General characteristics
Detailed demographic and clinical data for the cTLE-N, rTLE-N, and HC groups are shown in Table 1. The three groups were well matched for age and gender, with no statistically significant differences (P>0.05). Likewise, the lateralization of TLE did not differ between the cTLE-N and rTLE-N group. RTLE-N patients had a lower age of onset than cTLE-N (Z= -2.158, P=0.031). RTLE-N patients had a longer disease duration than cTLE-N (Z= -2.211, P=0.027). In neurocognitive tests, rTLE-N patients had lower MoCA score than cTLE-N patients (t=2.787, P=0.009).
Table 1
Clinical Data of the TLE-N Patients and HC
characteristics
|
HC(n=30)
|
cTLE-N(n=30)
|
rTLE-N(n=21)
|
P
|
Age (y)
|
38.03±8.68
|
34.17±9.36
|
32.62±9.21
|
0.088*
|
Gender (male/female)
|
12/18
|
14/16
|
13/8
|
0.299#
|
Lateralization (L/R)
|
-
|
18/12
|
15/6
|
0.553#
|
Age of onset (y)
|
-
|
34(17.25,37)
|
18(14,20)
|
0.031+
|
Epilepsy durations (y)
|
-
|
5.5(1,20)
|
13(6.5,18.5)
|
0.027+
|
MoCA Score
|
-
|
25.73±2.57
|
23.10±3.77
|
0.009~
|
Data conforming to a normal distribution are expressed as mean, and non-normal distribution is expressed as M(Q1, Q3). |
* The P-value was obtained by analysis of variance. |
# The P-value was obtained by a 2-tailed Pearson Chi-square test. |
+ The P-value was obtained by Wilcoxon rank sum text. |
~ The P-value was obtained by 2-sample 2-tailedttest. |
Significant statistical results are shown in bold. |
Alterations of gray matter volume
A one-way ANOVA was performed to obtain the difference in GMV among the three groups (P< 0.001). Supplementary Figure 1 illustrates the cerebral regions with significant differences among groups, which included the the bilateral hippocampus, middle temporal gyrus and precuneus, right temporal pole (middle temporal gyrus), insula, orbital superior frontal gyrus, orbital middle frontal gyrus, frontal middle gyrus, triangular inferior frontal gyrus, medial and paracingulate gyrus, superior parietal gyrus, supplementary motor area and cerebellum, left middle occipital gyrus, thalamus, amygdala, central precentral gyrus, and postcentral gyrus (Supplementary Table 1).
Post-hoc t-tests were conducted between the three groups to compare the GMV of these regions (Table 2). Compared with the HC group, the cTLE-N group showed reduced GMV in the bilateral thalamus and right lingual gyrus; increased GMV in the right cerebellum, inferior temporal gyrus, hippocampus, parahippocampal gyrus, amygdala, fusiform gyrus and orbital middle frontal gyrus, and left postcentral gyrus region (Figure 1). The rTLE-N group showed decreased GMV in the left hippocampus, fusiform gyrus, and thalamus; increased GMV in the bilateral cerebellum and temporal pole (middle temporal gyrus), right fusiform gyrus, amygdala, and hippocampus, and left middle occipital gyrus regions (Figure 2). The rTLE-N group exhibited reduced GMV in the left hippocampus, right insula, and right precuneus and increased GMV in the left middle occipital gyrus compared with the cTLE-N group (Supplementary Figure 2).
