Summary metrics of memory subnetwork functional connectivity alterations in multiple sclerosis

Abstract

Memory dysfunction is common in multiple sclerosis (MS); mechanistic understanding of its causes is lacking. Large-scale network resting-state functional connectivity (RSFC) is sensitive to memory dysfunction. Here, we sought to derive and test summary metrics of memory network RSFC. Cognitive data and 3T magnetic resonance imaging (MRI) scans were collected from 235 MS patients and 35 healthy controls (HCs). Index scores were calculated as RSFC within (anteriority index, AntI) and between (integration index, IntI) dorsomedial anterior temporal and medial temporal memory subnetworks. Group differences in index expression were evaluated. Associations between index scores and memory/non-memory cognition were evaluated; relationships between T2 lesion volume (T2LV) and index scores were assessed. Index scores were related to memory and T2LV in MS patients, who showed marginally elevated AntI relative to HC (p=0.06); no group differences were found for IntI. Better memory was associated with higher AntI (β=0.15, p=0.018) and IntI (β=0.16, p=0.014). No associations were found for non-memory cognition. Higher T2LV was associated with higher AntI and IntI; exploratory mediation analysis revealed significant inconsistent mediation, that is, higher index scores partially suppressed the negative association between T2LV and memory. Summary, within-subject metrics permit replication and circumvent challenges of traditional (incommensurate) RSFC variables to advance development of mechanistic models of memory dysfunction in MS.