Reduced Functional and Anatomic Interhemispheric Homotopic Connectivity in Primary Open-Angle Glaucoma: A Combined Resting State-fMRI and DTI Study.

Purpose To investigate if abnormal interhemispheric homotopic functional connectivity were accompanied by corresponding anatomic connectivity changes in primary open-angle glaucoma (POAG) patients, and to relate connectivity changes with retinal nerve fiber layer (RNFL) thickness and ganglion cell complex (GCC) thickness. Methods Resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI) were performed in 16 POAG patients and 19 healthy controls. Indices of interhemispheric homotopic functional connectivity and the underlying anatomic connectivity changes were derived with voxel-base whole-brain voxel-mirrored homotopic connectivity (VMHC) analyses and VMHC-guided probabilistic tractography. Pearson correlation analyses were used to explore the correlations between interhemispheric homotopic functional connectivity changes and anatomic connectivity alterations, and RNFL and GCC thickness. Results Reduced VMHC values between bilateral homotopic cortical areas located in Brodmann area (BA)17, BA18, and BA19. Decreased anatomic connectivity connecting bilateral visual cortical areas inside BA17 and BA18 were observed in POAG patients. Furthermore, positive correlations between average RNFL thickness and reduced VMHC values of BA17 (r = 0.572, P = 0.021)/BA18 (r = 0.600, P = 0.014)/BA19 (r = 0.550, P = 0.027) are found using Pearson correlation analyses. Conclusions Combinations of interhemispheric homotopic functional connectivity and anatomic connectivity changes may help to elucidate the mechanism of interhemispheric synchronization injury in POAG patients. Reduced VMHC values positively correlate with glaucomatous changes of RNFL thickness, which strengthens the hypothesis that POAG affects the visual cortex using a novel functional MRI characteristic.

[1]  N. De Stefano,et al.  Diffuse brain damage in normal tension glaucoma , 2018, Human brain mapping.

[2]  L. Levin,et al.  Glaucoma and the brain: Trans-synaptic degeneration, structural change, and implications for neuroprotection. , 2017, Survey of ophthalmology.

[3]  Pete A. Williams,et al.  Vitamin B3 modulates mitochondrial vulnerability and prevents glaucoma in aged mice , 2017, Science.

[4]  N. De Stefano,et al.  Early changes of brain connectivity in primary open angle glaucoma , 2016, Human brain mapping.

[5]  Laura Crawley,et al.  Glaucoma: the retina and beyond , 2016, Acta Neuropathologica.

[6]  Peng Zhou,et al.  Abnormal interhemispheric resting-state functional connectivity in primary open-angle glaucoma , 2016, 2016 38th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC).

[7]  Yufeng Zang,et al.  DPABI: Data Processing & Analysis for (Resting-State) Brain Imaging , 2016, Neuroinformatics.

[8]  Feng Liu,et al.  Decreased interhemispheric functional connectivity in insula and angular gyrus/supramarginal gyrus: Significant findings in first-episode, drug-naive somatization disorder , 2016, Psychiatry Research: Neuroimaging.

[9]  Huiguang He,et al.  Graph theoretical analysis reveals the reorganization of the brain network pattern in primary open angle glaucoma patients , 2016, European Radiology.

[10]  Peng Zhang,et al.  Selective reduction of fMRI responses to transient achromatic stimuli in the magnocellular layers of the LGN and the superficial layer of the SC of early glaucoma patients , 2016, Human brain mapping.

[11]  Huiguang He,et al.  Structural brain alterations in primary open angle glaucoma: a 3T MRI study , 2016, Scientific Reports.

[12]  S. Mansberger,et al.  Primary Open-Angle Glaucoma Preferred Practice Pattern(®) Guidelines. , 2016, Ophthalmology.

[13]  Bernhard A. Sabel,et al.  Disturbed temporal dynamics of brain synchronization in vision loss , 2015, Cortex.

[14]  Qing X. Yang,et al.  Interhemispheric Functional and Structural Disconnection in Alzheimer’s Disease: A Combined Resting-State fMRI and DTI Study , 2015, PloS one.

[15]  Ted Maddess,et al.  Refined Frequency Doubling Perimetry Analysis Reaffirms Central Nervous System Control of Chronic Glaucomatous Neurodegeneration. , 2015, Translational vision science & technology.

[16]  Jie Tian,et al.  Altered amplitude of low-frequency fluctuation in primary open-angle glaucoma: a resting-state FMRI study. , 2014, Investigative ophthalmology & visual science.

[17]  Jian Wang,et al.  Decreased interhemispheric functional connectivity in subtypes of Parkinson’s disease , 2015, Journal of Neurology.

[18]  N. De Stefano,et al.  Structural and Functional Brain Changes beyond Visual System in Patients with Advanced Glaucoma , 2014, PloS one.

[19]  Ted Maddess,et al.  Refined Data Analysis Provides Clinical Evidence for Central Nervous System Control of Chronic Glaucomatous Neurodegeneration. , 2014, Translational vision science & technology.

[20]  Dongrong Xu,et al.  Resting‐state functional MRI: Functional connectivity analysis of the visual cortex in primary open‐angle glaucoma patients , 2013, Human brain mapping.

