Gender-specific attention system subnetwork vulnerability in prematurely born children
Elda Fischi-Gomez1,2, Lana Vasung1, Sebastien Urben3,4, Cristina Borradori-Tolsa1, François Lazeyras5, Jean-Philippe Thiran2,6, and Petra Susan Hüppi1

1Division of Development and Growth. Department of Pediatrics, University Hospital of Geneva, Geneva, Switzerland, 2Signal Processing Laboratory 5, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland, 3Child Clinical Neuropsychology Unit, Department of Psychology, University of Geneva, Geneva, Switzerland, 4Research Unit, University Service of Child and Adolescent Psychiatry, Department of Psychiatry, University Hospital of Lausanne (CHUV), Lausanne, Switzerland, 5Department of Radiology and Medical Informatics, Faculty of Medicine, University of Geneva, Geneva, Switzerland, 6Department of Radiology, University Hospital Center (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland


Within preterm-born children, being born male and at a lower gestational age have both been associated with a heightened risk for developmental difficulties. However, in this population little is known about the combined effect and the influence of these risk factors on the structural networks subserving attention and executive. Using a diffusion-based brain connectome approach, in this work we analyze the effect of these two factors in the brain networks of school-age preterm born children and provide evidence of a gender-specific vulnerability in the executive attentional subnetwork.


Children born prematurely are at high risk for long-term abnormal development, including deficits in attentional abilities that persist throughout adolescence [1]. The severity of these cognitive difficulties varies significantly among preterm-born children, with the level of prematurity and sex being the most relevant factors for the determination of their neurodevelopmental outcomes [2,3]. In order to understand the neurostructural correlate of these disabilities, we used a brain connectome approach to analyze the effects of gender and degree of prematurity on the attentional system network related to executive control in school age preterm children. Our results suggest that extreme prematurity, toghether with being born male, differentially affects brain connectivity and development.


To study the structural network subserving attention and executive control in prematurely born children at school age.


We recruited 44 premature born children aged six years old, from the Child Developmental Unit at the University Hospitals of Geneva and Lausanne. All subjects were free from premature-associated brain lesions at term equivalent age. The 6 years-old scans were read as normal by neuroradiologists. Our scanning protocol included: T1-weighted MPRAGE (TR/TE=2500/2.91, TI=1100, res.=1x1x1mm, 256x154) and diffusion-sensitized EPI sequence (30 directions, max bvalue=1000 s/mm2, TR/TE=10200/107, res=1.8x1.8x2 mm) on a Siemens 3T Tim Trio. Children were divided in 4 groups based on GA (extremely preterm (EP) vs very preterm (VPT), < 28 vs ≤ 28 <34.3 weeks GA resp.) and gender (boys vs girls). For each subject we compute the connectivity matrix using the Connectome Mapper Toolkit [4]. We model the structural brain networks as undirected weigthed networks with the nodes being the centroid of each cortical (and subcortical) region of interest (ROI) and the edges the average connection density of all subjects weighted by the individual connection efficacy (mean FA along the bundle connecting the two ROIs). The executive attention subtnetwork (eATN) was defined by selecting the nodes as described by Posner and Petersen [5,6], including the frontoparietal control system and the cingulo-opercular system, bilaterally. As an initial examination of connectivity in the preterm infants brain, we compared the global efficiency of their whole brain networks among groups, as well as the global efficiency of the right and left eATN. The eATN connectivity and its behavior with respect to the overall brain wetwork was examined by disinguishing different types of connections: local connections between peripheral nodes (peripheral), feeder connections between peripheral nodes and the core nodes, i.e. nodes belonging to the eATN (feeders), core connections between nodes belonging to the eATN only (core) and feeder and core connections (core+feeders) (Fig. 1). The strenght of these connections was compared among groups using a ranksum test and correted for multiple comparisons using FDR.


The overall global efficiency showed no significant difference among groups. On the contrary, the global efficiency of the eATN of the right hemisphere was significantly lower when comparing EP boys and girls with VPT boys and girls. Interestingly, VPT boys showed a reduced efficiency on the eATN when compared to VPT girls. For the left eATN, EP boys and girls also showed reduces efficiency when compared to the VPT. EP boys also had smaller efficiency when compared to VPT girls, and most importantly, the subnetwork efficiency was reduced in VPT boys when compared to EP girls. The strength the eATN core, feeders and feeders+core connections was significantly lower in EP boys when compared with girls, independently from their GA. Moreover, EP boys peripherial connections showed also reduced connectivity strength when compared to EP girls.


Petersen and Posner [6] described the frontoparietal control system as a part of the executive attention network. This system enables a moment-to-moment control, responsible for resolving conflicts. Lesions of this system in adulthood (especially of the dorsolateral prefrontal cortex, DLPFC) result in executive control deficits, decision-making, and judgment impairments [7]. Similarly, the impaired executive control abilities in extremely preterm boys have been related to lower cortical densities in the DLPFC [1]. Our analysis corroborates these results and provides evidence of alteration in intrinsic eATN network architecture (core connections) but also of alteration in hemispheric integration of eATN network (connections between eATN and feeders), which are related to extreme prematurity and sex. In addition, having in mind that extreme prematurity has been linked with altered fronto-striatal and frontoparietal connectivity [8], our results further suggest that networks related to executive control are differently affected by the sex and the level of prematurity. In other words, boys and girls are neurologically differentially impacted by these two factors.


The current findings do shed light on a gender-specific vulnerability in the executive attentional subnetwork.


This work was supported by the Center for Biomedical Imaging (CIBM) of the Geneva and Lausanne Universities, the Ecole Polytechnique Fédérale de Lausanne (EPFL) in Switzerland, and the foundations Leenards and Louis-Jeantet, as well as by the Swiss National Science Foundation (33CM30_140334 and 32473B_135817) and Leenards Foundation Grant N° 2667 to P.S.H. We are grateful to the families that took part in the study and the medical staff who participated in the study. We thank Dr.Alessanda Griffa for insightful comments.


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Illustration of the different connections considered in the network analysis. Red circles indicate nodes belonging to the eATN subnetwork and gray circles depict nodes outside this subnetwork. Red lines indicate the connections between nodes inside the eATN (core connections); in gray, the connections between peripherial nodes and green lines indicate the one-jump connections linking peripherial nodes to the core node (feeders).

Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)