Comparison of spontaneous brain activity revealed by regional homogeneity in AQP4-IgG neuromyelitis optica-optic neuritis versus MOG-IgG optic neuritis patients: a resting-state functional MRI study

Abstract

Objective: Many previous studies have demonstrated that neuromyelitis optica (NMO) patients have abnormalities of brain anatomy and function. However, differences in spontaneous brain activity between myelin oligodendrocyte glycoprotein (MOG)-IgG ON and aquaporin 4(AQP4)-neuromyelitis optica-optic neuritis (ON) remain unknown. In the current study, we investigated the brain neural homogeneity in MOG-IgG ON versus AQP4-IgG NMO-ON subjects by regional homogeneity (ReHo) method using magnetic resonance imaging (MRI).

Patients and methods: A total of 32 NMO-ON and ON subjects (21 with AQP4-IgG+NMO-ON and 11 with MOG-IgG+ON) and 34 healthy controls (HCs) closely matched for age were recruited, and scans were performed for all subjects. A one-way analysis of variance (ANOVA) was performed to determine the regions in which the ReHo was different across the three groups. NMO-ON and ON subjects were distinguished from HCs by a receiver operating characteristic (ROC) curve. The relationship between the mean ReHo in many brain regions and clinical features in NMO subjects was calculated by Pearson correlation analysis.

Results: Compared with HCs, MOG-IgG+ON subjects had significantly decreased ReHo values in the posterior lobe of the left cerebellum and increased ReHo values in the left inferior frontal gyrus, right prefrontal gyrus, and left precentral/postcentral gyrus. AQP4-IgG+NMO-ON subjects showed higher ReHo values in the left inferior frontal gyrus and right middle temporal/occipital gyrus. Compared with MOG-IgG+ON subjects, AQP4-IgG+NMO-ON subjects had lower ReHo values in the posterior lobe of the right cerebellum. AQP4-Ig+NMO-ON subjects showed higher ReHo values in the left precentral/postcentral gyrus and right superior temporal gyrus.

Conclusion: AQP4-IgG+NMO-ON and MOG-IgG+ON subjects showed abnormal synchronized neuronal activity in many brain regions, which is consistent with deficits in visual, motor, and cognitive function. Furthermore, different patterns of synchronized neuronal activity occurred in the AQP4-IgG+NMO-ON and MOG-IgG+ON.

Keywords: AQP4-IgG; MOG-IgG; functional magnetic resonance imaging; neuromyelitis optica-optic neuritis; regional homogeneity; resting state.

Figure 1

One-sample t-test results. Note: Within-group ReHo maps within the AQP4-IgG+NMO-ON (left) and HCs (middle) and MOG-IgG+ONs (right; P<0.001, FDR corrected). Abbreviations: AQP4, aquaporin-4; HCs, healthy controls; L, left; MOG, myelin oligodendrocyte glycoprotein; NMO, neuromyelitis optica; ON, optic neuritis; R, right; ReHo, regional homogeneity; FDR, false discovery rate.

Figure 2

Spontaneous brain activity in the AQP4-IgG+NMO-ON and HCs groups. Notes: Significant activity differences were observed in the LIFG and RMT/OG. The red or yellow denotes higher ReHo values, and the blue areas indicate lower ReHo values (P<0.01 for multiple comparisons using GRF theory (z >2.3, P<0.01, cluster >40 voxels, AlphaSim corrected) (A and B). The mean values of altered ReHo values between the AQP4-IgG+NMO-ON and HC groups (C). Abbreviations: AQP4, aquaporin-4; GRF, Gaussian random field; HCs, healthy controls; L, left; LIFG, left inferior frontal gyrus; NMO, neuromyelitis optica; ON, optic neuritis; R, right; ReHo, regional homogeneity; RMT/OG, right middle temporal/occipital gyrus.

Figure 3

Spontaneous brain activity in the AQP4-IgG+NMO-ON and MOG-lgG+ON groups. Notes: Significant activity differences were observed in the RCPL, LPreCG/PostCG, and RSTG. The red or yellow denotes higher ReHo values, and the blue areas indicate lower ReHo values (P<0.01 for multiple comparisons using GRF theory (z >2.3, P<0.01, cluster >40 voxels, AlphaSim corrected) (A and B). The mean values of altered ReHo values between the AQP4-IgG+NMO-ON and MOG-lgG+ON groups (C). Abbreviations: AQP4, aquaporin-4; GRF, Gaussian random field; L, left; LPreCG/PostCG, left precentral/postcentral gyrus; MOG, myelin oligodendrocyte glycoprotein; NMO, neuromyelitis optica; ON, optic neuritis; R, right; RCPL, right cerebellum posterior lobe; ReHo, regional homogeneity; RSTG, right superior temporal gyrus.

Figure 4

Spontaneous brain activity in the MOG-IgG+ON and HCs groups. Notes: Significant activity differences were observed in the LCPL, LIFG, RPFG and LPreCG/PostCG. The red or yellow denotes higher ReHo values, and the blue areas indicate lower ReHo values (P<0.01 for multiple comparisons using GRF theory (z >2.3, P<0.01, cluster >40 voxels, AlphaSim corrected) (A and B). The mean values of altered ReHo values between the MOG-IgG+ON and HCs groups (C). Abbreviations: GRF, Gaussian random field; HCs, healthy controls; L, left; LCPL, left cerebellum posterior lobe; LIFG, left inferior frontal gyrus; LPreCG/PostCG, left precentral/postcentral gyrus; MOG, myelin oligodendrocyte glycoprotein; NMO, neuromyelitis optica; ON, optic neuritis; R, right; ReHo, regional homogeneity; RPFG, right prefrontal gyrus.

Figure 5

ROC curve analysis of the mean ReHo values for altered brain regions. Notes: (A) ROC curve: AQP4-IgG+NMO-ON > HCs, for LIFG 0.780 (P=0.002; 95% CI: 0.639–0.921); (B) ROC curve: AQP4-IgG+NMO-ON < HCs, for RMT/OG 0.795 (P<0.001; 95% CI: 0.658–0.932); (C) ROC curve: AQP4-IgG+NMO-ON > MOG-lgG+ON, for RCPL 0.835 (P=0.008; 95% CI: 0.669–1.000); (D) ROC curve: AQP4-IgG+NMO-ON < MOG-IgG+ON, for LPreCG/PostCG 0.913 (P<0.001; 95% CI: 0.669–1.000) and RSTG 0.935 (P<0.001; 95% CI: 0.669–1.000); (E) ROC curve: MOG-IgG+ON < HCs, for LCPL 0.884 (P=0.002; 95% CI: 0.733–1.000); (F) ROC curve: MOG-IgG+ON > HCs, for LIFG 0.925 (P<0.001; 95% CI: 0.803–1.000), RPFG 0.869 (P<0.001; 95% CI: 0.763–0.975), and LPreCG/PostCG 0.872 (P<0.001; 95% CI: 0.732–1.000). Abbreviations: AUC, area under the curve; AQP4, aquaporin-4; HCs, healthy controls; LCPL, left cerebellum posterior lobe; LIFG, left inferior frontal gyrus; LPreCG/PostCG, left precentral/postcentral gyrus; MOG, myelin oligodendrocyte glycoprotein; NMO, neuromyelitis optica; ON, optic neuritis; RCPL, right cerebellum posterior lobe; ReHo, regional homogeneity; RMT/OG, right middle temporal/occipital gyrus; ROC, receiver operating characteristic; RPFG, right prefrontal gyrus; RSTG, right superior temporal gyrus.