3.1 Baseline clinical characteristics
Table 1 provides an overview of each participant group's demographics. For this study, we invited 30 individuals diagnosed with MS and 30 healthy control participants to participate. The MS patients collected in this study had a relatively light disease burden (EDSS average of 1.67) and mild cognitive impairment (MMSE average of 27.87, MOCA average of 25.03). The proportion of patients receiving disease modification therapy is relatively high, at 90%. Table 2 shows patients' mean brain volume and cortical thickness in each group. The differences in GMV (P=0.016), WMV (P=0.008), CSFV (P=0.013), and cortical thickness (P=0.000) between the two groups were statistically significant.
Table-1. Demographics of healthy controls and patients with multiple sclerosis.
|
MS(n=30)
|
HCs(n=30)
|
P
|
Gender (male/female)
|
3/27
|
7/23
|
0.299
|
Age(year)
|
34.06±7.40
|
31.30±7.33
|
0.151
|
Disease duration (year)
|
3.87±3.60
|
-
|
-
|
Annual recurrence rate
|
0.42±0.53
|
-
|
-
|
EDSS
|
1.67±1.60
|
-
|
-
|
MMSE
|
27.87±2.85
|
-
|
-
|
MoCA
|
25.03±3.59
|
-
|
-
|
HAMA
|
9.27±7.77
|
-
|
-
|
HAMD
|
7.70±6.39
|
-
|
-
|
T25FW (s, n=28)
|
5.62±2.68
|
-
|
-
|
%(no.) of patients on DMTs
|
90(27)
|
-
|
-
|
Note: Data are shown as mean±SD.
Abbreviation: DMTs: disease modeling treatments
*P value: <0.05
Table-2. Mean TIV, WMV, GMV, CSFV, and cortical thickness values of MS patients and HCs.
MS(n=30)
|
HC(n=30)
|
P
|
1324.68±120.95
|
1338.07.50±108.96
|
0.654
|
591.95±55.07
|
622.46±39.00
|
0.016*
|
442.18±60.73
|
477.76±37.65
|
0.008*
|
290.56±85.88
|
237.84±73.03
|
0.013*
|
2.26±0.11
|
2.37±0.07
|
0.000*
|
Note: Data are shown as mean±SD.
Abbreviation: TIV: Total intracranial volume, WMV: White matter volume, GMV: Gray Matter volume, CSFV: Cerebrospinal fluid volume.
*P value: <0.05
3.2 VBM
Figure 3 shows the areas with significant differences in gray matter volume between groups. Compared with HCs, the areas of volume reduction in the MS group were mainly located in the deep gray matter, including the bilateral thalamus, putamen, globus pallidus, caudate nucleus, hippocampus, and insula, with a small portion located in the cortical gray matter, including parts of the parahippocampal gyrus and temporal lobe (Table 3 and Figure 4).
Table-3. Clusters with significantly reduced GM volume in the MS group
Cluster size N voxel
|
P(FWE-Corr)
|
Peak T
|
MNI coordinates
|
Anatomical area
|
x
|
y
|
z
|
15156
|
0.000*
|
6.979
|
22.5
|
-28.5
|
1.5
|
Thalamus_R
|
|
|
6.917
|
-18
|
-10.5
|
3
|
Thalamus_L
|
|
|
6.901
|
18
|
-6
|
4.5
|
Pallidus _R
|
Note: Corrected P [FWE] < 0.05 at the cluster level.
L left; R: right; FWE: Family-Wise Error; MNI: Montreal Neurological Institute.
3.3 SBM
Figure 5 shows the areas with differences in cortical thickness between groups. Compared with HCs, the cortical thickness in the MS group decreased in the bilateral transverse and inferior temporal gyrus, bilateral posterior central gyrus, bilateral fusiform gyrus, right parahippocampal gyrus, right lingual gyrus, right tail of the middle frontal gyrus, right superior marginal gyrus, right superior temporal gyrus, left anterior central gyrus, left posterior cingulate gyrus, and left paracentral lobule (Tables 4).
Table-4. Clusters with significantly reduced cortical thickness in the MS group.
