Structural and functional abnormalities in the frontal cortico-subcortical network are associated with fatigue and worse dual-task performance of walking and cognition in patients with progressive multiple sclerosis (MS), according to a new study published in the Journal of Neurology.

“Our findings further support that the investigated network may have a pathogenic role for both these clinical manifestations. It may represent a target for novel therapeutic strategies aimed at limiting the detrimental effects of fatigue and worse dual-task performances,” Massimo Filippi, MD, of the Vita-Salute San Raffaele University in Milan, Italy, and colleagues noted.

Notably, the observed patterns differ based on whether or not fatigue is present, the authors added.

Continue Reading

Read more about MS symptoms

The investigators set out to explore the link between fatigue, dual-task performance, and structural and functional abnormalities in progressive MS. In doing so, they analyzed 57 patients with progressive MS and 10 healthy volunteers. 

The researchers analyzed the participants’ brain 3 T structural and functional magnetic resonance imaging sequences, Modified Fatigue Impact Scale (MFIS) scores, and dual-task motor and cognitive performances. 

Most patients with MS (65%) had an MFIS score of 38 or more and were fatigued. Patients with progressive MS had significantly worse dual-task performance compared to healthy controls, whether or not they were fatigued. 

The team identified predictors of fatigue and its severity as being a higher Expanded Disability Status Scale (EDSS) score, lower resting state effective connectivity from the left caudate nucleus to left dorsolateral prefrontal cortex, lower fractional anisotropy between the left caudate nucleus and left thalamus, higher mean diffusivity between the right caudate nucleus and right thalamus, and longer disease duration.

Factors that predicted worse dual-task performances were microstructural abnormalities in connections in thalami, caudate nuclei, and dorsolateral prefrontal cortex, lower resting state effective connectivity from the left caudate nucleus to left dorsolateral prefrontal cortex in fatigued patients, and higher resting state effective connectivity from the left dorsolateral prefrontal cortex to the right dorsolateral prefrontal cortex in nonfatigued patients. Other factors included a higher EDSS score, lower cortical volume, and higher white matter lesion volume.


Preziosa P, Rocca MA, Pagani E, et al. Structural and functional magnetic resonance imaging correlates of fatigue and dual-task performance in progressive multiple sclerosis. J Neurol. Published online November 27, 2022. doi:10.1007/s00415-022-11486-0