# Contribution of Gray and White Matter Abnormalities to Cognitive Impairment in Multiple Sclerosis
## 3 Discussion  
The current study revealed several main findings. First, MS patients exhibited worse performance on the SDMT and PASAT-3\" compared with HCs. We found extensive WM damage, including cortical and subcortical GM atrophy in the right insula, middle frontal gyrus, inferior frontal gyrus and left cingulate gyrus in MS patients compared with HCs. In addition, CI-MS patients exhibited worse performance on the Auditory Verbal Learning Test (AVLT), Verbal Fluency Test (VFT), PASAT-3\", Brief Visuospatial Memory Test (BVMT), and Trail making test (TMT) compared with CP-MS patients. CI-MS patients showed a widespread reduction in FA values in many WM tracts throughout the skeletons, compared with CP-MS patients. The results also revealed regional GM atrophy in several regions, including the right temporal lobe, left insula and bilateral caudate. The current results revealed a significant difference in SDMT and PASAT-3\" performance between MS and HC, which primarily reflects information processing speed and working memory performance. This finding is consistent with previous reports [1; 16]. Moreover, we found widespread WM impairment, as well as cortical and subcortical GM loss in a number of areas, including the insula, frontal gyrus and cingulate gyrus, in accord with a number of previous studies [10; 11; 12; 17; 18; 19; 20]. Both WM and GM abnormalities are known to be involved in MS.  
Further analyses revealed significant differences in verbal fluency, speed of information processing, executive function, and spatial memory between CI-MS and CP-MS patients, in accord with previous studies [10; 21]. In addition, the CI group exhibited widespread WM microstructure dysfunction compared with the CP group in a range of brain regions, including the corpus callosum, cerebellar peduncle, corona radiata, optic radiation, superior longitudinal fasciculus, the anterior limb of the internal capsule, and the cingulate. The corpus callosum has previously been implicated in the \begin{table}
\begin{tabular}{l c c c c c c} \hline \hline \multirow{2}{*}{**Brain Region**} & \multirow{2}{*}{**Number of Voxels (mm3)**} & \multicolumn{2}{c}{**Peak MNI Coordinate**} & \multicolumn{2}{c}{**Brodmann**} & \multirow{2}{*}{\(T\) **Value**} \\ \cline{3-3} \cline{5-6}  & & \(x\) & \(y\) & \(z\) & \multicolumn{1}{c}{**Area**} & \\ \hline Right temporal lobe & 117 & 42 & 18 & \(-\)22 & 38 & 7.29 \\ Left insula & 70 & \(-\)31 & 19 & \(-\)4 & 13 & 7.30 \\ Right caudate & 137 & 12 & 16 & 10 & NA & 6.66 \\ Left caudate & 74 & \(-\)13 & 10 & 16 & NA & 6.65 \\ \hline \hline \end{tabular} Each cluster represents the extension where local maxima are located, along with the MNI coordinates, and the \(T\) values of the most significant voxel are reported. A threshold of \(p\) < 0.05 is set for the data, and the data are corrected using the false discovery rate (FDR). MNI = Montreal Neurological Institute; FWE = family-wise error; NA = not applicable.  
\end{table} 
Table 4: The decreased volumes of GM in CI patients compared with the CP group (\(p_{FWE\_correlation}\) < 0.05). Figure 4: Statistical parametric mapping (SPM) regions exhibiting decreased gray matter (GM) volume in CI patients compared with CP patients (\(p\) < 0.05, FWE corrected for multiple comparisons). SPM regions exhibiting significant GM loss including right temporal lobe, left insula and bilateral caudate (**A**); left insula (**B**); bilateral caudate (**C**). speed of information processing, executive function, and verbal fluency [22]. In addition, damage to the optic radiation and superior longitudinal fasciculus have been associated with spatial memory deficits [23; 24]. [PERSON] et al. reported a 76% decrease in FA in the WM of CI patients, and a 49% FA decrease in the WM of CP patients. On the basis of these results, the authors speculated that WM damage was related to CI-MS [10]. The current results further support the notion that WM damage is associated with cognitive dysfunction in MS.