Regional Brain Atrophy and Functional Connectivity Changes Related to Fatigue in Multiple Sclerosis

Abstract

Fatigue is one of the most frequent symptoms in multiple sclerosis (MS), and recent studies have described a relationship between the sensorimotor cortex and its afferent and efferent pathways as a substrate of fatigue. The objectives of this study were to assess the neural correlates of fatigue in MS through gray matter (GM) and white matter (WM) atrophy, and resting state functional connectivity (rs-FC) of the sensorimotor network (SMN). Eighteen healthy controls (HCs) and 60 relapsing-remitting patients were assessed with the Fatigue Severity Scale (FSS). Patients were classified as fatigued (F) or nonfatigued (NF). We investigated GM and WM atrophy using voxel-based morphometry, and rs-FC changes with a seed-based method and independent component analysis (ICA). F patients showed extended GM and WM atrophy focused on areas related to the SMN. High FSS scores were associated with reductions of WM in the supplementary motor area. Seed analysis of GM atrophy in the SMN showed that HCs presented increased rs-FC between the primary motor and somatosensory cortices while patients with high FSS scores were associated with decreased rs-FC between the supplementary motor area and associative somatosensory cortex. ICA results showed that NF patients presented higher rs-FC in the primary motor cortex compared to HCs and in the premotor cortex compared to F patients. Atrophy reduced functional connectivity in SMN pathways and MS patients consequently experienced high levels of fatigue. On the contrary, NF patients experienced high synchronization in this network that could be interpreted as a compensatory mechanism to reduce fatigue sensation.

Parkinson's disease‐related fatigue: A case definition and recommendations for clinical research

“…Another study also showed no difference in 18 F‐dopa uptake between 10 fatigued PD subjects and 10 nonfatigued PD subjects but revealed serotonin transporter binding in the caudate, putamen, ventral striatum, and thalamus was decreased in fatigued compared with nonfatigued patients . The role of other neurotransmitter systems (eg, norepinephrine, acetylcholine GABA, glutamate), morphologic changes in gray and white matter, and regional brain activity and functional connectivity have yet to be explored in PD‐related fatigue but are associated with fatigue in other neurologic disorders and should be pursued …”

Brain Plasticity Effects of Neuromodulation Against Multiple Sclerosis Fatigue

“…This phenomenon has been attributed to a failure of intracortical inhibition (ICI) in frontal and M1 areas, both before and after fatiguing exercises ( 4 ). Furthermore, structural and functional data report a parietal involvement in MS fatigue symptoms ( 7 – 9 ), with indications of a reduced primary somatosensory area (S1) excitability ( 10 , 11 ), and tDCS has been reported to enhance parieto-frontal projections ( 12 ). Also, in previous works of ours, we noticed signs of impaired communication between S1 and M1 ( 13 ).…”

Altered neural signatures of interoception in multiple sclerosis

“…b): Links indicate interregional connectivity. Indeed, the heterogeneous patterns of functional connectivity alterations in MS include abnormalities between interoceptive areas, such as the ACC and the insula(Faivre et al, 2012;Rocca et al, 2015;Roosendaal et al, 2010), alongside disruptions in relevant anatomical pathwaysfor example, the ACC white matter bundle within the left cingulate fasciculus (CruzGomez, Ventura Campos, Belenguer, Avila, & Forn, 2013;Pardini et al, 2015). Colors indicate statistically significant differences (p < .05; green = interoception > mind wandering; red = MS patients > controls; black = no significant differences).…”