Anatomical Wiring and Functional Networking Changes in the Visual System Following Optic Neuritis

Abstract

Importance: Clinical outcome in multiple sclerosis was suggested to be driven by not only remyelination but also adaptive reorganization. This mechanism needs to be further understood.

Objective: To explore anatomical and functional visual networks in patients with optic neuritis (ON) to assess the relative weight of each connectivity modality to expedite visual recovery.

Design, setting, and participants: Between March 11, 2011, and May 26, 2014, 39 patients with either clinically isolated syndrome (CIS) ON (n = 18) or other CIS (non-ON) (n = 21) were recruited 1 to 28 months following an initial clinical event. These patients enrolled in an ongoing prospective cohort study (107 participants at the time of this present study) about the disease course of CIS and multiple sclerosis. Inclusion criteria were an age of 18 to 65 years, the suggestive clinical and paraclinical diagnosis of CIS or multiple sclerosis after relevant differential diagnoses have been ruled out, the existence of complete imaging data, and no ocular comorbidities. Anatomical connectivity was evaluated by diffusion tensor imaging, and functional connectivity was evaluated by resting-state functional magnetic resonance imaging. The visual pathways, including optic tracts, optic radiations, and splenial fibers, were delineated, and the resting-state visual networks were detected. Data analysis took place from September 1, 2015, to December 1, 2015.

Main outcomes and measures: Connectivity changes were quantified and compared to determine the association of ON with the visual network.

Results: This study included 18 patients with CIS ON, 11 (61%) of whom were women with a mean (SD) age of 32.83 (8.53) years, and 21 patients with CIS non-ON (11 [52%] of whom were women with a mean [SD] age of 30.86 [7.54] years). With the use of diffusion tensor imaging, reduced diffusivity (mean [SD] fractional anisotropy, 0.35 [0.03] vs 0.38 [0.03]; P < .01) was evident along the optic tracts of patients with ON, suggesting the extension of axonal injury from the damaged optic nerve. Neither the optic radiations nor the splenial fibers showed evidence of loss of integrity. Yet, in the presence of an intact postgeniculate anatomical network, the functional connectivity within the visual network was higher in the ON cohort. Functional connectivity observed in cortical motion-related areas was inversely correlated with the visual evoked potential-measured conduction velocity (r = -0.59; P < .05).

Conclusions and relevance: In this cohort, local optic nerve demyelinating damage does not affect distant wiring, but even in the presence of an intact anatomical network, functional modification may occur. These functional network changes may be part of the recovery process, but further research is needed to elucidate this process.

Conflict of interest statement

Conflict of Interest Disclosures: None reported.

Figures

Figure 1.. Optic Tract (OT) Integrity Impairment Following Damage to the Optic Nerve

A, Visualization of the OTs of a representative patient, as delineated participant by participant via fiber tractography represented in green. B, Fractional anisotropy. C, Axial diffusivity. D, Radial diffusivity profiles along the right OT. LGN indicates lateral geniculate nucleus; ON, optic neuritis. Error bars indicate SD. aFiber section showing significance.

Figure 2.. Absence of Transsynaptic Degeneration in the Optic Radiation (OR)

A, Visualization of the ORs of a representative patient, as delineated participant by participant via fiber tractography represented in light blue. B, Fractional anisotropy profile averaged across 50 positions along the OR in each patient with optic neuritis (ON) and with non-ON. C, Lesion load in the ORs of the 2 cohorts. Error bars indicate SD.

Figure 3.. Absence of Changes in the Callosal Fibers Following Damage to the Afferent Visual Pathway

A, Visualization of the 5 fiber groups and the relative volume they take in the corpus callosum (inset): occipital (red), posterior-parietal (yellow), superior-parietal (green), superior-frontal (blue), and temporal (magenta). B, Association between the volume of occipital callosal fibers (evaluated over the 3 middle sagittal slices) and the volume of the corpus callosum (evaluated over same) compared between patients with optic neuritis (ON) and those with non-ON. It shows that occipital fiber groups in similarly sized corpora callosa take the same relative volume in both groups (similar plots for other fiber groups not shown). C, Fractional anisotropy, axial diffusivity, and radial diffusivity measurements of the occipital callosal fibers compared between patients with ON and those with non-ON. Error bars indicate SD.

Figure 4.. Stronger Functional Connectivity of the Visual Resting-State Network (V-RSN) in Patients With Optic Neuritis (ON) vs Patients With Non-ON

A, Group V-RSN t maps for patients with ON (top panels) and those with non-ON (bottom panels). B, Significant differences between the cohorts were detected using the group t test in the middle temporal (MT, left), lateral occipital complex (LOC, middle), and calcarine sulcus (Calc, right) visual regions (P < .05).

Figure 5.. Correlation of Stronger Functional Connectivity of the Middle Temporal (MT) to the Visual Resting-State Network (V-RSN) With the Projection Rates Along the Visual Pathways

A, Functional connectivity of the right MT region to the V-RSN in patients with optic neuritis (ON) as a function of the ON intereye latency difference (ie, the change in visual evoked potential (ΔVEP, defined as affected eye P100 − fellow eye P100). B, Functional connectivity of the left MT region to the V-RSN in patients with non-ON as a function of mean VEP P100 of the 2 eyes.