Contributions
Abstract: P516
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Imaging
Background: Atrophy of the deep grey matter (DGM) is a common and early finding in MS, while cortical atrophy seems to be more frequent in later phases. It is currently unknown, however, how functional connectivity of the cortex and DGM changes in the different stages of MS and how this relates to cognition.
Aim: To investigate changes in functional connections within and between cortical and DGM areas in early relapsing remitting (RR), late RR and secondary progressive (SP) MS.
Method: A cohort of 243 RRMS patients, 53 SPMS patients and 96 healthy controls underwent resting state functional MRI and extensive neuropsychological testing. Using a median split on disease duration, 121 RRMS patients were classified as early (mean disease duration 7 (5-10) years) and 122 as late RRMS (mean disease duration 20 (10-38) years). The groups were compared by looking at (1) the averaged within-DGM connectivity, (2) the averaged within-cortex connectivity and (3) the averaged DGM-cortex connectivity. Connectivity values were corrected for individual means and standard deviations in order to specifically look at network balance changes (i.e. relative connectivity) and compared between groups using general linear models with sex and education as covariates (p< 0.05, Bonferroni corrected). In order to assess the additive value of connectivity beyond structural measures, forced-entry linear regression models were used for each network measure to predict the most severely affected cognitive domain in SPMS.
Results: SPMS patients showed decreased within-cortex connectivity and increased within-DGM connectivity compared to early RRMS. Late RRMS showed increased within-DGM connectivity compared to early RRMS, with no change in within-cortex connectivity. The connections between cortical and DGM regions were stronger in SPMS and late RRMS compared to early RRMS and HC. In SPMS, increased within-DGM connectivity (β=-0.270) and decreased normalised DGM volume (β=0.540) were the only significant predictors for information processing speed (IPS) dysfunction (R2=0.37).
Conclusion: In late RRMS and SPMS, increased connectivity within the DGM and between the DGM and the cortex was observed compared to early RRMS. These connectivity changes were associated with IPS. Decreased within-cortex connectivity was unique to SPMS. These findings indicate that a specific shift in network balance occurs throughout the disease course, which needs to be confirmed in future longitudinal studies.
Disclosure:
KA Meijer: nothing to disclose and receives funding from a Biogen research grant
AJC Eijlers: nothing to disclose and receives research support from the Dutch MS Research Foundation, grant 14-358e
JJG Geurts: nothing to disclose
MM Schoonheim: nothing to disclose and receives research support from the Dutch MS Research Foundation, grant 13-820
Abstract: P516
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Imaging
Background: Atrophy of the deep grey matter (DGM) is a common and early finding in MS, while cortical atrophy seems to be more frequent in later phases. It is currently unknown, however, how functional connectivity of the cortex and DGM changes in the different stages of MS and how this relates to cognition.
Aim: To investigate changes in functional connections within and between cortical and DGM areas in early relapsing remitting (RR), late RR and secondary progressive (SP) MS.
Method: A cohort of 243 RRMS patients, 53 SPMS patients and 96 healthy controls underwent resting state functional MRI and extensive neuropsychological testing. Using a median split on disease duration, 121 RRMS patients were classified as early (mean disease duration 7 (5-10) years) and 122 as late RRMS (mean disease duration 20 (10-38) years). The groups were compared by looking at (1) the averaged within-DGM connectivity, (2) the averaged within-cortex connectivity and (3) the averaged DGM-cortex connectivity. Connectivity values were corrected for individual means and standard deviations in order to specifically look at network balance changes (i.e. relative connectivity) and compared between groups using general linear models with sex and education as covariates (p< 0.05, Bonferroni corrected). In order to assess the additive value of connectivity beyond structural measures, forced-entry linear regression models were used for each network measure to predict the most severely affected cognitive domain in SPMS.
Results: SPMS patients showed decreased within-cortex connectivity and increased within-DGM connectivity compared to early RRMS. Late RRMS showed increased within-DGM connectivity compared to early RRMS, with no change in within-cortex connectivity. The connections between cortical and DGM regions were stronger in SPMS and late RRMS compared to early RRMS and HC. In SPMS, increased within-DGM connectivity (β=-0.270) and decreased normalised DGM volume (β=0.540) were the only significant predictors for information processing speed (IPS) dysfunction (R2=0.37).
Conclusion: In late RRMS and SPMS, increased connectivity within the DGM and between the DGM and the cortex was observed compared to early RRMS. These connectivity changes were associated with IPS. Decreased within-cortex connectivity was unique to SPMS. These findings indicate that a specific shift in network balance occurs throughout the disease course, which needs to be confirmed in future longitudinal studies.
Disclosure:
KA Meijer: nothing to disclose and receives funding from a Biogen research grant
AJC Eijlers: nothing to disclose and receives research support from the Dutch MS Research Foundation, grant 14-358e
JJG Geurts: nothing to disclose
MM Schoonheim: nothing to disclose and receives research support from the Dutch MS Research Foundation, grant 13-820