White matter tract network disruption explains reduced conscientiousness in multiple sclerosis

Fuchs, Tom; Dwyer, Michael G.; Kuceyeski, Amy; Choudhery, Sanjeevani; Carolus, Keith; Li, Xian; Mallory, Matthew; Weinstock‐Guttman, Bianca; Jakimovski, Dejan; Ramasamy, Deepa P.; Zivadinov, Robert; Benedict, Ralph H. B.

doi:10.1002/hbm.24203

Cited by 25 publications

(15 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Prior work shows that trait Conscientiousness is associated with less neocortical atrophy 13 and fewer white matter lesions in eloquent fronto-parietal networks. 29 As such, high Conscientiousness indicates spared network disruption which might otherwise cause cognitive decline. Finally, we have also proposed that Conscientiousness is subsumed within the wider neurological reserve construct, as there are synergistic effects between Conscientiousness and traditional measures of cognitive reserve.…”

Section: Discussionmentioning

confidence: 99%

Trait Conscientiousness predicts rate of longitudinal SDMT decline in multiple sclerosis

et al. 2019

Self Cite

View full text Add to dashboard Cite

Background: Many people with multiple sclerosis (MS) exhibit cognitive decline over several years. Baseline differences may put people at greater risk for such decline. Objective: To characterize rates of longitudinal cognitive decline and investigate baseline clinical predictors. Methods: We report a retrospective analysis of 531 MS patients whose data were gleaned from a multi-study database, aggregated over 16 years. Linear mixed effects modeling was applied to estimate the average rate of decline on Symbol Digit Modalities Test (SDMT) performance and to predict rates of decline using baseline clinical variables. Results: Participants exhibited an average estimated decline of 0.22 SDMT raw-score points/year (95% confidence interval (CI) (−0.32, −0.12)). We observed a significant main effect of time from baseline ( t = −2.78, p = 0.006), test form ( t = 2.13, p = 0.034), disease course ( t = 2.91, p = 0.004), age ( t = −2.76, p = 0.006), sex ( t = −2.71, p = 0.007), subjective cognitive impairment ( t = −2.00, p = 0.046), premorbid verbal intelligence ( t = 5.14, p < 0.001), and trait Conscientiousness ( t = 2.69, p = 0.008). A significant interaction emerged for Conscientiousness and time from baseline ( t = 2.57, p = 0.011). Conclusion: Higher baseline trait Conscientiousness predicts slower rates of longitudinal cognitive decline in MS. This relationship, the average rate of decline, and practice effects can inform future research and clinical treatment decisions.

show abstract

Section: Discussionmentioning

confidence: 99%

Trait Conscientiousness predicts rate of longitudinal SDMT decline in multiple sclerosis

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…Additional details can be found in a previous publication (Fuchs et al, 2018). Additional details can be found in a previous publication (Fuchs et al, 2018).…”

Section: Preservation Of Functional Connectivity and The Structure-mentioning

confidence: 99%

“…To measure changes in structural connectivity caused by damage to WM tracts, the transformed WM lesion masks were processed with the Network Modification (NeMo) tool (Kuceyeski, Maruta, Relkin, & Raj, 2013). Our use of this approach has been previously described (Fuchs et al, 2018). In short, this tool infers changes to the structural connectivity network resulting from the WM lesion mask by referencing a within-software database of 73 healthy control tractograms.…”

Section: T2-flair Wm Lesion Masks and Measures Of T2 Lesion Volumementioning

confidence: 99%

“…As stated above, the step of identifying pertinent structural networks for each cognitive domain was accomplished using NBS, a method for controlling family-wise error while retaining power by accounting for network structure-and is similar to more conventional cluster statistics. Additional details can be found in a previous publication (Fuchs et al, 2018). To maximize statistical power for this step of network identification, a larger cohort of PwMS was used (n = 137), including individuals without fMRI.…”

Section: Preservation Of Functional Connectivity and The Structure-mentioning

confidence: 99%

See 1 more Smart Citation

Preserved network functional connectivity underlies cognitive reserve in multiple sclerosis