Table 2
Distribution of brain areas with differences in GMV between the two groups (P<0.05, FDR corrected)
Brain Region(AAL)
|
Hemisphere
|
Cluster Size
|
MNI(mm)
|
t
|
|
x
|
y
|
z
|
HC>cTLE-N
|
|
|
|
|
|
|
Lingual
|
R
|
156
|
15
|
-85.5
|
-13.5
|
4.03
|
Thalamus
|
L
|
845
|
-19.5
|
-25.5
|
4.5
|
4.72
|
Thalamus
|
R
|
165
|
16.5
|
-22.5
|
0
|
5.32
|
HC
|
|
|
|
|
|
|
Cerebelum_Crus1
|
R
|
102
|
42
|
-72
|
-22.5
|
-6.17
|
Temporal_Inf
|
R
|
165
|
54
|
-15
|
-34.5
|
-5.95
|
Hippocampus
|
R
|
810
|
27
|
-4.5
|
-25.5
|
-6.88
|
ParaHippocampal
|
R
|
Amygdala
|
R
|
Fusiform
|
R
|
163
|
48
|
-37.5
|
-28.5
|
-6.26
|
Frontal_Med_Orb
|
R
|
257
|
9
|
57
|
-13.5
|
-6.32
|
Postcentral
|
L
|
227
|
-21
|
-40.5
|
66
|
-6.34
|
HC>rTLE-N
|
|
|
|
|
|
|
Hippocampus
|
L
|
328
|
-36
|
-28.5
|
-13.5
|
4.41
|
Fusiform
|
L
|
164
|
-19.5
|
-87
|
-9
|
4.51
|
Thalamus
|
L
|
537
|
0
|
-9
|
13.5
|
4.83
|
HC
|
|
|
|
|
|
|
Cerebelum_8
|
L
|
128
|
-21
|
-42
|
-49.5
|
-5.93
|
Cerebelum_6
|
R
|
582
|
36
|
-69
|
-21
|
-5.38
|
Fusiform
|
R
|
229
|
36
|
-13.5
|
-34.5
|
-4.77
|
Temporal_Pole_Mid
|
L
|
231
|
-52.5
|
12
|
-33
|
-5.52
|
Temporal_Pole_Mid
|
R
|
179
|
49.5
|
21
|
-27
|
-5.02
|
Amygdala
|
R
|
483
|
27
|
-4.5
|
-13.5
|
-4.93
|
Hippocampus
|
R
|
103
|
Occipital_Mid
|
L
|
334
|
-30
|
-91.5
|
7.5
|
-5.28
|
cTLE-N>rTLE-N
|
|
|
|
|
|
|
Hippocampus
|
L
|
160
|
-36
|
-22.5
|
-18
|
5.71
|
Insula
|
R
|
154
|
42
|
16.5
|
-7.5
|
5.67
|
Precuneus
|
R
|
232
|
10.5
|
-69
|
33
|
5.57
|
cTLE-N
|
|
|
|
|
|
|
Occipital_Mid
|
L
|
105
|
-28.5
|
-94.5
|
7.5
|
-4.80
|
Alterations of Cortical thickness
A one-way ANOVA was performed to obtain the difference in CT among the three groups (P< 0.001). Supplementary Figure 1 illustrates the cerebral regions with significant differences among groups, which included the bilateral parahippocampal gyrus, superior frontal gyrus and precentral gyrus, the left supramarginal gyrus, inferior parietal gyrus, superior temporal gyrus, lateral occipital lobe, inferior middle frontal gyrus, medial orbitofrontal and lateral orbitofrontal, and the right paracentral lobule, superior anterior cingulate gyrus, precuneus, temporal pole, superior parietal gyrus and fusiform gyrus (Supplementary Table 2).
Post-hoc t-tests were conducted between the three groups to compare the CT of these regions. The cTLE-N group exhibited a thinner CT of the left medial orbitofrontal and lateral occipital cortex (Figure 1, Table 3). The rTLE-N group showed thinning of CT in the left medial orbitofrontal, temporal pole, middle temporal gyrus and the upper right anterior cingulate gyrus (Figure 2, Table 4). No brain areas with increased CT were noted in either TLE-N group compared to the control group. The rTLE-N group compared to cTLE-N group showed thinning of CT in the upper anterior cingulate gyrus, precentral gyrus and middle temporal gyrus bilaterally, left superior marginal gyrus, lower middle frontal gyrus, superior temporal gyrus and inferior frontal gyrus orbitally, right postcentral gyrus, paracentral lobule, posterior superior temporal gyrus, superior parietal gyrus, parietal gyrus, inferior parietal gyrus, superior frontal gyrus and precuneus, inferior gyrus, superior frontal gyrus, superior middle frontal gyrus, and precuneus. (Supplementary Figure 2, Table 5).
