Structural networks involved in attention and executive functions in multiple sclerosis

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.

Changes of white matter integrity and structural network connectivity in nondemented cerebral small‐vessel disease

“…Second, reactive structural plasticity such as gliosis is a common histopathological change in CSVD, 33 which may resulted in strengthened interhemispherical connections, like in early multiple sclerosis. 34,35 The observation of increased small-worldness in our study also indicate compensatory reorganization of the structural network. Although exhibiting widespread WM integrity deterioration, the CSVD patients enrolled in this study had very mild cognitive impairment, corresponding to our reported mild structural network alterations.…”

“…Incomplete infarcts in CSVD may result in the observation of relatively intact local network characteristics in our study. Second, reactive structural plasticity such as gliosis is a common histopathological change in CSVD, which may resulted in strengthened interhemispherical connections, like in early multiple sclerosis . The observation of increased small‐worldness in our study also indicate compensatory reorganization of the structural network.…”

Gray matter integrity predicts white matter network reorganization in multiple sclerosis

“…Measures of path distance have been shown previously to be increased in patients compared to healthy controls (Llufriu et al, 2017), probably a direct consequence of focal tissue damage. Higher eccentricity in a network indicates a disruption of information flow, which is rerouted via longer pathways.…”

“…Further, lower global and local efficiency, as well as clustering, were related to worse attention and information processing capacities (Shu et al, 2016). In a further study, a decrease in clustering and global efficiency was observed in patients with RRMS compared to healthy controls, while the distance measure path length was increased (Llufriu et al, 2017). As a first step to investigate network alterations in relation to disease progression, groups of patients with different disease durations were investigated (Fleischer et al, 2017).…”

Complex Brain Network Analysis and Its Applications to Brain Disorders: A Survey

“…In addition, MS patients exhibited increased path length compared with HCs, and MD-MS patients showed increased local path length in the right hippocampus and right amygdala compared with ND-MS patients and HCs. To investigate changes in structural connectivity in MS, Llufriu et al [133] used FA values as connectivity strength between brain regions to construct structural brain networks of 72 MS patients and 38 HCs. In their study, compared with HCs, MS patients showed decreased transitivity and global efficiency and increased path length.…”