[21]  S. John,et al.  Intrinsic axonal degeneration pathways are critical for glaucomatous damage , 2013, Experimental Neurology.

[22]  Q. Gong,et al.  Structural brain abnormalities in patients with primary open-angle glaucoma: a study with 3T MR imaging. , 2013, Investigative ophthalmology & visual science.

[23]  D. Yin,et al.  Whole-brain voxel-based analysis of diffusion tensor MRI parameters in patients with primary open angle glaucoma and correlation with clinical glaucoma stage , 2013, Neuroradiology.

[24]  D. Javitt,et al.  Decreased interhemispheric coordination in schizophrenia: A resting state fMRI study , 2012, Schizophrenia Research.

[25]  J. Jonas,et al.  Anterior visual pathway assessment by magnetic resonance imaging in normal‐pressure glaucoma , 2012, Acta ophthalmologica.

[26]  David J. Calkins,et al.  The cell and molecular biology of glaucoma: axonopathy and the brain. , 2012, Investigative ophthalmology & visual science.

[27]  J. Crowston,et al.  Definition of glaucoma: clinical and experimental concepts , 2012, Clinical & experimental ophthalmology.

[28]  L. Astrakas,et al.  Voxel-Based Morphometry and Diffusion Tensor Imaging of the Optic Pathway in Primary Open-Angle Glaucoma: A Preliminary Study , 2012, American Journal of Neuroradiology.

[29]  Daniel P. Kennedy,et al.  Intact Bilateral Resting-State Networks in the Absence of the Corpus Callosum , 2011, The Journal of Neuroscience.

[30]  Alan C. Evans,et al.  Growing Together and Growing Apart: Regional and Sex Differences in the Lifespan Developmental Trajectories of Functional Homotopy , 2010, The Journal of Neuroscience.

[31]  Bo Wang,et al.  Functional MRI signal changes in primary visual cortex corresponding to the central normal visual field of patients with primary open-angle glaucoma. , 2010, Investigative ophthalmology & visual science.

[32]  A. Flanders Optic Nerve and Optic Radiation Neurodegeneration in Patients with Glaucoma: In Vivo Analysis with 3-T Diffusion-Tensor MR Imaging , 2010 .

[33]  D. Margulies,et al.  Regional Variation in Interhemispheric Coordination of Intrinsic Hemodynamic Fluctuations , 2008, The Journal of Neuroscience.

[34]  B. Biswal,et al.  Functional connectivity of human striatum: a resting state FMRI study. , 2008, Cerebral cortex.

[35]  N. Gupta,et al.  Atrophy of the lateral geniculate nucleus in human glaucoma detected by magnetic resonance imaging , 2008, British Journal of Ophthalmology.

[36]  J. Piltz-seymour,et al.  Long-term survival of central visual field in end-stage glaucoma. , 2008, Ophthalmology.

[37]  Roberta McKean-Cowdin,et al.  Impact of visual field loss on health-related quality of life in glaucoma: the Los Angeles Latino Eye Study. , 2008, Ophthalmology.

[38]  Edward T. Bullmore,et al.  A simple view of the brain through a frequency-specific functional connectivity measure , 2008, NeuroImage.

[39]  M. Fox,et al.  Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging , 2007, Nature Reviews Neuroscience.

[40]  Mark W. Woolrich,et al.  Probabilistic diffusion tractography with multiple fibre orientations: What can we gain? , 2007, NeuroImage.

[41]  S. Rombouts,et al.  Consistent resting-state networks across healthy subjects , 2006, Proceedings of the National Academy of Sciences.

[42]  H. Quigley,et al.  The number of people with glaucoma worldwide in 2010 and 2020 , 2006, British Journal of Ophthalmology.

[43]  S. Tobimatsu,et al.  Interhemispheric functional synchronization at the first step of visual information processing in humans , 2004, Clinical Neurophysiology.

[44]  D. Badcock,et al.  Psychophysical measurement of neural adaptation abnormalities in magnocellular and parvocellular pathways in glaucoma. , 2004, Investigative ophthalmology & visual science.

[45]  P. Kaufman,et al.  Loss of neurons in magnocellular and parvocellular layers of the lateral geniculate nucleus in glaucoma. , 2000, Archives of ophthalmology.

[46]  R S Harwerth,et al.  Ganglion cell losses underlying visual field defects from experimental glaucoma. , 1999, Investigative ophthalmology & visual science.

[47]  H. Quigley Number of people with glaucoma worldwide. , 1996, The British journal of ophthalmology.

[48]  E. Hedley‐Whyte,et al.  Lateral geniculate nucleus in glaucoma. , 1993, American journal of ophthalmology.

[49]  H Goldmann,et al.  Open-angle glaucoma. , 1972, The British journal of ophthalmology.

[50]  W M Cowan,et al.  Transneuronal cell degeneration in the lateral geniculate nucleus of the macaque monkey. , 1960, Journal of anatomy.

[51]  F. Goldby A NOTE ON TRANSNEURONAL ATROPHY IN THE HUMAN LATERAL GENICULATE BODY , 1957, Journal of neurology, neurosurgery, and psychiatry.