundles were performed. Analysis of intrahemispheric pathways included the arcuate fasciculus (dorsal language pathway) and uncinate fasciculus/extreme capsule (ventral language pathway). Analysis of interhemispheric pathways (in particular, connections between the temporal lobes) included the two major commissural bundles: the corpus callosum and anterior commissure. We found language impairment in 38% of adolescents born preterm. Language impairment was not related to abnormalities of the arcuate fasciculus (or its subsegments), but was associated with bilateral volume reductions in the ventral language pathway. However, the most significant volume reduction was detected in the posterior corpus callosum (splenium), which contains interhemispheric connections between the occipital, parietal and temporal lobes. Diffusion tractography showed that of the three groups of interhemispheric fibres within the splenium, only those connecting the temporal lobes were reduced. Crucially, we found that language impairment was only detectable if the anterior commissure (a second temporal lobe commissural pathway) was also small. Regression analyses showed that a combination of anatomical measures of temporal interhemispheric connectivity (through the splenium of the corpus callosum and anterior commissure) explained 57% of the variance in language abilities. This supports recent theories emphasizing the importance of interhemispheric connections for language, particularly in the developing brain.

Figure 1

Language-relevant white matter pathways and regions of vulnerability in the preterm brain. Left: Intrahemispheric language tracts, the uncinate fasciculus/extreme capsule, arcuate fasciculus and its subsegments (red: direct segment; green: anterior segment; yellow: posterior segment). Bottom left: Example cases with periventricular white matter injury in proximity to the arcuate fasciculus (arrows). Right: Interhemispheric bundles traversing the splenium of the corpus callosum (red: connecting the temporal lobes; blue: connecting the occipital lobes; yellow: between parietal lobes) and the anterior commissure (connecting the anterior temporal lobes of both hemispheres). Bottom right: Example case with severe reduction of the posterior corpus callosum, including the splenium (upper arrow), and of the anterior commissure (lower arrow).

Figure 2

Corpus callosum reduction in the language-impaired preterm group. Left: Voxel-based morphometry (VBM) analysis identified two focal regions of white matter volume reduction in language-impaired individuals in the region of the posterior corpus callosum (splenium) extending into the left temporal lobe. At lower thresholds, this cluster also extended into the right temporal white matter. Colour coding indicates different statistical thresholds: yellow: P < 0.05, family wise error-corrected for multiple comparisons, red: P < 0.001, uncorrected. Right: Manual measurements of the area of corpus callosum segments [according to Hofer and Frahm (2006)] confirmed pronounced reduction in segment V. Post hoc comparisons between preterm groups with and without language impairment (covariate: global white matter volume) are indicated by **P < 0.0001, *P < 0.05 (all Bonferroni corrected). CC = corpus callosum.

Figure 3

DWI-tractography of the arcuate fasciculus. Identification of the direct segment in representative cases illustrates the lack of a robust relationship between tract volume and language outcome in the preterm cohort. Arcuate fasciculi in both hemispheres are shown for one control (left side) and four preterm adolescents (Cases 1–4). The projection of the whole tract is shown on representative slices of T₁-weighted MRI scans. Preterm cases had varying degrees of ventricular dilatation (white arrows). Language impairment was found in cases with no MRI abnormalities and normal arcuate fasciculus volume in the left hemisphere (Case 1).

Figure 4

Interhemispheric connectivity and language impairment. DWI-tractography of the posterior transcallosal fibre connections between the parietal lobes (shown in yellow), occipital lobes (blue) and temporal lobes (red) in one term-born control case (displayed on a T₁-weighted MRI scan on left side) and three preterm adolescents (Cases A–C), all males aged 16–18 years. The projections of the whole tracts are shown. The mid-saggital section of the corpus callosum and the distribution of the fibre bundles are displayed on fractional anisotropy maps (top row). The size the anterior commissure (AC) is also shown on T₁-weighted MRI (bottom row). Case A: Language outcome was unimpaired (CELF-3^UK language score = 101, 11 points higher than performance IQ). Both interhemispheric connections between the temporal lobes were intact. Case B: Despite severely reduced temporal lobe fibres (red arrow), language was not impaired (CELF-3^UK language score = 99, 13 points higher than performance IQ). The size of anterior commissure was intact. Note, this patient is also shown in Fig. 2 (Case 2) with bilaterally reduced arcuate fasciculi. Case C: Language was impaired (CELF-3^UK language score = 78, 23 points lower than performance IQ). Reduction of both temporal lobe fibres and the anterior commissure is visible, with intact parietal and occipital connections. This case is also shown in Fig. 2 (Case 1), with intact left arcuate fasciculus.