Investigating increased functional connectivity in multiple sclerosis

Increased functional connectivity (FC) is unable to compensate for tissue damage and prevent cognitive dysfunction in patients with multiple sclerosis, according to a study published in the June issue of Radiology.

Deep gray matter is thought to be affected in patients with multiple sclerosis, and previous MRI studies have indicated that significant correlations exist between clinical disability and thalamic ultrastructural changes and atrophy in patients with relapsing-remitting multiple sclerosis. Moreover, researchers have shown that white matter thalamocortical connections are altered in patients with multiple sclerosis. Lead author Francesca Tona, MD, of the Sapienza University of Rome, and colleagues investigated thalamocortical FC by using resting state MRI and evaluated the effect of functional thalamic resting state networks (RSN) on cognitive impairment in patients with relapsing-remitting multiple sclerosis.

The study included 48 patients with relapsing-remitting multiple sclerosis and 24 control subjects who underwent multimodal MRI, including diffusion-tensor imaging, 3D T1-weighted imaging, and functional MRI at rest along with a neuropsychological examination with the Paced Auditory Serial Addition Test (PASAT).

After analyzing the functional MRI data with tools from FMRIB Software Library, the researchers found that the patients showed gray matter and white matter atrophy and diffusion-tensor imaging abnormalities when compared with the control subjects.

Patients exhibited significantly greater synchronization than control subjects in the cerebellum, basal ganglia, hippocampus, cingulum, and temporo-occipital, insular, frontal and parietal cortices. Patients also showed significantly lower synchronization in the thalamus, cerebellum, cingulum, and insular, prefrontal, and parieto-occipital cortices.

In the patients, the PASAT score at three seconds was significantly inversely correlated with the thalamus, cerebellum and some cortical areas in all cerebral lobes. The PASAT score at two seconds correlated even more significantly with all of the previously listed regions as well as the cingulum and the left hippocampus.

“Our results indicate a strict correlation between FC and cognitive performance in patients with relapsing-remitting multiple sclerosis, suggesting that changes in neuroplasticity are unable to prevent the cognitive decline; we cannot, however, establish whether they limit its clinical effects to some extent,” wrote Tona and colleagues. “Further studies that also include patients with other MS phenotypes would lend strength to these findings,” they concluded.