Altered Brain Structure and Functional Connectivity of Primary Visual Cortex in Optic Neuritis

Previous studies have revealed brain adaptations to injury that occurs in optic neuritis (ON); however, the mechanisms underlying the functional connectivity (FC) and gray matter volume (GMV) changes in ON have not been clarified. Here, 51 single attack ON patients and 45 recurrent attacks ON patients were examined using structural MRI and resting-state functional MRI (RS-fMRI), and compared to 49 age- and gender-matched healthy controls (HC). FC analysis with a seed in primary visual cortex (V1 area) was used to assess the differences among three groups. Whole brain GMV was assessed using voxel-based morphometry (VBM). Correlation analyses were performed between FC results, structural MRI and clinical variables. We found positive correlations between the Paced Auditory Serial Addition Test (PASAT) score and FC in V1 area with bilateral middle frontal gyrus. Disease duration is significantly negatively related to FC in V1 area with the left inferior parietal lobule. Compared to the HC, single attack ON patients were found to have decreased FC values in the frontal, temporal lobes, right inferior occipital gyrus, right insula, right inferior parietal lobule, and significant increased FC values in the left thalamus. Recurrent attacks ON patients had the same pattern with single attack ON. No significant differences were found in brain GMV among three groups. This study provides the imaging evidence that impairment and compensation of V1 area connectivity coexist in ON patients, and provides important insights into the underlying neural mechanisms of ON

Baseline Brain Activity Changes in Patients With Single and Relapsing Optic Neuritis

Purpose: To investigate spontaneous brain activity amplitude alterations in single and relapsing optic neuritis (sON and rON, respectively) and their relationships with clinical variables.Methods: In total, 42 patients with sON, 35 patients with rON and 50 healthy volunteers were recruited. Resting-state functional Magnetic Resonance Imaging (rs-fMRI) scans were acquired for all participants and compared to investigate the changes in the amplitude of low-frequency fluctuations (ALFFs) among the three groups. The relationships between the ALFFs in regions with significant differences in the groups and clinical variables, including the logarithm of minimal angle of resolution (LogMAR), Expanded Disability Status Scale (EDSS) score and disease duration, were further explored.Results: Compared with healthy volunteers, the sON and rON patients showed significantly decreased ALFFs in several regions of the occipital and temporal lobes (i.e., inferior occipital gyrus and superior temporal gyrus; corrected p < 0.01 using AlphaSim). The sON patients showed significantly increased ALFFs in the left caudate and certain regions in the frontal lobes (i.e., medial frontal gyrus), whereas the rON patients showed increased ALFFs in the bilateral inferior temporal gyrus and left medial frontal gyrus (corrected p < 0.01 using AlphaSim). Significantly decreased ALFFs were observed in the right inferior parietal lobule (IPL), left posterior cingulate and precuneus in the rON patients compared with those in the sON patients (corrected p < 0.01 using AlphaSim). Significant correlations were observed between the disease duration and ALFF in the left middle temporal gyrus, left inferior occipital gyrus, right lingual gyrus and right IPL (p < 0.05).Conclusion: Functional impairment and adaptation occurred in both the sON and rON patients. Impairment mainly involved the occipital cortex, and functional adaptions predominantly occurred in the frontal lobe. Functional damage was more severe in the rON patients than in the sON patients and correlated with the disease duration

Progressive brain rich-club network disruption from clinically isolated syndrome towards multiple sclerosis

Objective: To investigate the rich-club organization in clinically isolated syndrome (CIS) and multiple sclerosis (MS), and to characterize its relationships with physical disabilities and cognitive impairments. Methods: We constructed high-resolution white matter (WM) structural networks in 41 CIS, 32 MS and 35 healthy controls (HCs) using diffusion MRI and deterministic tractography. Group differences in rich-club organization, global and local network metrics were investigated. The relationship between the altered network metrics, brain lesions and clinical variables including EDSS, MMSE, PASAT, disease duration were calculated. Additionally, reproducibility analysis was performed using different parcellation schemes. Results: Compared with HCs, MS patients exhibited a decreased strength in all types of connections (rich-club: p < 0.0001; feeder: p = 0.0004; and local: p = 0.0026). CIS patients showed intermediate values between MS patients and HCs and exhibited a decreased strength in feeder and local connections (feeder: p = 0.019; and local: p = 0.031) but not in rich-club connections. Compared with CIS patients, MS patients showed significant reductions in rich-club connections (p = 0.0004). The reduced strength of rich-club and feeder connections was correlated with cognitive impairments in the MS group. These results were independent of lesion distribution and reproducible across different brain parcellation schemes. Conclusion: The rich-club organization was disrupted in MS patients and relatively preserved in CIS. The disrupted rich-club connectivity was correlated with cognitive impairment in MS. These findings suggest that impaired rich-club connectivity is an essential feature of progressive structural network disruption, heralding the development of clinical disability in MS

