Disrupted developmental organization of the structural connectome in fetuses with corpus callosum agenesis.
Agenesis of the corpus callosum is a model disease for disrupted connectivity of the human brain, in which the pathological formation of interhemispheric fibers results in subtle to severe cognitive deficits. Postnatal studies suggest that the characteristic abnormal pathways in this pathology are compensatory structures that emerge via neural plasticity. We challenge this hypothesis and assume a globally different network organization of the structural interconnections already in the fetal acallosal brain. Twenty fetuses with isolated corpus callosum agenesis with or without associated malformations were enrolled and fiber connectivity among 90 brain regions was assessed using in utero diffusion tensor imaging and streamline tractography. Macroscopic scale connectomes were compared to 20 gestational age-matched normally developing fetuses with multiple granularity of network analysis. Gradually increasing connectivity strength and tract diffusion anisotropy during gestation were dominant in antero-posteriorly running paramedian and antero-laterally running aberrant pathways, and in short-range connections in the temporoparietal regions. In fetuses with associated abnormalities, more diffuse reduction of cortico-cortical and cortico-subcortical connectivity was observed than in cases with isolated callosal agenesis. The global organization of anatomical networks consisted of less segregated nodes in acallosal brains, and hubs of dense connectivity, such as the thalamus and cingulate cortex, showed reduced network centrality. Acallosal fetal brains show a globally altered connectivity network structure compared to normals. Besides the previously described Probst and sigmoid bundles, we revealed a prenatally differently organized macroconnectome, dominated by increased connectivity. These findings provide evidence that abnormal pathways are already present during at early stages of fetal brain development in the majority of cerebral white matter.
Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Computational Imaging Research Lab (CIR) Vienna, Austria. Electronic address: andras.jakab@meduniwien.ac.at.
András
A
Jakab
Department for Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna Austria.
Gregor
G
Kasprian
Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Computational Imaging Research Lab (CIR) Vienna, Austria.
Ernst
E
Schwartz
Center for Anatomy and Cell Biology, Department of Systematic Anatomy, Medical University of Vienna, Vienna, Austria.
Gerlinde Maria
GM
Gruber
Department for Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna Austria.
Christian
C
Mitter
Department for Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna Austria.
Daniela
D
Prayer
Department for Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna Austria.
Veronika
V
Schöpf
Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Computational Imaging Research Lab (CIR) Vienna, Austria; Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, Cambridge, MA, USA.
Georg
G
Langs
D061085:Agenesis of Corpus Callosum / Q000196:embryology / Q000473:pathology*; D001921:Brain / Q000196:embryology / Q000473:pathology*; D063132:Connectome; D056324:Diffusion Tensor Imaging / Q000379:methods*; D005260:Female; D047109:Fetal Development; D005315:Fetal Diseases / Q000473:pathology; D005865:Gestational Age; D006801:Humans; D009415:Nerve Net / Q000196:embryology / Q000473:pathology*; D011247:Pregnancy; D011296:Prenatal Diagnosis
Connectome; Corpus callosum agenesis; Corpus callosum hypogenesis; Diffusion tensor imaging; Fetal brain connectivity; Fetal diffusion MRI; Prenatal development