Altered resting-state functional connectivity in cognitively preserved pediatric-onset MS patients and relationship to structural damage and cognitive performance.

Objective: To evaluate resting-state functional connectivity (FC) and relationship to brain volumes and cognition in a sample of cognitively preserved pediatric-onset multiple sclerosis (MS) patients.

Methods: Sixteen cognitively intact pediatric-onset MS patients and 15 healthy age- and sex-matched controls underwent cognitive testing and 3T anatomical and functional MRI. Resting-state FC patterns were examined using region-of-interest-based timeseries correlations.

Results: Compared to controls, pediatric-onset MS patients demonstrated higher FC of the precuneus, particularly with the anterior cingulate cortex (z=4.21, p<.001), frontal medial cortex (z=3.48, p<.001), and cerebellum (z=3.72, p<.001). Greater T2 lesion volume and lower normalized thalamic volume were associated with reduced FC of the thalamus, especially for FC with the right superior occipital region (t=-2.87, p=.0123 and t=2.27, p=.04 respectively). FC of the left frontal medial cortex was negatively correlated with composite cognitive z-score in the pediatric-onset MS group (p<.05).

Conclusions: Greater resting-state FC between posterior and anterior brain regions is present in pediatric-onset MS. With greater disease-related structural pathology, there is a disruption of thalamo-cortical FC. In the absence of actual cognitive impairment, heightened FC of the frontal medial cortex was associated with lower cognitive performance, suggesting that greater functional resources are recruited during resting-state in patients with reduced cognitive efficiency.