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Functional network dynamics and decreased conscientiousness in multiple sclerosis

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Abstract

Background

Conscientiousness is a personality trait that declines in people with multiple sclerosis (PwMS) and its decline predicts worse clinical outcomes. This study aims to investigate the neural underpinnings of lower Conscientiousness in PwMS by examining MRI anomalies in functional network dynamics.

Methods

70 PwMS and 50 healthy controls underwent personality assessment and resting-state MRI. Associations with dynamic functional network properties (i.e., eigenvector centrality) were evaluated, using a dynamic sliding-window approach.

Results

In PwMS, lower Conscientiousness was associated with increased variability of centrality in the left insula (tmax = 4.21) and right inferior parietal lobule (tmax = 3.79); a relationship also observed in regressions accounting for handedness, disease duration, disability, and tract disruption in relevant structural networks (ΔR2 = 0.071, p = 0.003; ΔR2 = 0.094, p = 0.004). Centrality dynamics of the observed regions were not associated with Neuroticism (R2 < 0.001, p = 0.956; R2 < 0.001, p = 0.945). As well, higher Conscientiousness was associated with greater variability in connectivity for the left insula with the default-mode network (F = 3.92, p = 0.023) and limbic network (F = 5.66, p = 0.005).

Conclusion

Lower Conscientiousness in PwMS was associated with increased variability in network centrality, most prominently for the left insula and right inferior parietal cortex. This effect, specific to Conscientiousness and significant after accounting for disability and structural network damage, could indicate that overall stable network centrality is lost in patients with low Conscientiousness, especially for the insula and right parietal cortex. The positive relationship between Conscientiousness and variability of connectivity between left insula and default-mode network potentially affirms that dynamics between the salience and default-mode networks is related to the regulation of behavior.

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Funding

The data that support the findings of this study are available from the corresponding author, upon reasonable request. This study was completed without institutional, private, or corporate financial support.

Author information

Authors and Affiliations

  1. Buffalo Neuroimaging Analysis Center, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA

    Tom A. Fuchs, Dejan Jakimovski, Robert Zivadinov & Michael G. Dwyer

  2. Jacobs Multiple Sclerosis Center for Treatment and Research, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA

    Tom A. Fuchs, Bianca Weinstock-Guttman, Robert Zivadinov, Michael G. Dwyer & Ralph H. B. Benedict

  3. Department of Anatomy and Neurosciences, MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands

    Menno M. Schoonheim, Tommy A. A. Broeders, Hanneke E. Hulst & Jeroen J. G. Geurts

  4. Department of Orthopedics, School of Medicine, University of Connecticut, Farmington, CT, USA

    Jacob Silver

  5. Center for Biomedical Imaging, Clinical Translational Science Institute, University at Buffalo, State University of New York, Buffalo, NY, USA

    Robert Zivadinov & Michael G. Dwyer

Authors
  1. Tom A. Fuchs
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  2. Menno M. Schoonheim
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  11. Ralph H. B. Benedict
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Corresponding author

Correspondence to Ralph H. B. Benedict.

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Conflicts of interest

Tom Fuchs, Tommy Broeders, Jacob Silver, and Dejan Jakimovski have nothing to declare. Menno Schoonheim serves on the editorial board of Frontiers of Neurology and has received research support, compensation for consulting services or speaker honoraria from the Dutch MS Research Foundation, ARSEP, Eurostars-EUREKA, ZonMW, ExceMed, Amsterdam Neuroscience, Atara, Biogen, Celgene/BMS, Merck, MedDay and Sanofi-Genzyme. Hanneke E. Hulst serves in the editorial board of MSJ and has received compensation for consulting services or speaker honoraria from Sanofi Genzyme, Biogen Idec, Celgene, and Merck. BV. Bianca Weinstock-Guttman received honoraria as a speaker and as a consultant for Biogen Idec, Teva Pharmaceuticals, EMD Serono, Genzyme, Sanofi, Novartis and Acorda. Dr Weinstock-Guttman received research funds from Biogen Idec, Teva Pharmaceuticals, EMD Serono, Genzyme, Sanofi, Novartis, and Acorda. Robert Zivadinov received personal compensation from EMD Serono, Sanofi, Novartis, Bristol Myers Squibb, and Keystone Heart for speaking and consultant fees. He received financial support for research activities from Sanofi, Novartis, Bristol Myers Squibb, Mapi Pharma, Keystone Heart, V-VAWE Medical, Boston Scientific and Protembo. Jeroen Geurts is an editor of Multiple Sclerosis Journal and is president of the Netherlands organization for health research and innovation. He has received research support or compensation for consulting services from the Dutch MS Research Foundation, Ammodo, Eurostars-EUREKA, Biogen, Celgene/BMS, Merck, MedDay, Novartis and Sanofi-Genzyme. Michael G. Dwyer has received consultant fees from Claret Medical and EMD Serono and research Grant support from Novartis. Ralph HB Benedict receives research support from Biogen, Bristol Meyers Squibb, Genzyme, Genentech, Novartis, National Institutes of Health, National Multiple Sclerosis Society, and Verasci. Dr. Benedict has received compensation for speaking and consulting services from Immunic Therapeutics, Latin American Committee for Treatment and Research in Multiple Sclerosis, Merck, Novartis, Roche, Sanofi, Biogen, Bristol Meyers Squibb, and EMD Serono, and receives royalties from Psychological Assessment Resources.

Ethical approval

The study protocol was approved by the University at Buffalo Institutional Ethics Review Board.

Informed consent

All subjects provided written informed consent before participation.

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Fuchs, T.A., Schoonheim, M.M., Broeders, T.A.A. et al. Functional network dynamics and decreased conscientiousness in multiple sclerosis. J Neurol 269, 2696–2706 (2022). https://doi.org/10.1007/s00415-021-10860-8

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  • DOI: https://doi.org/10.1007/s00415-021-10860-8

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