Abnormalities of resting state functional connectivity are related to sustained attention deficits in MS.

Loitfelder, Marisa; Filippi, Massimo; Rocca, Mara; Valsasina, Paola; Ropele, Stefan; Jehna, Margit; Fuchs, Siegrid; Schmidt, Reinhold; Neuper, Christa; Fazekas, Franz; Enzinger, Christian · 2012 · DOAJ

DOI: 10.1371/journal.pone.0042862

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Summary

This study investigates the relationship between resting-state functional connectivity (RS-FC) and sustained attention deficits in patients with multiple sclerosis (MS). While cognitive dysfunction is a significant aspect of MS, conventional task-related fMRI often suffers from floor and ceiling effects in impaired patient groups. To address this, the authors utilized RS-fMRI, which assesses network abnormalities without demanding specific tasks, focusing on the anterior cingulate cortex (ACC) as a seed region due to its established role in executive functioning and attention. The researchers analyzed 3 Tesla fMRI data from 31 MS patients (including clinically isolated syndrome, relapsing-remitting, and secondary progressive subtypes) and 31 age- and gender-matched healthy controls. Participants underwent extensive neuropsychological testing, including the Paced Auditory Serial Addition Test (PASAT) and Symbol Digit Modalities Test (SDMT). The study employed a novel approach using rest phases from existing block-design fMRI data to calculate RS-FC. Data preprocessing included realignment, normalization, band-pass filtering, and regression of motion and physiological noise signals. Statistical analyses compared group-level FC maps and correlated FC strength with cognitive performance metrics. Results indicated that both groups exhibited significant RS-FC between the ACC and regions such as the posterior cingulate cortex, insula, caudate, and cerebellum. However, MS patients demonstrated increased FC between the ACC and the left angular gyrus, left posterior cingulate cortex, and right postcentral gyrus compared to controls. Crucially, better cognitive performance in MS patients was positively correlated with increased FC to the cerebellum, middle temporal gyrus, occipital pole, and angular gyrus. Conversely, poorer performance was associated with negative correlations in frontal and striatal regions. These findings suggest that the observed connectivity changes in MS patients represent adaptive neural reorganization rather than mere degradation. The study concludes that abnormalities in RS-FC within the sustained attention network are directly related to cognitive deficits in MS. The increased connectivity observed in patients likely reflects compensatory mechanisms to maintain function despite disease-related damage. These results extend previous task-based fMRI findings, demonstrating that RS-fMRI can effectively map functional network alterations and provide deeper insights into the neural mechanisms underlying cognitive dysfunction in MS. This approach offers a sensitive, objective tool for assessing brain function and potentially monitoring therapeutic interventions.

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• cognitive impairment