A cross-etiologic study: altered network integration and modularity in newborns with severe diseases
Poster No:
393
Submission Type:
Abstract Submission
Authors:
Anna Speckert1,2,3,4, Kelly Payette5, Walter Knirsch1,6,7, Michael Von Rhein8,4, Cornelia Hagmann9,10,6, Patrice Grehten11,10,6,7, Nicole Ochseinbein-Kölble11,12,1, Raimund Kottke11,10,6,7, Giancarlo Natalucci13,14,1, Ueli Moehrlen1,15,11,10, Lucca Mazzone15,11,10,6, Martin Meuli1,11, Beth Padden10,16,6, Spina bifida study group Zurich study group Zurich17, Beatrice Latal18,4,1, Andras Jakab1,2,4,3
Institutions:
1University of Zurich, Zurich, Switzerland, 2Neuroscience Center Zurich, University of Zurich, Zurich, Switzerland, 3Center for MR Research, University Children's Hospital Zurich, Zurich, Switzerland, 4URPP Adaptive Brain Circuits in Development and Learning, University of Zurich, Zurich, Switzerland, 5King's College London, London, UK, 6Children’s Research Center, University Children’s Hospital Zurich, Zurich, Switzerland, 7Department of Diagnostic Imaging, University Children’s Hospital Zurich, Zurich, Switzerland, 8Child Development Center, University Children’s Hospital Zurich, Zurich, Switzerland, 9Department of Neonatology, University Children’s Hospital Zurich, Zurich, Switzerland, 10Zurich Center for Spina Bifida, University Children’s Hospital Zurich, Zurich, Switzerland, 11The Zurich Center for Fetal Diagnosis and Therapy, Zurich, Switzerland, 12Department of Obstetrics, University Hospital of Zurich, Zurich, Switzerland, 13FLRF Center for Neurodevelopment, Growth and Nutrition of the Newborn, Zurich, Switzerland, 14NGM Research Center, University Hospital Zurich, Zurich, Switzerland, 15Department for Pediatric Surgery, University Children's Hospital Zurich, Zurich, Switzerland, 16Division of Pediatric Rehabilitation, University Children’s Hospital Zurich, Zurich, Switzerland, 17Spina Bifida Study Group Zurich, Zurich, Switzerland, 18Child Development Centre, University Children's Hospital Zurich, Zurich, Switzerland
First Author:
Anna Speckert
University of Zurich|Neuroscience Center Zurich, University of Zurich|Center for MR Research, University Children's Hospital Zurich|URPP Adaptive Brain Circuits in Development and Learning, University of Zurich
Zurich, Switzerland|Zurich, Switzerland|Zurich, Switzerland|Zurich, Switzerland
University of Zurich|Neuroscience Center Zurich, University of Zurich|Center for MR Research, University Children's Hospital Zurich|URPP Adaptive Brain Circuits in Development and Learning, University of Zurich
Zurich, Switzerland|Zurich, Switzerland|Zurich, Switzerland|Zurich, Switzerland
Co-Author(s):
Walter Knirsch
University of Zurich|Children’s Research Center, University Children’s Hospital Zurich|Department of Diagnostic Imaging, University Children’s Hospital Zurich
Zurich, Switzerland|Zurich, Switzerland|Zurich, Switzerland
University of Zurich|Children’s Research Center, University Children’s Hospital Zurich|Department of Diagnostic Imaging, University Children’s Hospital Zurich
Zurich, Switzerland|Zurich, Switzerland|Zurich, Switzerland
Michael Von Rhein
Child Development Center, University Children’s Hospital Zurich|URPP Adaptive Brain Circuits in Development and Learning, University of Zurich
Zurich, Switzerland|Zurich, Switzerland
Child Development Center, University Children’s Hospital Zurich|URPP Adaptive Brain Circuits in Development and Learning, University of Zurich
Zurich, Switzerland|Zurich, Switzerland
Cornelia Hagmann
Department of Neonatology, University Children’s Hospital Zurich|Zurich Center for Spina Bifida, University Children’s Hospital Zurich|Children’s Research Center, University Children’s Hospital Zurich
Zurich, Switzerland|Zurich, Switzerland|Zurich, Switzerland
Department of Neonatology, University Children’s Hospital Zurich|Zurich Center for Spina Bifida, University Children’s Hospital Zurich|Children’s Research Center, University Children’s Hospital Zurich
Zurich, Switzerland|Zurich, Switzerland|Zurich, Switzerland
Patrice Grehten
The Zurich Center for Fetal Diagnosis and Therapy|Zurich Center for Spina Bifida, University Children’s Hospital Zurich|Children’s Research Center, University Children’s Hospital Zurich|Department of Diagnostic Imaging, University Children’s Hospital Zurich
Zurich, Switzerland|Zurich, Switzerland|Zurich, Switzerland|Zurich, Switzerland
The Zurich Center for Fetal Diagnosis and Therapy|Zurich Center for Spina Bifida, University Children’s Hospital Zurich|Children’s Research Center, University Children’s Hospital Zurich|Department of Diagnostic Imaging, University Children’s Hospital Zurich
Zurich, Switzerland|Zurich, Switzerland|Zurich, Switzerland|Zurich, Switzerland
Nicole Ochseinbein-Kölble
The Zurich Center for Fetal Diagnosis and Therapy|Department of Obstetrics, University Hospital of Zurich|University of Zurich
Zurich, Switzerland|Zurich, Switzerland|Zurich, Switzerland
The Zurich Center for Fetal Diagnosis and Therapy|Department of Obstetrics, University Hospital of Zurich|University of Zurich
Zurich, Switzerland|Zurich, Switzerland|Zurich, Switzerland
Raimund Kottke
