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Long-range connections are more severely damaged and relevant for cognition in multiple sclerosis.
Brain. 2020 01 01; 143(1):150-160.B

Abstract

An efficient network such as the human brain features a combination of global integration of information, driven by long-range connections, and local processing involving short-range connections. Whether these connections are equally damaged in multiple sclerosis is unknown, as is their relevance for cognitive impairment and brain function. Therefore, we cross-sectionally investigated the association between damage to short- and long-range connections with structural network efficiency, the functional connectome and cognition. From the Amsterdam multiple sclerosis cohort, 133 patients (age = 54.2 ± 9.6) with long-standing multiple sclerosis and 48 healthy controls (age = 50.8 ± 7.0) with neuropsychological testing and MRI were included. Structural connectivity was estimated from diffusion tensor images using probabilistic tractography (MRtrix 3.0) between pairs of brain regions. Structural connections were divided into short- (length < quartile 1) and long-range (length > quartile 3) connections, based on the mean distribution of tract lengths in healthy controls. To determine the severity of damage within these connections, (i) fractional anisotropy as a measure for integrity; (ii) total number of fibres; and (iii) percentage of tract affected by lesions were computed for each connecting tract and averaged for short- and long-range connections separately. To investigate the impact of damage in these connections for structural network efficiency, global efficiency was computed. Additionally, resting-state functional connectivity was computed between each pair of brain regions, after artefact removal with FMRIB's ICA-based X-noiseifier. The functional connectivity similarity index was computed by correlating individual functional connectivity matrices with an average healthy control connectivity matrix. Our results showed that the structural network had a reduced efficiency and integrity in multiple sclerosis relative to healthy controls (both P < 0.05). The long-range connections showed the largest reduction in fractional anisotropy (z = -1.03, P < 0.001) and total number of fibres (z = -0.44, P < 0.01), whereas in the short-range connections only fractional anisotropy was affected (z = -0.34, P = 0.03). Long-range connections also demonstrated a higher percentage of tract affected by lesions than short-range connections, independent of tract length (P < 0.001). Damage to long-range connections was more strongly related to structural network efficiency and cognition (fractional anisotropy: r = 0.329 and r = 0.447. number of fibres r = 0.321 and r = 0.278. and percentage of lesions: r = -0.219; r = -0.426, respectively) than damage to short-range connections. Only damage to long-distance connections correlated with a more abnormal functional network (fractional anisotropy: r = 0.226). Our findings indicate that long-range connections are more severely affected by multiple sclerosis-specific damage than short-range connections. Moreover compared to short-range connections, damage to long-range connections better explains network efficiency and cognition.

Authors+Show Affiliations

Department of Anatomy and Neurosciences, Amsterdam Neuroscience, MS Center Amsterdam, Amsterdam UMC location VU University Medical Center, Amsterdam, The Netherlands.Department of Anatomy and Neurosciences, Amsterdam Neuroscience, MS Center Amsterdam, Amsterdam UMC location VU University Medical Center, Amsterdam, The Netherlands.Department of Anatomy and Neurosciences, Amsterdam Neuroscience, MS Center Amsterdam, Amsterdam UMC location VU University Medical Center, Amsterdam, The Netherlands. Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts, USA.Department of Anatomy and Neurosciences, Amsterdam Neuroscience, MS Center Amsterdam, Amsterdam UMC location VU University Medical Center, Amsterdam, The Netherlands.Department of Anatomy and Neurosciences, Amsterdam Neuroscience, MS Center Amsterdam, Amsterdam UMC location VU University Medical Center, Amsterdam, The Netherlands.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31730165