Fuchs

Benedict

Bartnik

et al. 2019

Human Brain Mapping

Self Cite

View full text Add to dashboard Cite

Cognitive reserve is one's mental resilience or resistance to the effects of structural brain damage. Reserve effects are well established in people with multiple sclerosis (PwMS) and Alzheimer's disease, but the neural basis of this phenomenon is unclear. We aimed to investigate whether preservation of functional connectivity explains cognitive reserve. Seventy‐four PwMS and 29 HCs underwent neuropsychological assessment and 3 T MRI. Structural damage measures included gray matter (GM) atrophy and network white matter (WM) tract disruption between pairs of GM regions. Resting‐state functional connectivity was also assessed. PwMS exhibited significantly impaired cognitive processing speed (t = 2.14, p = .037) and visual/spatial memory (t = 2.72, p = .008), and had significantly greater variance in functional connectivity relative to HCs within relevant networks (p < .001, p < .001, p = .016). Higher premorbid verbal intelligence, a proxy for cognitive reserve, predicted relative preservation of functional connectivity despite accumulation of GM atrophy (standardized‐β = .301, p = .021). Furthermore, preservation of functional connectivity attenuated the impact of structural network WM tract disruption on cognition (β = −.513, p = .001, for cognitive processing speed; β = −.209, p = .066, for visual/spatial memory). The data suggests that preserved functional connectivity explains cognitive reserve in PwMS, helping to maintain cognitive capacity despite structural damage.

show abstract

“…This approach has been used by our group and others to relate lesion-related structural disconnectivity patterns to impairments, outcomes, functional connectivity disruptions, rehabilitation response and gray matter pathology in pwMS (T. A. Tom A. Fuchs et al, 2018, 2020A. F. Kuceyeski et al, 2015;.…”

Section: Introductionmentioning

confidence: 99%

Structural disconnectivity from quantitative susceptibility mapping rim+ lesions is related to disability in people with multiple sclerosis

Tozlu

Jamison

Nguyen

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

BackgroundMultiple Sclerosis (MS) is a disease characterized by inflammation, demyelination, and/or axonal loss that disrupts white matter pathways that constitute the brain’s structural connectivity network. Individual disease burden and disability in patients with MS (pwMS) varies widely across the population, possibly due to heterogeneity of lesion location, size and subsequent disruption of the structural connectome. Chronic active MS lesions, which have a hyperintense rim (rim+) on Quantitative Susceptibility Mapping (QSM) and a rim of iron-laden inflammatory cells, have been shown to be particularly detrimental to tissue concentration causing greater myelin damage compared to chronic silent MS lesions. How these rim+ lesions differentially impact structural connectivity and subsequently influence disability has not yet been explored.ObjectiveWe characterize differences in the spatial location and structural disconnectivity patterns of rim+ lesions compared to rimlesions. We test the hypothesis that rim+ lesions’ disruption to the structural connectome are more predictive of disability compared to rimlesions’ disruption to the structural connectome. Finally, we quantify the most important regional structural connectome disruptions for disability prediction in pwMS.MethodsNinety-six pwMS were included in our study (age: 40.25 ± 10.14, 67% female). Disability was assessed using Extended Disability Status Score (EDSS); thirty-seven pwMS had disability (EDSS ≥ 2). Regional structural disconnectivity patterns due to rim- and rim+ lesions were estimated using the Network Modification (NeMo) Tool. For each gray matter region, the NeMo Tool calculates a Change in Connectivity (ChaCo) score, i.e. the percent of connecting streamlines also passing through a lesion. Adaptive Boosting (ADA) classifiers were constructed based on demographics and the two sets of ChaCo scores (from rim+ and rim- lesions); performance was compared across the two models using the area under ROC curve (AUC). Finally, the importance of structural disconnectivity in each brain region in the disability prediction models was determined.ResultsRim+ lesions were much larger and tended to be more periventricular than rim- lesions. The model based on rim+ lesion structural disconnectivity measures had better disability classification performance (AUC = 0.67) than the model based on rim- lesion structural disconnectivity (AUC = 0.63). Structural disconnectivity, from both rim+ and rim- lesions, in the left thalamus and left cerebellum were most important for classifying pwMS into disability categories.ConclusionOur findings suggest that, independent of the evidence that they have more damaging pathology, rim+ lesions also may be more influential on disability through their disruptions to the structural connectome. Furthermore, lesions of any type in the left cerebellum and left thalamus were especially important in classifying disability in pwMS. This analysis provides a deeper understanding of how lesion location/size and resulting disruption to the structural connectome can contribute to MS-related disability.

show abstract

White matter tract network disruption explains reduced conscientiousness in multiple sclerosis

Cited by 25 publications

References 41 publications

Trait Conscientiousness predicts rate of longitudinal SDMT decline in multiple sclerosis

Trait Conscientiousness predicts rate of longitudinal SDMT decline in multiple sclerosis

Preserved network functional connectivity underlies cognitive reserve in multiple sclerosis

Structural disconnectivity from quantitative susceptibility mapping rim+ lesions is related to disability in people with multiple sclerosis

Contact Info

Product

Resources

About