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. 2020;25:102194.
doi: 10.1016/j.nicl.2020.102194. Epub 2020 Jan 22.

Rewiring the Extremely Preterm Brain: Altered Structural Connectivity Relates to Language Function

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Free PMC article

Rewiring the Extremely Preterm Brain: Altered Structural Connectivity Relates to Language Function

Maria E Barnes-Davis et al. Neuroimage Clin. .
Free PMC article

Abstract

Children born preterm are at increased risk for cognitive impairment, with higher-order functions such as language being especially vulnerable. Previously, we and others have reported increased interhemispheric functional connectivity in children born extremely preterm; the finding appears at odds with literature showing decreased integrity of the corpus callosum, the primary commissural bundle, in preterm children. We address the apparent discrepancy by obtaining advanced measures of structural connectivity in twelve school-aged children born extremely preterm (<28 weeks) and ten term controls. We hypothesize increased extracallosal structural connectivity might support the functional hyperconnectivity we had previously observed. Participants were aged four to six years at time of study and groups did not differ in age, sex, race, ethnicity, or socioeconomic status. Whole-brain and language-network-specific (functionally-constrained) connectometry analyses were performed. At the whole-brain level, preterm children had decreased connectivity in the corpus callosum and increased connectivity in the cerebellum versus controls. Functionally-constrained analyses revealed significantly increased extracallosal connectivity between bilateral temporal regions in preterm children (FDRq <0.05). Connectivity within these extracallosal pathways was positively correlated with performance on standardized language assessments in children born preterm (FDRq <0.001), but unrelated to performance in controls. This is the first study to identify anatomical substrates for increased interhemispheric functional connectivity in children born preterm; increased reliance on an extracallosal pathway may represent a biomarker for resiliency following extremely preterm birth.

Keywords: Connectivity; Development; Diffusion; Language; Prematurity.

Conflict of interest statement

Declaration of Competing Interest None.

Figures

Fig. 1
Fig. 1
Whole-Brain Between-Groups Comparison, Control > Preterm. Tracks in which connectivity was significantly greater for TC children compared to EPT children. Notable tracks include those through the corpus callosum. All connectometry analyses result in subcomponents of pathways that are significantly associated with the study variable, but are not necessarily entire fascicles. Results are color coded for the local directionality of the tracts and colors change along the track as it changes directionality along the path (red = left/right, green = anterior/posterior, blue = inferior/superior). The background image for all figures is a surface rendering of a standard space T1 image from the study specific template warped from MNI space. Results are viewed in a transparent surface rendering, showing tracks from three points of view: left sagittal, front coronal, right sagittal. These views aid visualization because they show the relative depth of the tracks resolved and ensure no tracks are occluded by tracks from the contralateral hemisphere. The length threshold used to determine FDRq < 0.05 was 30 mm.
Fig. 2
Fig. 2
Whole-Brain Between-Groups Comparison, Preterm > Control. Tracks in which connectivity was significantly greater for EPT than TC. Results include white matter within both hemispheres of the cerebellum. The length threshold used to determine FDRq < 0.05 was 30 mm.
Fig. 3
Fig. 3
Receptive Language Network Group Comparison, Control > Preterm. Receptive language network connectometry analysis showing the relationship between group (TC vs. EPT) and white matter connectivity. Results show tracks where TC > EPT, which are widely distributed (FDRq < 0.05). The length threshold used to determine FDRq < 0.05 was 30 mm.
Fig. 4
Fig. 4
Receptive Language Network Group Comparison, Preterm > Control. Receptive language network connectometry analysis showing the relationship between group (TC vs. EPT) and white matter connectivity. Results show tracks where EPT > TC, including bilateral corticospinal pathways, bilateral external capsules, left corticothalamic pathways, left corticopontine pathways, and bilateral middle cerebellar peduncles. Tract directionality is inferred from known anatomy of the significant tracts resolved. The length threshold used to determine FDRq < 0.05 was 30 mm.
Fig. 5
Fig. 5
Receptive Language Network Group Comparison while Controlling Group Differences in Performance. Receptive language network connectometry analysis showing the relationship between group (TC vs. EPT) and white matter connectivity while controlling for differences in language performance between groups (FDRq < 0.05). Results show tracks where EPT > TC including bilateral corticospinal pathways, bilateral external capsules, left corticothalamic pathway, bilateral middle cerebellar peduncles, and cerebellar white matter within the right hemisphere. There were no tracks where TC > EPT (FDRq > 0.05). Tract directionality is inferred from known anatomy of the significant tracts resolved. The length threshold used to determine FDRq < 0.05 was 30 mm.
Fig. 6
Fig. 6
Language Performance within EPT: Whole Brain. Whole-brain connectometry analysis showing the relationship between language performance and white matter connectivity within the EPT group. Results show widespread positive associations with language performance (FDRq < 0.05). There were no tracks with a negative correlation with language performance. Tract directionality is inferred from known anatomy of the significant tracts resolved. The length threshold used to determine FDRq < 0.05 was 30 mm.
Fig. 7
Fig. 7
Language Performance within EPT: Receptive Network. Receptive language network connectometry analysis showing the relationship between language performance and white matter connectivity within the EPT group. Results show widespread positive associations with language performance (FDRq < 0.05). These tracks encompass most of the white matter in the receptive language network with too many pertinent tracks resolved to clearly label, so we focused on the finding most vital to our paper: the track from the right cerebellum to the left corticopontine fiber pathway. There were no connectomes with a negative correlation with language performance. Tract directionality is inferred from known anatomy of the significant tracts resolved. The length threshold used to determine FDRq < 0.05 was 30 mm.

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