Investigations On Primary Open Angle Glaucoma Patients’ Brain Function In Resting State

BackgroundPrimary open angle glaucoma (POAG), a neurodegenerative optic disease, is the leading cause of irreversible blindness in the world. Clinical features include optic nerve rim loss, retinal nerve fiber damage and visual field defect. According to the epidemiology, the population of POAG patients would be increased to60million at2020, which is a major public health problem. The risk of glaucomatous optic neuropathy increases with multiple risk factors, including elevated intraocular pressure (IOP), age greater than60years, a family history of glaucoma and African race. However, a fundamental understanding of the pathology and mechanism of POAG is still insufficient.Elevated intraocular pressure is the most important risk factor to glaucoma, and reduceing intraocular pressure is the only certain efficient way in glaucoma treatment. The juxta canalicular tissue abnormal is supposed to be related to the elevated intraocular pressure. However, the great fluctuation was more popular observed than elevated intraocular pressure in early stage. Animal researches indicated that intraocular pressure is partly controlled by central nervous system. Long-term stimulation on hypothalamic ventromedial nucleus led to elevated intraocular pressure, aqueous humor generation increased and aqueous humor flowing facility decreased; In addition, stimulation on the locus coeruleus at the same could resist intraocular pressure increases by increasing aqueous humor outflowing facility, although it also increased aqueous generation. Amygdala and hippocampus were also found related to intraocular pressure regulation in animals experiment. Another interesting phenomenon, ciliary nerve (a branch of trigeminal nerve) firing was record when intraocular pressure was increased, and the intraocular pressure reduced after trigeminal ganglia removed, all indicated that a circuit of intraocular pressure regulation might exist.Nowadays, advanced magnetic resonance imaging technology permits visualization of minor changes in the whole brain in vivo. Blood oxygenation level-dependent technique, imaging techniques that detect changes in the concentration of oxygenated and deoxygenated hemoglobin, reflecting neuronal activity. Resting-state functional magnetic resonance imaging can show both spontaneous brain activity and functional connectivity that reflected the endogenous/background neurophysiological processes of the human brain. Taking into account the previous studies and the most current MRI techniques, we applied BOLD technique combined with statistical method of regional homogeneity and functional connectivity to identify the possible mechanism of brain changes in POAG Part OneBackground:The main objective of this study was to investigate spontaneous brain activity in patients with POAG using regional homogeneity (ReHo) analysis based on resting state functional magnetic resonance imaging (rs-fMRI).Methods:Thirty-nine POAG patients and forty-one age-and gender-matched healthy controls were finally included in the study. ReHo values were used to evaluate spontaneous brain activity and whole brain voxel-wise analysis of ReHo was carried out to detect differences by region in spontaneous brain activity between groups. SPSS for Windows20.0. carries out statistical analysis.Results:Compared to controls, POAG patients showed increased ReHo in the right dorsal anterior cingulated cortex, the bilateral medial frontal gyrus and the right cerebellar anterior lobe, and decreased ReHo in the bilateral calcarine, bilateral precuneus gryus, bilateral pre/postcentral gyrus, left inferior parietal lobule and left cerebellum posterior lobe. A multiple linear regression analysis was performed to explore the relationships between clinical measures and ReHo by region showed significant group differences in the POAG group. Negative correlations were found between age and the ReHo values of the superior frontal gyrus (r=-0.323, p=0.045), left calcarine (r=-0.357, p=0.026) and inferior parietal lobule (r=-0.362, p=0.024). A negative correlation was found between the ReHo values of the left precuneus and the cumulative mean defect (r=-0.400, p=0.012).Conclusion:POAG was associated with abnormal brain spontaneous activity in some brain regions and such changed regional activity may be associated with clinical parameters. Abnormal spontaneous brain activity may play a role in POAG initiation and progression. Part TwoObjective:The main objective of this study was to investigate functional connectivity (FC) in patients with POAG using FC analysis based on resting state functional magnetic resonance imaging (rs-fMRI).Methods:Twenty-one POAG patients and Twenty-one age-and gender-matched healthy controls were finally included in the study. FC was used to evaluate functional connectivity, ROI-wise analysis were carried out to detect FC differences between groups.Results:Compared to controls:POAG patients showed decreased strength functional connectivity between left anterior medial prefrontal cortex and left posterior cingulate cortex (t=2.768,p=0.009), left posterior cingulate cortex and bilateral dorsal-medial prefrontal cortex (t=2.237, p=0.031), bilateral medial frontal cortex and left parahippocampal cortex (tr=2.439, p=0.019). But no differences between other ROIs in default mode network; POAG patients also showed negative correlation between IOP and functional connectivity of left anterior prefrontal cortex and bilateral dorsomedia prefrontal cortex(r-=-0.46, p=0.036), and functional connectivity of left anterior prefrontal cortex and bilateral ventrosomedia prefrontal cortex(r=-0.441, p=0.045).Conclusion:POAG was associated with abnormal functional connectivity in DMN. Some abnormal functional connectivity was correlated with IOP.