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. 2022 May 12:16:885770.
doi: 10.3389/fnins.2022.885770. eCollection 2022.

Brain Gray Matter Atrophy and Functional Connectivity Remodeling in Patients With Chronic LHON

Qin Tian  1 , Ling Wang  1 , Yu Zhang  2   3 , Ke Fan  4 , Meng Liang  2   3   5 , Dapeng Shi  1 , Wen Qin  2   3 , Hao Ding  2   3   5
Affiliations

Brain Gray Matter Atrophy and Functional Connectivity Remodeling in Patients With Chronic LHON

Qin Tian et al. Front Neurosci. .

Abstract

Purpose: The aim of this study was to investigate the brain gray matter volume (GMV) and spontaneous functional connectivity (FC) changes in patients with chronic Leber's hereditary optic neuropathy (LHON), and their relations with clinical measures.

Methods: A total of 32 patients with chronic LHON and matched sighted healthy controls (HC) underwent neuro-ophthalmologic examinations and multimodel magnetic resonance imaging (MRI) scans. Voxel-based morphometry (VBM) was used to detect the GMV differences between the LHON and HC. Furthermore, resting-state FC analysis using the VBM-identified clusters as seeds was carried out to detect potential functional reorganization in the LHON. Finally, the associations between the neuroimaging and clinical measures were performed.

Results: The average peripapillary retinal nerve fiber layer (RNFL) thickness of the chronic LHON was significantly thinner (T = -16.421, p < 0.001), and the mean defect of the visual field was significantly higher (T = 11.28, p < 0.001) than the HC. VBM analysis demonstrated a significantly lower GMV of bilateral calcarine gyri (CGs) in the LHON than in the HC (p < 0.05). Moreover, in comparison with the HC, the LHON had significantly lower FC between the centroid of the identified left CG and ipsilateral superior occipital gyrus (SOG) and higher FC between this cluster and the ipsilateral posterior cingulate gyrus (p < 0.05, corrected). Finally, the GMV of the left CG was negatively correlated with the LHON duration (r = -0.535, p = 0.002), and the FC between the left CG and the ipsilateral posterior cingulate gyrus of the LHON was negatively correlated with the average peripapillary RNFL thickness (r = -0.522, p = 0.003).

Conclusion: The atrophied primary visual cortex of the chronic LHON may be caused by transneuronal degeneration following the retinal damage. Moreover, our findings suggest that the functional organization of the atrophied primary visual cortex has been reshaped in the chronic LHON.

Keywords: LHON; functional connectivity (FC); gray matter volume (GMV); reorganization; visual cortex (V1).

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Inter-group differences in gray matter volume (GMV) and white matter volume. (A) The difference in GMV between the LHON and HC was tested using a voxel-wise non-parametric permutation test corrected for age and gender (p < 0.05, TFCE-FWE corrected). Chronic LHON had significantly lower GMV in the bilateral CG than in the HC (cool color). (B) The difference in WMV between the LHON and HC was tested using a voxel-wise non-parametric permutation test corrected for age and gender (p < 0.05, TFCE-FWE corrected). Chronic LHON had significantly lower WMV in the bilateral OR, bilateral OT, and left LGN than in the HC (cool color). Color bar represents the -log(p) value. CG, calcarine gyrus; FWE, family-wise error; GMV, gray matter volume; HC, healthy controls; LGN, lateral geniculate nucleus; LHON, Leber's hereditary optic neuropathy; OR, optic radiation; OT, optic tract; TFCE, threshold-free cluster enhancement; WMV, white matter volume.
Figure 2
Figure 2
Inter-group differences in resting-state functional connectivity. The difference in FC between the chronic LHON and HC was test using a voxel-wise non-parametric permutation test corrected for age and gender (p < 0.05, TFCE-FWE corrected). Color bar represents the -log10(p) value. (A) Seeds (left CG) used to calculate the FC, (B) brain region (left SOG, cool color) having lower FC with the left CG in the chronic LHON, and (C) brain region (left PCC, warm color) having higher FC with the left CG. CG, calcarine gyrus; FC, functional connectivity; FWE, family-wise error; HC, healthy controls; LHON, Leber's hereditary optic neuropathy; PCC, posterior cingulate cortex; SOG, superior occipital gyrus; TFCE, threshold-free cluster enhancement.
Figure 3
Figure 3
Correlation between the neuroimaging findings and clinical measures in the chronic LHON. (A) Spearman correlation coefficient was used to test the association between LHON duration and GMV of left CG, and (B) Pearson correlation coefficient was used to test that between peripapillary RNFL thickness and FC between the left CG and left PCC (p < 0.05, Bonferroni correction). CG, calcarine gyrus; FC, functional connectivity; GMV, gray matter volume; LHON, Leber's hereditary optic neuropathy; PCC, posterior cingulate cortex; RNFL, retinal nerve fiber layer.
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