Multimodal characterization of gray matter alterations in neuromyelitis optica

OBJECTIVE: To investigate structural and functional alterations of gray matter (GM) and examine their clinical relevance in neuromyelitis optica (NMO) using multimodal magnetic resonance imaging (MRI) techniques. METHODS: A total of 35 NMO and 36 healthy controls (HC) were recruited in this study. Cortical lesions were investigated by double inversion recovery technique. Five voxel-wise MRI measurements were obtained for each participant in the GM including gray matter volume (GMV), fractional anisotropy (FA), mean diffusivity (MD), amplitude of low-frequency fluctuation (ALFF), and weighted functional connectivity strength (wFCS). Between-group differences, cross-modality relationships, and MRI-clinical correlations were examined. RESULTS: No cortical lesions were found in NMO. Compared to HC, NMO patients exhibited significantly decreased GMV in deep GM and cortical regions involving visual function and cognition. Diffusion GM abnormalities were widespread in the patients. Decreased ALFF and wFCS were observed in the patients in sensorimotor, visual, cognition, and cerebellar sites. GM structural alterations were correlated with cognitive but not physical disability scores of the patients. CONCLUSION: Despite the lack of focal cortical lesions, patients with NMO exhibit both structural and functional alterations of GM in cerebrum and cerebellum that predominantly involve deep GM, visual, motor, and cognitive regions. GM alterations are associated with cognitive impairment but not physical disability

Whole brain functional connectivity in clinically isolated syndrome without conventional brain MRI lesions

Objective To investigate brain functional connectivity (FC) alterations in patients with clinically isolated syndromes (CIS) presenting without conventional brain MRI lesions, and to identify the FC differences between the CIS patients who converted to multiple sclerosis (MS) and those not converted during a 5-year follow-up. Methods We recruited 20 CIS patients without conventional brain lesions, 28 patients with MS and 28 healthy controls (HC). Normalized voxel-based functional connectivity strength (nFCS) was determined using resting-state fMRI (R-fMRI) and compared among groups. Furthermore, 5-years clinical follow-up of the CIS patients was performed to examine the differences in nFCS between converters and non-converters. Results Compared to HC, CIS patients showed significantly decreased nFCS in the visual areas and increased nFCS in several brain regions predominately in the temporal lobes. MS patients revealed more widespread higher nFCS especially in deep grey matter (DGM), compared to CIS and HC. In the four CIS patients converting to MS, significantly higher nFCS was found in right anterior cingulate gyrus (ACC) and fusiform gyrus (FG), compared to non-converted patients. Conclusion We demonstrated both functional impairment and compensation in CIS by R-fMRI. nFCS alteration in ACC and FG seems to occur in CIS patients at risk of developing MS

Disrupted topological organization of structural and functional brain connectomes in clinically isolated syndrome and multiple sclerosis

The brain connectome of multiple sclerosis (MS) has been investigated by several previous studies; however, it is still unknown how the network changes in clinically isolated syndrome (CIS), the earliest stage of MS, and how network alterations on a functional level relate to the structural level in MS disease. Here, we investigated the topological alterations of both the structural and functional connectomes in 41 CIS and 32 MS patients, compared to 35 healthy controls, by combining diffusion tensor imaging and resting-state functional MRI with graph analysis approaches. We found that the structural connectome showed a deviation from the optimal pattern as early as the CIS stage, while the functional connectome only showed local changes in MS patients, not in CIS. When comparing two patient groups, the changes appear more severe in MS. Importantly, the disruptions of structural and functional connectomes in patients occurred in the same direction and locally correlated in sensorimotor component. Finally, the extent of structural network changes was correlated with several clinical variables in MS patients. Together, the results suggested early disruption of the structural brain connectome in CIS patients and provided a new perspective for investigating the relationship of the structural and functional alterations in MS