Reduced rich-club connectivity is related to disability in primary progressive MS

Abstract

Objective:To investigate whether the structural connectivity of the brain's rich-club organization is altered in patients with primary progressive MS and whether such changes to this fundamental network feature are associated with disability measures.Methods:We recruited 37 patients with primary progressive MS and 21 healthy controls for an observational cohort study. Structural connectomes were reconstructed based on diffusion-weighted imaging data using probabilistic tractography and analyzed with graph theory.Results:We observed the same topological organization of brain networks in patients and controls. Consistent with the originally defined rich-club regions, we identified superior frontal, precuneus, superior parietal, and insular cortex in both hemispheres as rich-club nodes. Connectivity within the rich club was significantly reduced in patients with MS (p = 0.039). The extent of reduced rich-club connectivity correlated with clinical measurements of mobility (Kendall rank correlation coefficient τ = −0.20, p = 0.047), hand function (τ = −0.26, p = 0.014), and information processing speed (τ = −0.20, p = 0.049).Conclusions:In patients with primary progressive MS, the fundamental organization of the structural connectome in rich-club and peripheral nodes was preserved and did not differ from healthy controls. The proportion of rich-club connections was altered and correlated with disability measures. Thus, the rich-club organization of the brain may be a promising network phenotype for understanding the patterns and mechanisms of neurodegeneration in MS.

Rich-club in the brain’s macrostructure: Insights from graph theoretical analysis

“…Moreover, patients with generalized tonic-clonic seizures have reduced rich-club connectivity, which is associated with longer durations of illness and seizure frequencies [104] . Structural connectivity of rich-club regions is decreased in patients with multiple sclerosis, in whom decreased rich-club connectivity is associated with mobility, hand function, information processing speed [105] , and cognitive impairments [106] . In patients with traumatic brain injury (TBI), the strength of local connections is increased, but rich-club connectivity is decreased [107] .…”

Impaired rich club and increased local connectivity in children with traumatic brain injury: Local support for the rich?

“…Crossley et al () showed that because of this high value yet high cost, hubs are more likely to be affected compared to other brain regions in patients with brain disorders. Their evidence is strengthened by studies in different clinical populations, for example, in multiple sclerosis (Stellmann et al, ), schizophrenia (van den Heuvel et al, ), and attention‐deficit hyperactivity disorder (Ray et al, ), all showing reduced rich club connectivity.…”

Modeling Resilience to Damage in Multiple Sclerosis: Plasticity Meets Connectivity

“…Notably, progressive MS represents a useful model to test this hypothesis. Accordingly, in progressive MS, reduced rich club connectivity and a relative increase of local connectivity have been demonstrated [96]. Consistently, absent LTP induction and pathologically enhanced synaptic upscaling have been revealed in this MS phenotype [57,97,98].…”