Barbara Busch

Correspondence Between Aberrant Intrinsic Network Connectivity and Gray-Matter Volume in the Ventral Brain of Preterm Born Adults

Widespread brain changes are present in preterm born infants, adolescents, and even adults. While neurobiological models of prematurity facilitate powerful explanations for the adverse effects of preterm birth on the developing brain at microscale, convincing linking principles at large-scale level to explain the widespread nature of brain changes are still missing. We investigated effects of preterm birth on the brains large-scale intrinsic networks and their relation to brain structure in preterm born adults. In 95 preterm and 83 full-term born adults, structural and functional magnetic resonance imaging at-rest was used to analyze both voxel-based morphometry and spatial patterns of functional connectivity in ongoing blood oxygenation level-dependent activity. Differences in intrinsic functional connectivity (iFC) were found in cortical and subcortical networks. Structural differences were located in subcortical, temporal, and cingulate areas. Critically, for preterm born adults, iFC-network differences were overlapping and correlating with aberrant regional gray-matter (GM) volume specifically in subcortical and temporal areas. Overlapping changes were predicted by prematurity and in particular by neonatal medical complications. These results provide evidence that preterm birth has long-lasting effects on functional connectivity of intrinsic networks, and these changes are specifically related to structural alterations in ventral brain GM.

Working memory in preterm-born adults: Load-dependent compensatory activity of the posterior default mode network

Premature birth is associated with an increased risk of cognitive performance deficits that are dependent on working memory (WM) load in childhood. Less clear is whether preterm‐born adults show similar WM impairments, or develop compensatory brain mechanisms that help to overcome prematurity‐related functional deficits, for example, by a workload‐dependent over‐recruitment of WM‐typical areas, and/or engagement of alternative brain networks. In this functional magnetic resonance imaging study, 73 adults born very preterm and/or with very low birth weight (VP/VLBW) and 73 term‐born controls (CON, mean age: 26.5 years) performed a verbal N‐Back paradigm with varying workload (0‐back, 1‐back, 2‐back). Generally, both groups showed similar performance accuracy and task‐typical patterns of brain activations (especially in fronto‐cingulo‐parietal, thalamic, and cerebellar areas) and deactivations (especially in mesial frontal and parietal aspects of the default mode network [DMN]). However, VP/VLBW adults showed significantly stronger deactivations (P < 0.05, cluster‐level corrected) than CON in posterior DMN regions, including right ventral precuneus, and right parahippocampal areas (with adjacent cerebellar areas), which were specific for the most demanding 2‐back condition. Consistent with a workload‐dependent effect, VP/VLBW adults with stronger deactivations (1‐back > 2‐back) in the parahippocampal/cerebellar cluster also presented a greater slowing of response latencies with increasing WM load (2‐back > 1‐back), indicative of higher effort. In conclusion, VP/VLBW adults recruited similar anatomical networks as controls during N‐back performance, but showed an enhanced suppression of posterior DMN regions during higher workload, which may reflect a temporary suppression of stimulus‐independent thoughts that helps to maintain adequate task performance with increasing attentional demands. Hum Brain Mapp 36:1121–1137, 2015.

Neural correlates of executive attention in adults born very preterm

Very preterm birth is associated with an increased prevalence of attention problems and may especially impair executive attention, i.e., top-down control of attentional selection in situations where distracting information interferes with the processing of task-relevant stimuli. While there are initial findings linking structural brain alterations in preterm-born individuals with attention problems, the functional basis of these problems are not well understood. The present study used an fMRI adaptation of the Attentional Network Test to examine the neural correlates of executive attention in a large sample of N = 86 adults born very preterm and/or with very low birth weight (VP/VLBW), and N = 100 term-born controls. Executive attention was measured by comparing task behavior and brain activations associated with the processing of incongruent vs. congruent arrow flanker stimuli. Consistent with subtle impairments of executive attention, the VP/VLBW group showed lower accuracy and a tendency for increased response times during the processing of incongruent stimuli. Both groups showed similar activation patters, especially within expected fronto-cingulo-parietal areas, but no significant between-group differences. Our results argue for a maintained attention-relevant network organization in high-functioning preterm born adults in spite of subtle deficits in executive attention. Gestational age and neonatal treatment variables showed associations with task behavior, and brain activation in the dorsal ACC and lateral occipital areas, suggesting that the degree of prematurity (and related neonatal complications) has subtle modulatory influences on executive attention processing.

White matter alterations of the corticospinal tract in adults born very preterm and/or with very low birth weight.

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. Hum Brain Mapp 37:289–299, 2016.

Very Preterm Birth and Parents’ Quality of Life 27 Years Later

We find that VP birth does not lower parents’ quality of life in the long-term. BACKGROUND AND OBJECTIVES: Parents of preterm children experience increased distress early in their children’s lives. Whether the quality of life of parents of preterm children is comparable to that of parents of term children by the time their offspring reach adulthood is unknown. What precursors in their offspring’s childhood predict parental quality of life? METHODS: A prospective whole-population study in Germany followed very preterm (VP) (<32 weeks gestation) or very low birth weight (VLBW) (<1500 g) (N = 250) and term-born individuals (N = 230) and their parents (VP or VLBW: N = 219; term: N = 227) from birth to adulthood. Parental quality of life was evaluated with the World Health Organization Quality of Life assessment and the Satisfaction with Life questionnaire when their offspring were adults (mean age 27.3 years, 95% confidence interval [CI]: 27.2 to 27.3). Childhood standard assessments of VP or VLBW and term offspring included neurosensory disability, academic achievement, mental health, and parent-child and peer relationships. RESULTS: Overall quality of life of parents of VP or VLBW adults was found to be comparable to parents of term individuals (P > .05). Parental quality of life was not predicted by their children being born VP or VLBW, experiencing disability, academic achievement, or the parent-child relationship in childhood but by their offspring’s mental health (B = 0.15, 95% CI: 0.08 to 0.22) and peer relationships (B = 0.09, 95% CI: 0.02 to 0.16) in childhood. CONCLUSIONS: As a testament to resilience, parents of VP or VLBW adults had quality of life comparable to parents of term adults. Support and interventions to improve mental health and peer relationships in all children are likely to improve parents’ quality of life.