Neuroimaging Correlates of Cognitive Dysfunction in Adults with Multiple Sclerosis

Abstract

Cognitive impairment is a frequent and meaningful symptom in multiple sclerosis (MS), caused by the accrual of brain structural damage only partially counteracted by effective functional reorganization. As both these aspects can be successfully investigated through the application of advanced neuroimaging, here, we offer an up-to-date overview of the latest findings on structural, functional and metabolic correlates of cognitive impairment in adults with MS, focusing on the mechanisms sustaining damage accrual and on the identification of useful imaging markers of cognitive decline.

Keywords: atrophy; cognitive dysfunction; magnetic resonance imaging; multiple sclerosis; neuroimaging; positron emission tomography; sodium.

Figure 1

Diffusion basis spectrum imaging (DBSI) maps for the investigation of tissue properties. Selected T2- and T1-weighted images, together with DBSI-derived maps from a patient diagnosed with multiple sclerosis. Variations of each metric in normal appearing tissue in comparison with lesions (indicated by arrows) can be appreciated. The color bar expresses each DBSI-metric adimensional unit of measure. Reprinted from Brain, Vol. 144, Issue 1, P213–223, 12 February 2021. Schiavi S. et al. “Non-invasive quantification of inflammation, axonal and myelin injury in multiple sclerosis” [42]. Copyright: © 2021, with permission from Oxford University Press.

Figure 2

Multiplanar representation of single-slab 3D double-inversion recovery images of a patient with MS. (A) Sagittal view of a juxtacortical lesion (arrow) in the frontal vertex. (B) Coronal orientation: same wedge-shaped juxtacortical lesion (white arrow), as well as a mixed grey matter–white matter (type I) lesion (arrowhead) near the frontal operculum and a smaller juxtacortical lesion frontomedially (green arrow). (C) Same two juxtacortical lesions as shown in (A,B), in the axial orientation. Reprinted from The Lancet Neurology, Vol. 7, Issue 9, P841–851, 1 September 2008 [60]. Copyright: © 2021, with permission from Elsevier.

Figure 3

Flowchart of brain network reconstruction. For each subject, (A) T1-weighted image is segmented into grey matter (B) and white matter (C). The grey matter segmentation is parcellated into cortical and deep grey matter regions (B), which serve as network nodes (D) in the subsequent network-based analysis. From a diffusion-weighted image (DWI) (E), voxel-wise fiber orientation distribution (FOD) (F) is estimated and whole-brain tractography undertaken (G), with the white matter segmentation (C) used to prevent this from spilling into grey matter. Finally, nodes and tractogram are modelled into a network (H). Connections are weighted by the sum of the pairwise streamline weights. Reprinted from JNNP, Vol. 90, Issue 2, 01 February 2019 [91]. Copyright: © 2021, with permission from BMJ Publishing Group Ltd.

Figure 4

Cerebellar functional connectivity in multiple sclerosis. Cerebellar functional connectivity modification in patients with multiple sclerosis compared to controls, without taking into account (A) and after controlling (B) for cerebellar structural damage. Clusters of significant functional connectivity decrease are shown in red, while clusters of significant functional connectivity increase are presented in blue, superimposed on a standard 3D rendering of a brain volume in the Montreal Neurological Institute space. Reprinted from JOON, Vol. 265, Issue 10, P2260–2266, October 2018 [111]. Copyright: © 2021, with permission from Springer Nature.

Figure 5

An overview of positron emission tomography (PET) targets and tracers. A schematic representation of the main targets of PET imaging in multiple sclerosis (gray boxes), along with the respective tracers (in red). Reprinted from EJNMMI Radiopharmacy and Chemistry Vol. 4, Issue 1, P6, 8 April 2019 [120]. Copyright: © 2021, with permission from Springer Open.

Figure 6

Sodium maps. Mean sodium MRI maps for multiple sclerosis patients (left column) and controls (right column). In the first row is displayed the total sodium concentration (A,B), while in the middle and last rows, the intracellular sodium concentration (C,D) and the intracellular sodium volume fraction (indirect measure of extracellular sodium concentration) (E,F) are shown. Reprinted from Brain, Vol. 139, Issue 3, P 795–806, 20 January 2016 [167]. Copyright: © 2021] with permission from Oxford University Press.