cluster size N voxel
|
P(FWE-Corr)
|
Peak T
|
MNI coordinates
|
Anatomical region(vertices)
|
x
|
y
|
z
|
515
|
0.000*
|
5.13
|
53
|
8
|
-33
|
Temporal_Mid_R
|
|
|
4.95
|
49
|
0
|
-34
|
Temporal_Inf_R
|
|
|
4.13
|
22
|
-21
|
-22
|
ParaHippocampal_R
|
810
|
0.000*
|
4.95
|
-52
|
-13
|
-19
|
Temporal_Mid_L
|
|
|
4.87
|
-55
|
-5
|
-31
|
Temporal_Inf_L
|
|
|
4.44
|
-59
|
-57
|
6
|
Temporal_Mid_L
|
582
|
0.000*
|
4.94
|
-54
|
-11
|
23
|
Postcentral_L
|
|
|
4.14
|
-60
|
-21
|
24
|
Postcentral_L
|
|
|
3.98
|
-60
|
5
|
15
|
Postcentral_L
|
212
|
0.003*
|
4.86
|
-42
|
-62
|
-21
|
Fusiform_L
|
308
|
0.000*
|
4.84
|
42
|
-43
|
-19
|
Fusiform_R
|
|
|
4.12
|
29
|
-61
|
-15
|
Fusiform_R
|
|
|
4.1
|
37
|
-62
|
-18
|
Fusiform_R
|
259
|
0.001*
|
4.77
|
-8
|
-23
|
58
|
Paracentral_Lobule_L
|
|
|
4.39
|
-12
|
-35
|
51
|
Paracentral_Lobule_L
|
257
|
0.001*
|
4.69
|
44
|
1
|
34
|
Postcentral_R
|
|
|
3.65
|
39
|
10
|
40
|
Frontal_Mid_2_R
|
395
|
0.000*
|
4.67
|
49
|
-17
|
-15
|
Temporal_Mid_R
|
|
|
4.55
|
55
|
-27
|
-2
|
Temporal_Mid_R
|
|
|
3.88
|
48
|
-30
|
-8
|
Temporal_Mid_R
|
253
|
0.001*
|
4.51
|
13
|
-60
|
3
|
Lingual_R (aal3v1)
|
|
|
3.46
|
25
|
-49
|
-8
|
Lingual_R (aal3v1)
|
370
|
0.000*
|
4.51
|
-10
|
2
|
40
|
Cingulate_Mid_L (aal3v1)
|
|
|
3.64
|
-9
|
12
|
48
|
Supp_Motor_Area_L (aal3v1)
|
|
|
3.64
|
-3
|
-32
|
31
|
Cingulate_Post_L (aal3v1)
|
986
|
0.000*
|
4.43
|
40
|
-31
|
39
|
SupraMarginal_R (aal3v1)
|
|
|
4.33
|
42
|
-40
|
38
|
SupraMarginal_R (aal3v1)
|
260
|
0.001*
|
3.98
|
56
|
-35
|
18
|
Temporal_Sup_R (aal3v1)
|
|
|
3.71
|
58
|
-42
|
14
|
Temporal_Sup_R (aal3v1)
|
|
|
3.61
|
61
|
-37
|
26
|
SupraMarginal_R (aal3v1)
|
143
|
0.024*
|
3.84
|
-44
|
-20
|
46
|
Postcentral_L (aal3v1)
|
|
|
3.51
|
-54
|
-17
|
51
|
Postcentral_L (aal3v1)
|
Note: Corrected P [FWE] < 0.05 at the cluster level. L: left; R: right.
3.4 Correlation between regional gray matter volume and clinical Scale
The brain regions that differed between the MS and HC groups were used as ROIs, and the gray matter volumes corresponding to the ROIs of the subjects were extracted. The gray matter volume was analyzed by partial correlation with EDSS, MMSE, MoCA, T25FW, HAMA, and HAMD. The correlation analysis showed a negative correlation between the caudate nucleus volume and the EDSS score (R=-0.415, P=0.031) (Table 5).
3.5 Correlation between regional cortical thickness and clinical Scale
Similarly, cortical thickness was analyzed by partial correlation with clinical scales. The correlation analysis showed a positive correlation between the right parahippocampal gyrus and HAMA score (R=0.392, P=0.039). The right central posterior gyrus positively correlates with MMSE and MOCA (the former R=0.433, P=0.021; the latter R=0.431, P=0.022). The left paracentral lobule positively correlates with the MOCA score (R=0.389, P=0.041) (Table 6).