The Zurich Center for Fetal Diagnosis and Therapy|Zurich Center for Spina Bifida, University Children’s Hospital Zurich|Children’s Research Center, University Children’s Hospital Zurich|Department of Diagnostic Imaging, University Children’s Hospital Zurich
Zurich, Switzerland|Zurich, Switzerland|Zurich, Switzerland|Zurich, Switzerland
The Zurich Center for Fetal Diagnosis and Therapy|Zurich Center for Spina Bifida, University Children’s Hospital Zurich|Children’s Research Center, University Children’s Hospital Zurich|Department of Diagnostic Imaging, University Children’s Hospital Zurich
Zurich, Switzerland|Zurich, Switzerland|Zurich, Switzerland|Zurich, Switzerland
Giancarlo Natalucci
FLRF Center for Neurodevelopment, Growth and Nutrition of the Newborn|NGM Research Center, University Hospital Zurich|University of Zurich
Zurich, Switzerland|Zurich, Switzerland|Zurich, Switzerland
FLRF Center for Neurodevelopment, Growth and Nutrition of the Newborn|NGM Research Center, University Hospital Zurich|University of Zurich
Zurich, Switzerland|Zurich, Switzerland|Zurich, Switzerland
Ueli Moehrlen
University of Zurich|Department for Pediatric Surgery, University Children's Hospital Zurich|The Zurich Center for Fetal Diagnosis and Therapy|Zurich Center for Spina Bifida, University Children’s Hospital Zurich
Zurich, Switzerland|Zurich, Switzerland|Zurich, Switzerland|Zurich, Switzerland
University of Zurich|Department for Pediatric Surgery, University Children's Hospital Zurich|The Zurich Center for Fetal Diagnosis and Therapy|Zurich Center for Spina Bifida, University Children’s Hospital Zurich
Zurich, Switzerland|Zurich, Switzerland|Zurich, Switzerland|Zurich, Switzerland
Lucca Mazzone
Department for Pediatric Surgery, University Children's Hospital Zurich|The Zurich Center for Fetal Diagnosis and Therapy|Zurich Center for Spina Bifida, University Children’s Hospital Zurich|Children’s Research Center, University Children’s Hospital Zurich
Zurich, Switzerland|Zurich, Switzerland|Zurich, Switzerland|Zurich, Switzerland
Department for Pediatric Surgery, University Children's Hospital Zurich|The Zurich Center for Fetal Diagnosis and Therapy|Zurich Center for Spina Bifida, University Children’s Hospital Zurich|Children’s Research Center, University Children’s Hospital Zurich
Zurich, Switzerland|Zurich, Switzerland|Zurich, Switzerland|Zurich, Switzerland
Martin Meuli
University of Zurich|The Zurich Center for Fetal Diagnosis and Therapy
Zurich, Switzerland|Zurich, Switzerland
University of Zurich|The Zurich Center for Fetal Diagnosis and Therapy
Zurich, Switzerland|Zurich, Switzerland
Beth Padden
Zurich Center for Spina Bifida, University Children’s Hospital Zurich|Division of Pediatric Rehabilitation, University Children’s Hospital Zurich|Children’s Research Center, University Children’s Hospital Zurich
Zurich, Switzerland|Zurich, Switzerland|Zurich, Switzerland
Zurich Center for Spina Bifida, University Children’s Hospital Zurich|Division of Pediatric Rehabilitation, University Children’s Hospital Zurich|Children’s Research Center, University Children’s Hospital Zurich
Zurich, Switzerland|Zurich, Switzerland|Zurich, Switzerland
Spina bifida study group Zurich study group Zurich
Spina Bifida Study Group Zurich
Zurich, Switzerland
Spina Bifida Study Group Zurich
Zurich, Switzerland
Beatrice Latal
Child Development Centre, University Children's Hospital Zurich|URPP Adaptive Brain Circuits in Development and Learning, University of Zurich|University of Zurich
Zurich, Switzerland|Zurich, Switzerland|Zurich, Switzerland
Child Development Centre, University Children's Hospital Zurich|URPP Adaptive Brain Circuits in Development and Learning, University of Zurich|University of Zurich
Zurich, Switzerland|Zurich, Switzerland|Zurich, Switzerland
Andras Jakab
University of Zurich|Neuroscience Center Zurich, University of Zurich|URPP Adaptive Brain Circuits in Development and Learning, University of Zurich|Center for MR Research, University Children's Hospital Zurich
Zurich, Switzerland|Zurich, Switzerland|Zurich, Switzerland|Zurich, Switzerland
University of Zurich|Neuroscience Center Zurich, University of Zurich|URPP Adaptive Brain Circuits in Development and Learning, University of Zurich|Center for MR Research, University Children's Hospital Zurich
Zurich, Switzerland|Zurich, Switzerland|Zurich, Switzerland|Zurich, Switzerland
Introduction:
The human brain connectome is characterized by the duality of highly modular structure and efficient integration, supporting information processing (8). Newborns with congenital heart disease (CHD) (5), prematurity (3), or spina bifida (SB) aperta (4) are at risk for altered brain development and developmental delay (DD), which refers to a deviation from expected developmental milestones (6). We hypothesize that in cognitive DD, neural circuitry impairments are reflected by alterations of this connectomic organization. Our study aims to bridge this knowledge gap by using a multi-etiologic neonatal dataset to reveal potential commonalities and distinctions in the structural brain connectome and their associations with DD.
