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Several observations suggest an impact of prematurity on the claustrum. First, the claustrum's development appears to depend on transient subplate neurons of intra-uterine brain development, which are affected by prematurity. Second, the claustrum is the most densely connected region of the mammalian forebrain relative to its volume; due to its effect on pre-oligodendrocytes, prematurity impacts white matter connections and thereby the development of sources and targets of such connections, potentially including the claustrum. Third, due to its high connection degree, the claustrum contributes to general cognitive functioning (e.g., selective attention and task switching/maintaining); general cognitive functioning, however, is at risk in prematurity. Thus, we hypothesized altered claustrum structure after premature birth, with these alterations being associated with impaired general cognitive performance in premature born persons. Using T1-weighted and diffusion-weighted magnetic resonance imaging in 70 very preterm/very low-birth-weight (VP/VLBW) born adults and 87 term-born adults, we found specifically increased mean diffusivity in the claustrum of VP/VLBW adults, associated both with low birth weight and at-trend with reduced IQ. This result demonstrates altered claustrum microstructure after premature birth. Data suggest aberrant claustrum development, which is potentially related with aberrant subplate neuron and forebrain connection development of prematurity., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Premature birth is associated with alterations in brain structure, particularly in white matter. Among white matter, alterations in cortico-thalamic connections are present in premature-born infants, and they have been suggested both to last until adulthood and to contribute to impaired cognitive functions. To test these hypotheses, 70 very premature-born adults and 67 full-term controls underwent cognitive testing and diffusion-weighted imaging. Each cortical hemisphere was parcellated into six lobes, from which probabilistic tractography was performed to the thalamus. Connection probability was chosen as metric of structural connectivity. We found increased cortico-thalamic connection probability between left prefrontal cortices and left medio-dorsal thalamus and reduced connection probability between bilateral temporal cortices and bilateral anterior thalami in very premature-born adults. Aberrant prefronto- and temporo-thalamic connection probabilities were correlated with birth weight and days on ventilation, respectively, supporting the suggestion that these connectivity changes relate with the degree of prematurity. Moreover, an increase in left prefronto-thalamic connection probability also correlated with lower verbal comprehension index indicating its relevance for verbal cognition. Together, our results demonstrate that cortico-thalamic structural connectivity is aberrant in premature-born adults, with these changes being linked with impairments in verbal cognitive abilities. Due to corresponding findings in infants, data suggest aberrant development of cortico-thalamic connectivity after premature birth with lasting effects into adulthood., Competing Interests: Declaration of competing interest The authors report no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Premature-born adults exhibit lasting white matter alterations as demonstrated by widespread reduction in fractional anisotropy (FA) based on diffusion-weighted imaging (DWI). FA reduction, however, is non-specific for microscopic underpinnings such as aberrant myelination or fiber density (FD). Using recent advances in DWI, we tested the hypothesis of reduced FD in premature-born adults and investigated its link with the degree of prematurity and cognition. 73 premature- and 89 mature-born adults aged 25-27 years underwent single-shell DWI, from which a FD measure was derived using convex optimization modeling for microstructure informed tractography (COMMIT). Premature-born adults exhibited lower FD in numerous tracts including the corpus callosum and corona radiata compared to mature-born adults. These FD alterations were associated with both the degree of prematurity, as assessed via gestational age and birth weight, as well as with reduced cognition as measured by full-scale IQ. Finally, lower FD overlapped with lower FA, suggesting lower FD underlie unspecific FA reductions. Results provide evidence that premature birth leads to lower FD in adulthood which links with lower full-scale IQ. Data suggest that lower FD partly underpins FA reductions of premature birth but that other processes such as hypomyelination might also take place.

Preterm birth is a leading cause for impaired neurocognitive development with an increased risk for persistent cognitive deficits in adulthood. In newborns, preterm birth is associated with interrelated white matter (WM) alterations and deep gray matter (GM) loss; however, little is known about the persistence and relevance of these subcortical brain changes. We tested the hypothesis that the pattern of correspondent subcortical WM and GM changes is present in preterm-born adults and has a brain-injury-like nature, i.e., it predicts lowered general cognitive performance. Eighty-five preterm-born and 69 matched term-born adults were assessed by diffusion- and T1-weighted MRI and cognitive testing. Main outcome measures were fractional anisotropy of water diffusion for WM property, GM volume for GM property, and full-scale IQ for cognitive performance. In preterm-born adults, reduced fractional anisotropy was widely distributed ranging from cerebellum to brainstem to hemispheres. GM volume was reduced in the thalamus, striatum, temporal cortices, and increased in the cingulate cortices. Fractional anisotropy reductions were specifically associated with GM loss in thalamus and striatum, with correlation patterns for both regions extensively overlapping in the WM of brainstem and hemispheres. For overlap regions, fractional anisotropy was positively related with both gestational age and full-scale IQ. Results provide evidence for extensive, interrelated, and adverse WM and GM subcortical changes in preterm-born adults. Data suggest persistent brain-injury-like changes of subcortical-cortical connectivity after preterm delivery.

White matter (WM) injury, either visible on conventional magnetic resonance images (MRI) or measurable by diffusion tensor imaging (DTI), is frequent in preterm born individuals and often affects the corticospinal tract (CST). The relation between visible and invisible white mater alterations in the reconstructed CST of preterm subjects has so far been studied in infants, children and up to adolescence. Therefore, we probabilistically tracked the CST in 53 term-born and 56 very preterm and/or low birth weight (VP/VLBW, < 32 weeks of gestation and/or birth weight < 1,500 g) adults (mean age 26 years) and compared their DTI parameters (axial, radial, mean diffusivity--AD, RD, MD, fractional anisotropy--FA) in the whole CST and slice-wise along the CST. Additionally, we used the automatic, tract-based-spatial-statistics (TBSS) as an alternative to tractography. We compared control and VP/VLBW and subgroups with and without CST WM lesions visible on conventional MRI. Compared to controls, VP/VLBW subjects had significantly higher diffusivity (AD, RD, MD) in the whole CST, slice-wise along the CST, and in multiple regions along the TBSS skeleton. VP/VLBW subjects also had significantly lower (TBSS) and higher (tractography) FA in regions along the CST, but no different mean FA in the tracked CST as a whole. Diffusion changes were weaker, but remained significant for both, tractography and TBSS, when excluding subjects with visible CST lesions. Chronic CST injury persists in VP/VLBW adults even in the absence of visible WM lesions, indicating long-term structural WM changes induced by premature birth., (© 2015 Wiley Periodicals, Inc.)