Table 5. Correlation analysis between differential brain area volume and clinical scales
|
EDSS
|
|
MMSE
|
|
MOCA
|
|
T25FW
|
|
HAMA
|
|
HAMD
|
|
|
R
|
P
|
R
|
P
|
R
|
P
|
R
|
P
|
R
|
P
|
R
|
P
|
GMV
|
-0.148
|
0.460
|
0.406
|
0.036
|
0.324
|
0.099
|
-0.299
|
0.130
|
0.022
|
0.914
|
-0.22
|
0.269
|
Thalamus
|
-0.224
|
0.261
|
-0.032
|
0.875
|
-0.078
|
0.701
|
-0.107
|
0.594
|
0.195
|
0.330
|
-0.056
|
0.780
|
Putamen
|
-0.275
|
0.166
|
-0.100
|
0.618
|
-0.007
|
0.972
|
-0.070
|
0.728
|
0.183
|
0.362
|
0.077
|
0.702
|
Parahippocampal
|
-0.084
|
0.676
|
0.161
|
0.423
|
0.050
|
0.803
|
0.165
|
0.411
|
0.112
|
0.577
|
0.132
|
0.512
|
Hippocampus
|
-0.188
|
0.349
|
0.115
|
0.566
|
0.069
|
0.731
|
-0.022
|
0.915
|
0.123
|
0.540
|
0.072
|
0.721
|
Insula
|
0.007
|
0.971
|
0.195
|
0.329
|
0.144
|
0.475
|
0.167
|
0.406
|
0.320
|
0.104
|
0.360
|
0.065
|
Caudate
|
-0.415
|
0.031*
|
-0.043
|
0.831
|
-0.074
|
0.714
|
-0.280
|
0.158
|
0.241
|
0.227
|
0.019
|
0.927
|
Pallidum
|
0.134
|
0.505
|
-0.067
|
0.739
|
-0.266
|
0.181
|
0.188
|
0.349
|
-0.008
|
0.968
|
-0.065
|
0.747
|
*P value: <0.05
Table 6. Correlation analysis between differential brain area cortical thickness and clinical scales
|
EDSS
|
|
MMSE
|
|
MOCA
|
|
T25FW
|
|
HAMA
|
|
HAMD
|
|
|
R
|
P
|
R
|
P
|
R
|
P
|
R
|
P
|
R
|
P
|
R
|
P
|
Cortical thickness
|
-0.094
|
0.633
|
0.276
|
0.156
|
0.306
|
0.113
|
0.144
|
0.465
|
0.313
|
0.105
|
0.142
|
0.470
|
L_inferiortemporal
|
-0.029
|
0.885
|
0.134
|
0.497
|
0.235
|
0.228
|
0.295
|
0.127
|
0.110
|
0.576
|
-0.061
|
0.759
|
R_inferiortemporal
|
-0.157
|
0.426
|
0.133
|
0.499
|
0.156
|
0.427
|
0.118
|
0.551
|
0.215
|
0.272
|
0.156
|
0.429
|
R_parahippocampal
|
-0.145
|
0.462
|
0.088
|
0.654
|
0.131
|
0.505
|
-0.091
|
0.643
|
0.392
|
0.039*
|
0.295
|
0.127
|
L_fusiform
|
-0.233
|
0.232
|
0.131
|
0.508
|
0.306
|
0.113
|
-0.007
|
0.971
|
0.360
|
0.060
|
0.096
|
0.627
|
R_fusiform
|
-0.042
|
0.83
|
0.130
|
0.510
|
0.170
|
0.388
|
0.075
|
0.703
|
0.251
|
0.198
|
0.201
|
0.305
|
L_postcentral
|
-0.203
|
0.299
|
0.289
|
0.135
|
0.307
|
0.112
|
0.035
|
0.86
|
0.170
|
0.388
|
-0.158
|
0.422
|
R_postcentral
|
-0.100
|
0.614
|
0.433
|
0.021*
|
0.431
|
0.022*
|
0.199
|
0.309
|
0.223
|
0.255
|
0.038
|
0.846
|
L_middletemporal
|
0.063
|
0.751
|
0.125
|
0.526
|
0.188
|
0.338
|
0.277
|
0.153
|
0.079
|
0.688
|
-0.087
|
0.659
|
R_middletemporal
|
-0.037
|
0.852
|
0.245
|
0.210
|
0.175
|
0.373
|
0.208
|
0.288
|
0.211
|
0.280
|
0.088
|
0.654
|
R_caudalmiddlefrontal
|
0.132
|
0.503
|
0.188
|
0.338
|
0.145
|
0.462
|
0.223
|
0.253
|
0.085
|
0.667
|
-0.053
|
0.788
|
R_lingual
|
-0.057
|
0.772
|
0.401
|
0.034
|
0.229
|
0.240
|
-0.114
|
0.562
|
0.231
|
0.236
|
0.169
|
0.390
|
R_supramarginal
|
0.065
|
0.741
|
0.080
|
0.686
|
0.142
|
0.471
|
0.306
|
0.113
|
0.179
|
0.361
|
0.091
|
0.644
|
R_superiortemporal
|
-0.096
|
0.629
|
0.101
|
0.610
|
0.097
|
0.624
|
0.160
|
0.415
|
0.307
|
0.112
|
0.275
|
0.157
|
L_paracentral
|
-0.058
|
0.77
|
0.344
|
0.073
|
0.389
|
0.041*
|
-0.007
|
0.973
|
0.309
|
0.109
|
0.180
|
0.358
|
L_posteriorcingulate
|
-0.043
|
0.828
|
0.018
|
0.928
|
0.047
|
0.812
|
0.055
|
0.780
|
0.352
|
0.066
|
0.208
|
0.288
|
L_precentral
|
-0.247
|
0.205
|
0.192
|
0.327
|
0.243
|
0.214
|
-0.087
|
0.661
|
0.185
|
0.347
|
0.067
|
0.736
|
*P value: <0.05