Citation

Meijer, Kim A., et al. "Long-range Connections Are More Severely Damaged and Relevant for Cognition in Multiple Sclerosis." Brain : a Journal of Neurology, vol. 143, no. 1, 2020, pp. 150-160.
Meijer KA, Steenwijk MD, Douw L, et al. Long-range connections are more severely damaged and relevant for cognition in multiple sclerosis. Brain. 2020;143(1):150-160.
Meijer, K. A., Steenwijk, M. D., Douw, L., Schoonheim, M. M., & Geurts, J. J. G. (2020). Long-range connections are more severely damaged and relevant for cognition in multiple sclerosis. Brain : a Journal of Neurology, 143(1), 150-160. https://doi.org/10.1093/brain/awz355
Meijer KA, et al. Long-range Connections Are More Severely Damaged and Relevant for Cognition in Multiple Sclerosis. Brain. 2020 01 1;143(1):150-160. PubMed PMID: 31730165.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Long-range connections are more severely damaged and relevant for cognition in multiple sclerosis. AU - Meijer,Kim A, AU - Steenwijk,Martijn D, AU - Douw,Linda, AU - Schoonheim,Menno M, AU - Geurts,Jeroen J G, PY - 2019/04/02/received PY - 2019/08/06/revised PY - 2019/09/21/accepted PY - 2019/11/16/pubmed PY - 2020/8/19/medline PY - 2019/11/16/entrez KW - MRI KW - cognition KW - functional brain network KW - multiple sclerosis KW - structural brain network SP - 150 EP - 160 JF - Brain : a journal of neurology JO - Brain VL - 143 IS - 1 N2 - An efficient network such as the human brain features a combination of global integration of information, driven by long-range connections, and local processing involving short-range connections. Whether these connections are equally damaged in multiple sclerosis is unknown, as is their relevance for cognitive impairment and brain function. Therefore, we cross-sectionally investigated the association between damage to short- and long-range connections with structural network efficiency, the functional connectome and cognition. From the Amsterdam multiple sclerosis cohort, 133 patients (age = 54.2 ± 9.6) with long-standing multiple sclerosis and 48 healthy controls (age = 50.8 ± 7.0) with neuropsychological testing and MRI were included. Structural connectivity was estimated from diffusion tensor images using probabilistic tractography (MRtrix 3.0) between pairs of brain regions. Structural connections were divided into short- (length < quartile 1) and long-range (length > quartile 3) connections, based on the mean distribution of tract lengths in healthy controls. To determine the severity of damage within these connections, (i) fractional anisotropy as a measure for integrity; (ii) total number of fibres; and (iii) percentage of tract affected by lesions were computed for each connecting tract and averaged for short- and long-range connections separately. To investigate the impact of damage in these connections for structural network efficiency, global efficiency was computed. Additionally, resting-state functional connectivity was computed between each pair of brain regions, after artefact removal with FMRIB's ICA-based X-noiseifier. The functional connectivity similarity index was computed by correlating individual functional connectivity matrices with an average healthy control connectivity matrix. Our results showed that the structural network had a reduced efficiency and integrity in multiple sclerosis relative to healthy controls (both P < 0.05). The long-range connections showed the largest reduction in fractional anisotropy (z = -1.03, P < 0.001) and total number of fibres (z = -0.44, P < 0.01), whereas in the short-range connections only fractional anisotropy was affected (z = -0.34, P = 0.03). Long-range connections also demonstrated a higher percentage of tract affected by lesions than short-range connections, independent of tract length (P < 0.001). Damage to long-range connections was more strongly related to structural network efficiency and cognition (fractional anisotropy: r = 0.329 and r = 0.447. number of fibres r = 0.321 and r = 0.278. and percentage of lesions: r = -0.219; r = -0.426, respectively) than damage to short-range connections. Only damage to long-distance connections correlated with a more abnormal functional network (fractional anisotropy: r = 0.226). Our findings indicate that long-range connections are more severely affected by multiple sclerosis-specific damage than short-range connections. Moreover compared to short-range connections, damage to long-range connections better explains network efficiency and cognition. SN - 1460-2156 UR - https://www.unboundmedicine.com/medline/citation/31730165/Long_range_connections_are_more_severely_damaged_and_relevant_for_cognition_in_multiple_sclerosis_ DB - PRIME DP - Unbound Medicine ER -