Cortical topological network changes following optic neuritis

Abstract

Objective: To differentiate between visual cortical network topology changes following optic neuritis (ON) stemming from different inflammatory disease types, we used mathematical graph theory-based tools to analyze functional imaging data.

Methods: Sixty-two patients were recruited into this cross-sectional study, 23 of whom had neuromyelitis optica spectrum disorder (NMOSD) with ON, 18 with clinically isolated syndrome (CIS)-ON, and 21 with other CIS episodes. Twenty-six healthy controls (HCs) were also recruited. All participants underwent resting-state functional MRI. Visual networks were defined using 50 visual regions of interest. Analysis included graph theory metrics, including degree, density, modularity, and local and global efficiency.

Results: Visual network density shows decreased connectivity in all patient groups compared with controls. A higher degree of connections is seen in both ON groups (CIS and NMOSD) compared with the the non-ON group. This pattern is most pronounced in dorsal-lateral regions. Information transfer efficiency and modularity were reduced in both CIS groups, but not in the NMOSD group, compared with the HC group.

Conclusions: Visual network density appears affected by the neurologic deficit sustained (ON), and connectivity changes are more evident in dorsal-lateral regions. Efficiency and modularity appear to be associated with the specific disease type (CIS vs NMOSD). Thus, topological cortical changes in the visual system are associated with the type of neurologic deficit within the limits set on them by the underlying pathophysiology. We suggest that cortical patterns of activity should be considered in the outcome of the patients despite the localized nature of ON.

Figure 1. Visualization of the translation process from atlas to brain network

(A) Original Wang et al. atlas as transformed into BrainVoyager. (B) Creating thresholded and binarized matrices representing all the connections in both hemispheres. (C) A visual network graph representation (healthy control group).

Figure 2. Regions of interest (ROIs) used

(A) Visual network ROIs, color coded according to classification in Wang et al.—ventral-temporal (red), dorsal-lateral (blue), and parietal-frontal (green). (B) Motor network ROIs. Visualization created using Xia M, et al. d = dorsal; FEF = frontal eye field; hMT = human middle temporal region; hV4 = human visual region V4; IFG = inferior frontal gyrus; IPS = intraparietal sulcus; LO = lateral occipital cortex; M1 = primary motor cortex; MST = medial superior temporal area; PO = pars opercularis; PT = pars triangularis; SMA = supplementary motor area; SPL = superior parietal lobule; v = ventral; VO = ventral occipital cortex; V1 = primary visual cortex; V2 = secondary visual cortex; V3 = visual area V3.

Figure 3. Visualization of the visual system for the 4 subject groups

Considered at correlation threshold r = 0.5, shown in the coronal (back view, top), sagittal (lateral left hemisphere view, middle), and axial (dorsal view, bottom) planes. Nodes (regions of interest) are color coded according to their classification in Wang et al.—ventral-temporal (red), dorsal-lateral (blue), and parietal-frontal (green). The size of nodes reflects the relative degree of a given region in the network. Disconnected regions are presented using an arbitrarily selected size for visualization purposes. Visualization created using reference 55. CIS = clinically isolated syndrome; NMOSD = neuromyelitis optica spectrum disorder; nON = nonoptic neuritis; ON = optic neuritis.

Figure 4. Average degree of all 4 subject groups for selected regions of the 3 region subdivisions

HCs in blue, NMOSD in purple, CIS-ON in red, and CIS-nON in orange. (A) hMT (dorsal-lateral subdivision); (B) VO1 (ventral-temporal subdivision); (C) FEF (frontal eye field, parietal-frontal subdivision). *Significantly different than HC. CIS = clinically isolated syndrome; HC = healthy control; hMT = human middle temporal region; NMOSD = neuromyelitis optica spectrum disorder; nON = nonoptic neuritis; ON = optic neuritis.

Figure 5. Segregation and integration metrics for all 4 subject groups

HCs in blue, NMOSD in purple, CIS-ON in red, and CIS-nON in orange. (A) Modularity; (B) harmonized mean of characteristic path length; (C) global efficiency. *Significantly different than HC; **Significantly different than NMOSD. CIS = clinically isolated syndrome; HC = healthy control; NMOSD = neuromyelitis optica spectrum disorder; nON = nonoptic neuritis; ON = optic neuritis.