Structural networks involved in attention and executive functions in multiple sclerosis

Sara Llufriu,Nuria Sola-Valls,Magi Andorra,Maria Sepulveda,Elisabeth Solana,Pablo Villoslada,Eloy Martinez-Heras,Alberto Prats-Galino,Albert Saiz,Elena H Martinez-Lapiscina,Yolanda Blanco

doi:10.1016/j.nicl.2016.11.026

Abstract

Attention and executive deficits are disabling symptoms in multiple sclerosis (MS) that have been related to disconnection mechanisms. We aimed to investigate changes in structural connectivity in MS and their association with attention and executive performance applying an improved framework that combines high order probabilistic tractography and anatomical exclusion criteria postprocessing. We compared graph theory metrics of structural networks and fractional anisotropy (FA) of white matter (WM) connections or edges between 72 MS subjects and 38 healthy volunteers (HV) and assessed their correlation with cognition. Patients displayed decreased network transitivity, global efficiency and increased path length compared with HV (p < 0.05, corrected). Also, nodal strength was decreased in 26 of 84 gray matter regions. The distribution of nodes with stronger connections or hubs of the network was similar among groups except for the right pallidum and left insula, which became hubs in patients. MS subjects presented reduced edge FA widespread in the network, while FA was increased in 24 connections (p < 0.05, corrected). Decreased integrity of frontoparietal networks, deep gray nuclei and insula correlated with worse attention and executive performance (r between 0.38 and 0.55, p < 0.05, corrected). Contrarily, higher strength in the right transverse temporal cortex and increased FA of several connections (mainly from cingulate, frontal and occipital cortices) were associated with worse functioning (r between − 0.40 and − 0.47, p < 0.05 corrected). In conclusion, structural brain connectivity is disturbed in MS due to widespread impairment of WM connections and gray matter structures. The increased edge connectivity suggests the presence of reorganization mechanisms at the structural level. Importantly, attention and executive performance relates to frontoparietal networks, deep gray nuclei and insula. These results support the relevance of network integrity to maintain optimal cognitive skills.

Highlights

Cognitive dysfunction is present in 40%–70% of patients with multiple sclerosis (MS) (Amato et al, 2010) predominantly affecting attention and executive functions, information processing speed and episodic memory (Rocca et al, 2015)
Cognitive dysfunction in MS has been associated with disconnection mechanisms related to focal lesions and diffuse microstructural damage in strategic white matter (WM) tracts involved in cognitive performance, in addition to gray matter (GM) impairment (Bozzali et al, 2013; Calabrese et al, 2009; Harrison et al, 2015; Llufriu et al, 2014; Preziosa et al, 2016)
We aimed to investigate changes in structural connectivity in patients with MS and their association with attention and executive functioning applying an improved framework for tractography reconstruction by combining iFOD2 and automatic postprocessing based on AEC (Martínez-Heras et al, 2015)

Summary

Introduction

Cognitive dysfunction is present in 40%–70% of patients with multiple sclerosis (MS) (Amato et al, 2010) predominantly affecting attention and executive functions, information processing speed and episodic memory (Rocca et al, 2015). Brain functional modifications in task-based studies seem to drive compensatory mechanisms at the earliest stages of disease, when structural damage is low, with increased cortical recruitment probably contributing to the maintenance of a normal level of cognitive performance. In later phases, those changes are lost or exhausted leading to cognitive dysfunction (Rocca et al, 2015)

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