Both upper and lower limb disability is common in multiple sclerosis (MS), but do not always occur together, suggesting partially independent underlying mechanisms. Physical disability strongly relates to brain network disturbances in MS, yet network mechanisms underlying upper and lower disability progression remain unclear.
To investigate the relationship between upper and lower limb progression and functional sensorimotor network changes in MS.
Longitudinal data was included from a prospectively acquired cohort, with baseline data collected between 2008 and 2012 and follow-up assessments between 2014 and 2017. Participants underwent MRI and dexterity (9-Hole Peg Test) and mobility (Timed 25-Foot Walk) tests at baseline and after 5 years. Patients were stratified into progressors (>20% decline) or non-progressors for both tests. Measures of network efficiency were calculated from resting-state functional MRI data using both static (i.e. calculated on the entire scan) and dynamic (i.e. fluctuations during the scan) approaches and compared between patient groups. Multiple logistic regression was used to identify independent predictors of upper and lower limb progression and baseline connectivity patterns.
This study included 214 people with MS (age 47±11; 149 women) and 58 healthy controls (age 46±10; 31 women). Compared to respective non-progressors, upper limb progression (n=24) was related to higher dynamic efficiency of the right premotor cortex, somatosensory cortex and thalamus, while lower limb progression (n=37) was related to higher dynamic efficiency of the right supplementary motor area at baseline (p<0.05). Logistic regression showed that dynamic efficiency of the thalamus and supplementary motor area best predicted upper and lower limb progression respectively, independent of the severity of structural damage (p<0.01). Both areas displayed widespread higher dynamic connectivity in progressing compared to non-progressing patients at baseline (p<0.05).
Disability progression can be predicted by the severity of fluctuations (i.e. higher dynamics) in the efficiency of the sensorimotor network. The dynamic behavior of the thalamus and supplementary motor area were respectively related to upper and lower limb progression, possibly indicating different mechanisms underlying these types of progression in MS.