Methods:
We used diffusion MRI (dMRI) on 187 neonates (42 controls, 51 CHDs, 51 preterms, 43 SB aperta). Axial dMRI data acquisition used a pulsed gradient spin-echo echo-planar imaging sequence (TR/TE 3950/90.5 ms, field of view=18 cm, matrix=128×128, slice thickness=3 mm) with 35 diffusion encoding gradient directions at a b-value of 700 s/mm2 and four b=0 images on a 3.0T MRI. The DTI sequence for preterms differed in the number of diffusion directions (21, b=1000 s/mm2). Structural connectomic analysis involved the following steps: denoising, eddy-current with slice-to-volume correction (1) and B1 bias field inhomogeneity correction. Weighted networks were constructed using constrained spherical deconvolution-based probabilistic anatomically constrained tractography from the MRtrix3 Software (7) and the Edinburgh Neonatal Atlas (2). The assessment of connectomic structure included measures of global efficiency, modularity, and rich club coefficient. To facilitate cross-dataset comparisons by normalization, null-network models were utilized by randomizing the network edges while preserving degree-, weight- and strength- distributions (9). The Cognitive Composite Score of the Bayley Scales of Infant and Toddler Development-III was used as outcome measure at 2 years for children born premature and with SB, and at 1 year for the control and CHD children.
Results:
We revealed differences in the connectomic structure of newborns across each of the four groups after visualizing the connectomes in a two-dimensional morphospace defined by network integration and segregation (Fig. 1). Further, ANCOVA analyses, after adjustment for postmenstrual age at scan and gestational age at birth, revealed differences in global efficiency (F(3, 182)=7.66, p<0.0001), modularity (F(3, 182)=16.97, p<0.0001) and mean rich club coefficient (F(3, 182)=3.50, p=0.017) between groups. Post hoc analysis was performed with a Bonferroni adjustment (Fig. 2). The normalized mean global efficiency score was significantly greater in premature babies (-6.44+/-0.94) compared to CHDs (-10.1+/-0.50). Additionally, the mean global efficiency score was higher in SB (-7.89+/-0.38) compared to controls (-9.82+/-0.46), and CHDs, p<0.001. Further, the normalized mean modularity score was significantly greater in CHDs (16.5+/-0.5) compared to SB (13.4+/-0.38) and controls (15.3+/-0.46). SB newborns showed lower mean modularity than controls, p<0.001. Lastly, the normalized mean rich club coefficient was found to be significantly greater in SB (0.55+/-0.18) compared to controls (-0.13+/-0.21). However, in our analysis, we found no significant association between the identified neural connectivity patterns and cognitive outcome scores. This lack of association was true for both the overall study and specific for within group analysis.
·Morphospace with z-normalized scores of modularity and integration (measured by global efficiency) of 42 controls, 51 CHDs, 43 SB aperta and 51 preterms.
·Estimated marginal means of the ANCOVA models after post-hoc test with Bonferroni adjustment. Error bars represent the 95% confidence intervals.
Conclusions:
In this cross-etiologic study, we identified divergent profiles of the structural brain connectome characterized by a deviation from the optimal combination of network integration and segregation. Early cognitive developmental outcomes were not yet associated with alterations in the organization of the connectome. Further work is necessary to find out if longer term cognitive outcomes are determined by such connectomic alterations.
Disorders of the Nervous System:
Neurodevelopmental/ Early Life (eg. ADHD, autism) 1
Lifespan Development:
Early life, Adolescence, Aging
Modeling and Analysis Methods:
Connectivity (eg. functional, effective, structural) 2
Keywords:
Cognition
Congenital
Development
DISORDERS
MRI
PEDIATRIC
Tractography
WHITE MATTER IMAGING - DTI, HARDI, DSI, ETC
Other - connectome; graph theory
1|2Indicates the priority used for review
Provide references using author date format
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4. Lomax-Bream, L. E. (2007), 'The impact of spina bifida on development across the first 3 years', Developmental Neuropsychology, vol. 31, no. 1, pp. 1-20.
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