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Abstract
Objective: To assess the contribution of microstructural normal-appearing white matter (NAWM) damage to social cognition impairment, specifically in the theory of mind (ToM), in multiple sclerosis (MS).
Methods: We enrolled consecutively 60 patients with MS and 60 healthy controls (HC) matched on age, sex, and education level. All participants underwent ToM testing (Eyes Test, Videos Test) and 3T brain MRI including conventional and diffusion tensor imaging sequences. Tract-based spatial statistics (TBSS) were applied for whole-brain voxel-wise analysis of fractional anisotropy (FA) and mean diffusivity (MD) on NAWM.
Results: Patients with MS performed worse on both tasks of ToM compared to HC (Eyes Test 58.7 ± 13.8 vs 81.9 ± 10.4, p < 0.001, Hedges g −1.886; Videos Test 75.3 ± 9.3 vs 88.1 ± 7.1, p < 0.001, Hedges g −1.537). Performance on ToM tests was correlated with higher values of FA and lower values of MD across widespread white matter tracts. The largest effects (≥90% of voxels with statistical significance) for the Eyes Test were body and genu of corpus callosum, fornix, tapetum, uncinate fasciculus, and left inferior cerebellar peduncle, and for the Videos Test genu and splenium of corpus callosum, fornix, uncinate fasciculus, left tapetum, and right superior fronto-occipital fasciculus.
Conclusions: These results indicate that a diffuse pattern of NAWM damage in MS contributes to social cognition impairment in the ToM domain, probably due to a mechanism of disconnection within the social brain network. Gray matter pathology is also expected to have an important role; thus further research is required to clarify the neural basis of social cognition impairment in MS.
GLOSSARY
- BDI=
- Beck Depression Inventory;
- DTI=
- diffusion tensor imaging;
- EDSS=
- Expanded Disability Status Scale;
- FA=
- fractional anisotropy;
- FDR=
- false discovery rate;
- FLAIR=
- fluid-attenuated inversion recovery;
- FSL=
- FMRIB Software Library;
- FWE=
- family-wise error;
- GM=
- gray matter;
- HC=
- healthy control;
- MD=
- mean diffusivity;
- MFIS=
- Modified Fatigue Impact Scale;
- MS=
- multiple sclerosis;
- NAWM=
- normal-appearing white matter;
- TBSS=
- tract-based spatial statistics;
- TE=
- echo time;
- ToM=
- theory of mind;
- TR=
- repetition time;
- WM=
- white matter
Footnotes
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Supplemental data at Neurology.org
Editorial, page 16
- Received November 23, 2016.
- Accepted in final form March 14, 2017.
- © 2017 American Academy of Neurology
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