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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Neurol. | doi: 10.3389/fneur.2019.01134

Primary open angle Glaucoma is associated with functional brain network reorganization

 Silvia Minosse1*, Francesco Garaci1, 2,  Alessio Martucci3, Simona Lanzafame1,  Francesca Di Giulianio1, Eliseo Picchi1, Massimo Cesareo3, Raffaele Mancino3, Maria Guerrisi1, Chiara Adriana Pistolese1, Roberto Floris1,  Carlo Nucci3 and  Nicola Toschi1, 4
  • 1Department of Biomedicine and Prevention, University of Rome Tor Vergata, Italy
  • 2San Raffaele Cassino, Italy
  • 3Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Italy
  • 4Athinoula A. Martinos Center for Biomedical Imaging, Harvard Medical School, United States

Background: Resting-state functional magnetic resonance imaging (rs-fMRI) is commonly employed to study changes in functional brain connectivity. The recent hypothesis of a brain involvement in primary open angle Glaucoma has sprung interest for neuroimaging studies in this classically ophthalmological pathology.
Object: We explored a putative reorganization of functional brain networks in Glaucomatous patients, and evaluated the potential of functional network disruption indices as biomarkers of disease severity in terms of their relationship to clinical variables as well as select retinal layer thicknesses.
Methods: Nineteen Glaucoma patients and sixteen healthy control subjects (age: 50 – 76, mean 61.0 8.2 years) underwent rs-fMRI examination at 3T. After preprocessing, rs-fMRI time series were parcellated into 116 regions using the Automated Anatomical Labeling atlas and adjacency matrices were computed based on partial correlations. Graph-theoretical measures of integration, segregation and centrality as well as group-wise and subject-wise disruption index estimates (which use regression of graph-theoretical metrics across subjects to quantify overall network changes) were then generated for all subjects. All subjects also underwent Optical-Coherence Tomography (OCT) and visual field index (VFI) quantification. We then examined associations between brain network measures and VFI, as well as thickness of retinal nerve fiber layer (RNFL) and macular ganglion cell layer (MaculaGCL).
Results: In Glaucoma, group-wise disruption indices were negative for all graph theoretical metrics. Also, we found statistically significant group-wise differences in subject-wise disruption indexes in all local metrics. Two brain regions serving as hubs in healthy controls were not present in the Glaucoma group. Instead, three hub regions were present in Glaucoma patients but not in controls. We found significant associations between all disruption indices and VFI, RNFL as well as MaculaGCL. The disruption index based on the clustering coefficient yielded the best discriminative power for differentiating Glaucoma patients from healthy controls (Area Under the ROC curve (AUC) 0.91, sensitivity, 100%; specificity, 78.95%).
Conclusions: Our findings support a possible relationship between functional brain changes and disease severity in Glaucoma, as well as alternative explanations for motor and cognitive symptoms in Glaucoma, possibly pointing towards an inclusion of this pathology in the heterogeneous group of disconnection syndromes.

Keywords: - Resting-state functional magnetic resonance imaging (rs-fMRI), - Open Angle Glaucoma , - Graph Theoretical Measures, - Functional brain networks , - Neurodegenerative diseases

Received: 29 Apr 2019; Accepted: 10 Oct 2019.

Copyright: © 2019 Minosse, Garaci, Martucci, Lanzafame, Di Giulianio, Picchi, Cesareo, Mancino, Guerrisi, Pistolese, Floris, Nucci and Toschi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Mx. Silvia Minosse, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy,