Abnormal spontaneous brain activity in patients with non-arteritic anterior ischemic optic neuropathy detected using functional magnetic resonance imaging

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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 the most common acute optic nerve disorder in people over 50, causing sudden, painless vision loss in one or both eyes. While doctors know it stems from blocked blood vessels feeding the optic nerve, how NAION affects the brain’s broader activity—beyond just the visual system—has long been a mystery. Most prior research used “task-based” fMRI (which measures brain activity during specific tasks like looking at images), but none explored “resting-state” fMRI—a tool that captures brain activity when a person is at rest, revealing intrinsic network changes. To fill this gap, a team of researchers from Beijing University of Chinese Medicine and partner institutions studied NAION patients using resting-state fMRI to uncover hidden brain patterns.

Who Was in the Study?

The study included 31 NAION patients (20 men, 11 women, average age 52.7 years) and 31 healthy controls matched for age and gender. Sixteen patients had one-eye NAION (eight left, eight right), and 15 had two-eye NAION. All patients met strict criteria: no history of hypertension, heart disease, or MRI contraindications (like metal implants or claustrophobia). Both groups underwent comprehensive eye tests: vision checks, intraocular pressure measurements, optical coherence tomography (OCT) to assess retinal nerve fiber layer (RNFL) thickness (a marker of optic nerve damage), and visual field analysis.

How Was the Research Done?

All participants completed a 1.5 Tesla MRI scan (Philips Intera Achieva system) while wearing blinders and earplugs to minimize external stimuli. For resting-state fMRI, they stayed still with eyes open, avoiding focused thoughts. Researchers used two specialized tools—Data Processing Assistant for Resting-State fMRI (DPARSF) and Resting-State fMRI Data Analysis Toolkit (REST)—to process the data:

  1. Preprocessing: They removed the first 10 scan volumes (to account for initial signal instability), corrected for head movement, and normalized data to a standard brain template (MNI space).
  2. Noise Reduction: They filtered out low-frequency drift (slow signal changes) and high-frequency noise from breathing/heartbeats, focusing on the 0.01–0.08 Hz range (where resting-state brain activity occurs).
  3. ALFF Analysis: They calculated “amplitude of low-frequency fluctuation (ALFF)” for each brain region—a key metric of how active a region is during rest.

What Did They Find?

Compared to healthy controls, NAION patients had:

  • Lower ALFF (less activity): In the right insula (a region linked to emotion and sensory processing), right inferior frontal gyrus (involved in decision-making and audiovisual integration), and both middle frontal gyri (part of the brain’s “default mode network,” or DMN).
  • Higher ALFF (more activity): In the right precuneus (a DMN region critical for spatial awareness and memory).

Crucially, right middle frontal gyrus activity correlated with right RNFL thickness (r=0.42, p=0.02). This means patients with thicker RNFL (less optic nerve damage) had more activity in this brain region—linking eye health directly to brain function.

What Does This Mean for NAION?

The DMN is a core brain network active during rest, governing self-reflection, memory, and spatial awareness. It includes the middle frontal gyrus, precuneus, and insula—all regions altered in NAION patients. Here’s what the changes suggest:

  1. Lower Middle Frontal Gyrus Activity: This region helps with “self-relevant” thinking (e.g., imagining future events). Reduced activity may reflect DMN damage from NAION, potentially affecting cognition or mood.
  2. Higher Precuneus Activity: The precuneus boosts spatial vision and awareness. Increased activity here could be the brain’s way of compensating for vision loss—enhancing spatial processing to make up for damaged optic nerves.
  3. RNFL Link: The correlation between right middle frontal gyrus activity and right RNFL thickness offers a new biomarker: tracking this brain region could help doctors assess NAION severity or monitor recovery.

Why This Study Matters

Prior research on eye diseases like glaucoma has shown DMN changes, but this is one of the first studies to link NAION to spontaneous brain activity. The findings suggest NAION isn’t just an eye problem—it disrupts the brain’s “hub” network (the DMN), with ripple effects on cognition and spatial awareness. For patients, this could explain why some NAION sufferers report “brain fog” or difficulty with spatial tasks—symptoms beyond just vision loss.

The team emphasizes that more research is needed to confirm these links, but the results provide a critical first step toward understanding NAION’s full impact on the brain.

Patient Consent and Funding

All patients provided written consent for their data to be used in the study. The work was funded by the Basic Scientific Research Program from Beijing University of Chinese Medicine (2015-JYB-JSMS107) and the Capital Characteristic Clinical Project (Z171100001017206).

Original study by Peng-De Guo, Peng-Bo Zhao, Han Lv, et al., published in the Chinese Medical Journal (2019). doi:10.1097/CM9.0000000000000134

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