Reduced Intrinsic Connectivity Secondary to Multiple Sclerosis as a Functional Marker of Impaired Verbal Memory Encoding and Retrieval
Viviane Tavares Carvalho Crelier1, Jonadab Dos Santos Silva2, Vanessa Dias Veloso3, Sarita Walvekar2, Luciana Schermann Azambuja4, Adriana Gutterres Pereira4, Giordani Passos4, Douglas Sato4, Jefferson Becker4
1Universidade Federal Fluminense, 2Yale School of Medicine, 3Yale New Haven Hospital, 4Pontifícia Universidade Católica do Rio Grande do Sul
Objective:
We aimed to investigate the differences in cerebral intrinsic connectivity between people with multiple sclerosis (pwMS) and healthy controls (HC) and their associations with verbal memory.
Background:
In MS, multifocal lesions and widespread inflammation contribute to brain network changes, and structural disruptions lead to maladaptive functional reorganization with clinical implications. Verbal memory is common and debilitating in MS.
Design/Methods:
Included were 23 pwMS (median age 28.5yr, range 28–62; 42% female; median disease duration 1 year, range 0–11) and 10 HC (median age 28yr, range 20–48; 36% female). Participants underwent verbal memory assessment using the Wechsler Memory Scale-III and 3T MRI (T1-weighted MPRAGE, FLAIR, and resting-state functional MRI [rs-fMRI]). White matter lesions (WML) were semiautomatically segmented. Using rs-fMRI, whole-brain intrinsic connectivity (ICC) maps were estimated. Group-level analyses utilized a voxel-wise general linear model, with familywise correction at a p-FWE<0.05 cluster-size threshold.
Results:
PwMS exhibited diffusely lower intrinsic connectivity (T = -4.35, p-FDR < 0.001). Voxel-wise meta-regression analysis of MS effect in ICC revealed association with areas related to reward (meta-analytic coactivation [r] = 0.25), motivation (r = 0.15), and working memory (r = 0.11). A generalized linear model adjusted for age, sex, WML volume, and disease duration revealed that the effect of MS in ICC was an independent predictor of poorer verbal learning in the immediate recall phase (B = -9.14, 95% CI [-15.61, -2.70], P = 0.006), delayed recall phase (B = -10.77, 95% CI [-19.99, -1.54], P = 0.022), and retention rate (B = -4.89, 95% CI [-8.86, -0.927], P = 0.0016).
Conclusions:
MS is related to lower cerebral intrinsic connectivity, and this disruption secondary to MS is associated with worse verbal memory in both early and delayed phases of encoding and retrieval, unraveling the potential of resting-state intrinsic connectivity to be used as disease-related functional biomarker of working memory in multiple sclerosis.
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