Abnormal Spontaneous Brain Activity in Patients with Non-Arteritic Anterior Ischemic Optic Neuropathy Detected Using Functional Magnetic Resonance Imaging
Non-arteritic anterior ischemic optic neuropathy (NAION) is a condition characterized by a sudden onset of unilateral painless visual loss and a swollen optic disc. It is the most common form of acute optic neuropathy in individuals over 50 years of age. Despite its prevalence, the pathogenesis of NAION remains unclear, though most histopathological studies suggest that it involves vasculopathic occlusion in the region of the short posterior ciliary arteries. Functional magnetic resonance imaging (fMRI) is a non-invasive technique widely used to measure brain function over time in vivo. While previous research has explored the effects of stimulating the affected eye in NAION patients using task-state fMRI, there has been a lack of investigation into resting-state fMRI (rs-fMRI). This gap in research raises the question of whether regional spontaneous brain changes in NAION are limited to the visual system or extend to other areas of the brain.
To address this question, a study was conducted involving 31 patients with NAION (20 males, 11 females, aged 35 to 79 years, mean age 52.74±11.29 years) and 31 normal controls (NCs) (20 males, 11 females, aged 33 to 66 years, mean age 50.97±8.20 years) matched in age and gender. The patients were treated at Dongfang Hospital, Beijing University of Chinese Medicine between June 2015 and November 2017. Among the NAION patients, 16 exhibited unilateral NAION (eight in the left eye and eight in the right eye), while 15 had bilateral NAION (either sequentially or simultaneously in both eyes). All patients met specific criteria, including sudden, painless, monocular or bilateral visual loss, standardized treatment and evaluation at the hospital, no history of hypertension, coronary artery disease, drug addiction, or sleep disorder, and no contraindications for MRI scans such as claustrophobia or irremovable metal in the body. Both patients and NCs underwent eyesight testing, intraocular pressure measurement, optical coherence tomography (OCT) to measure retinal nerve fiber layer (RNFL) thickness, and visual field analysis.
All participants underwent MRI scans using a 1.5 Tesla Philips Intera Achieva system. High-resolution structural images were obtained using a three-dimensional brain volume technique. Resting-state fMRI was conducted using an echo planar imaging pulse sequence with specific parameters: matrix 64×64, field of view 20 cm x 20 cm, slice thickness 3.6 mm, space between slices 0.72 mm, number of excitations 1, repetition time/echo time 3000/30, flip angle 90°, 35 slices, dynamic scan 100 times, and a total scan time of 5.06 minutes. Participants were instructed to remain motionless with their eyes open and to avoid thinking of anything specific during the scan. Resting-state fMRI data were processed using Data Processing Assistant for Resting-State fMRI (DPARSF) software, based on Statistical Parametric Mapping (SPM8), and the Resting-State fMRI Data Analysis Toolkit (REST). Pre-processing steps included removing the first 10 volumes to account for signal instability, slice timing, and head motion correction. Subjects with head motion exceeding 1.5 mm maximum displacement or rotation motion greater than 1.5° in the x, y, or z-axis were excluded, resulting in the exclusion of four patients. The remaining fMRI series were spatially normalized and coregistered to the standard stereotactic Montreal Neurological Institute (MNI) space. After pre-processing, fMRI images were smoothed with a Gaussian kernel, and temporal bandpass filtering and linear trend removal were performed to eliminate low-frequency drift and physiological noise. Individual amplitude of low-frequency fluctuation (ALFF) maps were generated for each data series.
Statistical analysis was conducted using REST software. Two-sample t-tests were used to compare ALFF values between NAION patients and NCs, with gender, age, and disease duration as covariates. The significance level for multiple comparisons was corrected using a false discovery rate (FDR)-corrected threshold of P<0.05. Results were visualized using Xjview toolbox and REST software. Pearson correlation analyses were performed using SPSS 17.0 software to explore correlations between abnormal ALFF values and clinical parameters.
The study found that, compared to NCs, NAION patients exhibited lower ALFF values in the right insula, right inferior frontal gyrus, and bilateral middle frontal gyrus, but higher ALFF values in the right precuneus. These findings suggest that NAION may lead to dysfunction in the default mode network (DMN), a brain network involved in various cognitive functions. The DMN includes regions such as the medial prefrontal cortex, medial parietal cortex, precuneus, lateral temporal parietal cortex, parahippocampal gyrus, and hippocampal formation. The DMN is active during resting-state conditions and is negatively correlated with functions such as vision, hearing, and somatesthesia. Abnormalities in DMN activity have been observed in other optic neuropathies, such as glaucoma and optic neuritis, suggesting a potential link between optic nerve damage and DMN dysfunction.
The right insula and inferior frontal gyrus are regions involved in audiovisual communication and other cognitive processes. Lower ALFF values in these areas in NAION patients may reflect functional damage. The precuneus, a key component of the DMN, is involved in tasks such as visuospatial imagery, spatial awareness, and consciousness. Increased ALFF values in the right precuneus in NAION patients may indicate compensatory mechanisms to maintain network stability or enhance spatial vision processing. The middle frontal gyrus, another subsystem of the DMN, is involved in self-relevant mental simulation. Lower ALFF values in the bilateral middle frontal gyrus in NAION patients, along with a positive correlation between ALFF values in the right middle frontal gyrus and right RNFL thickness, suggest that NAION may cause significant damage to this region. This correlation also indicates that RNFL thickness could serve as a useful index for understanding the neural mechanisms underlying NAION.
In conclusion, this study revealed abnormalities in spontaneous brain activity in NAION patients, particularly in regions associated with the DMN. The findings suggest that NAION affects the brain’s functional network, with potential implications for understanding the neural mechanisms of the disease. The study highlights the importance of rs-fMRI in uncovering the broader impact of NAION on brain function and provides valuable insights for future research and clinical practice.
doi.org/10.1097/CM9.0000000000000134
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