Education, and the balance between dynamic and stationary functional connectivity jointly support executive functions in relapsing–remitting multiple sclerosis

Abstract

Graphical network characteristics and nonstationary functional connectivity features, both derived from resting‐state functional magnetic resonance imaging (rsfMRI) data, have been associated with cognitive performance in healthy subjects. How these features jointly relate to cognition in diseased states has not been investigated. In this study, 46 relapsing–remitting multiple sclerosis subjects underwent rsfMRI scans and a focused cognitive battery. With a sliding window approach, we examined six dynamic network features that indicated how connectivity changed over time as well as six measures derived from graph theory to reflect static network characteristics. Multiset canonical correlation analysis (MCCA) was then carried out to investigate the relations between dynamic network features, stationary network characteristics, cognitive testing, demographic, disease severity, and mood. Multiple sclerosis (MS) subjects demonstrated weaker connectivity strength, decreased network density, reduced global changes, but increased changes in interhemispheric connectivity compared to controls. The MCCA model determined that executive functions and processing speed ability measured by Wechsler Adult Intelligence Scale IV (WAIS‐IV) Working Memory Index, WAIS‐IV Processing Speed Index, and the Verbal Fluency Test were positively correlated with education, dynamic connectivity, and static connectivity strength; while poor task switching was correlated with disease severity, psychiatric comorbidities such as depression, anxiety, and fatigue, and static network density. Taken together, our results suggest that better executive functioning in MS requires maintenance of a continued coordination between stationary and dynamic functional connectivity as well as the support of education, and dynamic functional connectivity may provide an additional cognitive biomarker of disease severity in the MS population.

Reduced dynamics of functional connectivity and cognitive impairment in multiple sclerosis

“…The impact of abnormal network dynamics on cognitive impairment is also confirmed by the meta-state analysis, which showed that, compared to CP, CI MS patients had lower number of meta-states and less frequent switching between states, operating over a restricted dynamic range (less distance travelled through connectivity metastates). The notion that reduced network dynamics and reduced time spent in a highly-connected state may help to distinguish patients with a given pathological condition and more severe symptoms is in line with some recent data from patients with schizophrenia 34 and with the preliminary results obtained by MS studies investigating cognitive deficits in single domains, including executive functions 16 and memory. 15 Our study has some limitations.…”

“…10 While these methods were extensively used in studies investigating neuropsychiatric diseases, 13,22 only a few studies have applied these techniques to explore static and dynamic RS FC brain abnormalities and their relationship with deficits in specific cognitive domains in MS patients. [14][15][16] Our sFNC analysis showed that, compared to healthy controls, MS patients had distributed RS FC abnormalities within and between sub-cortical and cognitive/default-mode/visual networks, characterized by both decreased and increased sFNC. Concomitant increase and decrease of sFNC between different brain networks was also found when comparing CI and CP MS patients.…”

“…13 Only a few studies have investigated RS FC dynamic properties in MS patients, describing trends towards abnormal connectivity dynamism in this population. [14][15][16] In this work, we hypothesized that dynamic RS FC analysis may provide novel insights into the mechanisms associated with cognitive impairment in MS patients. Since cognitive impairment is mainly characterized by decreased information processing speed, our a priori hypothesis was that cognitively impaired (CI) MS would show a slower inter-network connectivity than cognitively preserved (CP) MS. To test this hypothesis, we analyzed cognitive and dynamic RS fMRI data collected within a multicenter project by applying a recently developed method, 11 which is based on short time windowed correlations computed on time courses of spatial independent components, and clustering dynamic connectivity patterns using a kmeans approach.…”

Characterizing Rapid Fluctuations of Resting State Functional Connectivity in Demyelinating, Neurodegenerative, and Psychiatric Conditions: From Static to Time-Varying Analysis

“…The large majority of studies assessing TVC in MS patients mainly relied on the use of a priori atlases, such as the Automatic Anatomical Labeling (AAL) (Tzourio-Mazoyer et al, 2002) or the Desikan (Desikan et al, 2006) cortical atlas (Leonardi et al, 2013; Lin et al, 2018; van Geest et al, 2018a,b). Some studies built ad-hoc ROIs centered in critical nodes of large-scale brain networks (Bosma et al, 2018).…”

Both Stationary and Dynamic Functional Interhemispheric Connectivity Are Strongly Associated With Performance on Cognitive Tests in Multiple Sclerosis

“…A few studies have recently demonstrated that dFC is associated with cognitive performance in MS. Performance on processing speed, working memory, and executive function tests has been associated with higher variation of both global and specific (e.g., interhemispheric connections) resting-state functional connectivity (i.e., higher dFC) in MS (33). Another study has reported that greater variability of connectivity within the default mode network is related to better performance in a processing speed task (34).…”