Table 3
Brain regions with thinner CT in the cTLE-N group compared with controls (Desikan-Killiany DK40 Atlas)
Left Hemisphere
|
HC(Mean(SD))
|
cTLE-N(Mean(SD))
|
MNI
|
t
|
x
|
y
|
z
|
medialorbitofrontal
|
2.75(0.30)
|
2.57(0.27)
|
-7
|
52
|
-13
|
4.46
|
lateraloccipital
|
2.53(0.33)
|
2.28(0.14)
|
-40
|
-35
|
-27
|
3.63
|
Table 4
Brain regions with thinner CT in the rTLE-N group compared with controls (Desikan-Killiany DK40 Atlas)
Left Hemisphere
|
HC(Mean(SD))
|
rTLE-N(Mean(SD))
|
MNI
|
t
|
x
|
y
|
z
|
medialorbitofrontal
|
2.82(0.23)
|
2.56(0.26)
|
0
|
51
|
-16
|
5.36
|
temporalpole
|
3.73(0.27)
|
3.43(0.25)
|
-28
|
62
|
-31
|
3.78
|
middletemporal
|
3.24(0.28)
|
3.01(0.33)
|
-54
|
-15
|
-24
|
3.56
|
Right Hemisphere
|
|
|
|
|
|
|
caudalanteriorcingulate
|
2.78(0.35)
|
2.63(0.33)
|
11
|
62
|
16
|
3.77
|
Table 5
Brain regions with thinner CT in the rTLE-N group compared with cTLE-N (Desikan-Killiany DK40 Atlas)
|
cTLE-N(Mean(SD))
|
rTLE-N(Mean(SD))
|
MNI
|
|
t
|
Left Hemisphere
|
x
|
y
|
z
|
supramarginal
|
2.96(0.23)
|
2.74(0.17)
|
-56
|
-57
|
14
|
4.20
|
rostralanteriorcingulate
|
2.84(0.18)
|
2.61(0.21)
|
-1
|
23
|
-4
|
4.92
|
rostralmiddlefrontal
|
2.80(0.18)
|
2.66(0.13)
|
-39
|
26
|
30
|
4.20
|
precentral
|
2.77(0.32)
|
2.49(0.33)
|
-31
|
-44
|
55
|
3.82
|
superiortemporal
|
3.04(0.22)
|
2.82(0.25)
|
-61
|
-35
|
-2
|
4.16
|
parsorbitalis
|
3.01( 0.23)
|
2.84(0.19)
|
-47
|
17
|
6
|
3.62
|
middletemporal
|
3.57(0.29)
|
3.40(0.29)
|
-57
|
8
|
-9
|
3.56
|
Right Hemisphere
|
|
|
|
|
|
|
caudalanteriorcingulate
|
2.72(0.20)
|
2.46(0.26)
|
7
|
23
|
23
|
5.03
|
postcentral
|
2.45(0.14)
|
2.26(0.20)
|
38
|
-42
|
35
|
5.27
|
paracentral
|
2.89(0.20)
|
2.67(0.23)
|
9
|
-36
|
34
|
5.68
|
bankssts
|
2.94(0.14)
|
2.78(0.21)
|
51
|
-47
|
-8
|
4.32
|
precentral
|
3.00(0.20)
|
2.82(0.22)
|
62
|
-3
|
16
|
4.24
|
superiorparietal
|
2.35(0.18)
|
2.19(0.16)
|
14
|
-88
|
4
|
5.63
|
inferiorparietal
|
2.75(0.17)
|
2.56(0.18)
|
54
|
-54
|
1
|
4.67
|
superiorfrontal
|
3.31(0.23)
|
3.10(0.24)
|
7
|
7
|
44
|
4.10
|
caudalmiddlefrontal
|
2.88(0.22)
|
2.75(0.14)
|
52
|
3
|
35
|
4.09
|
precuneus
|
2.93(0.22)
|
2.78(0.17)
|
3
|
-58
|
3
|
4.06
|
middletemporal
|
3.16(0.23)
|
2.93(0.24)
|
58
|
-35
|
-14
|
3.95
|
Correlation analysis
In cTLE-N group, GMV of left thalamus (rs =-0.399, P=0.029), right thalamus (rs =-0.404, P=0.027), right fusiform gyrus (rs =-0.580, P=0.001), right orbital middle frontal gyrus (rs=-0.643, P=0.001) were negatively correlated with onset age. The right hippocampal GMV was negatively correlated with the disease duration (rs =-0.454, P=0.012), and the right hippocampal GMV was positively correlated with MoCA score (rp =0.425, P=0.019) (Supplementary Table 3). In the rTLE-N group, GMV of the left hippocampus (rp=0.603, P=0.004), left fusiform gyrus (rp=0.634, P=0.002), left thalamus (rp=0.489, P=0.024), left temporal pole middle temporal gyrus (rs=0.524, P=0.015), and left occipital middle gyrus (rp=0.655, P=0.001) were correlated with MoCA score was positively correlated. Left thalamus GMV was negatively related to disease duration (rs=-0.540, P=0.011) (Supplementary Table 4).
In the cTLE-N group, CT of the left lateral occipital lobe (rs=-0.477, P=0.008) and left medial orbitofrontal (rs=-0.425, P=0.019) was negatively correlated with age at onset. The CT of the left lateral occipital lobe (rs=-0.400, P=0.029) and left medial orbitofrontal cortex (rs=-0.451, P=0.012) was negatively correlated with disease duration. The CT of left medial orbitofrontal (rp=0.466, P=0.009) was positively correlated with MoCA score (Supplementary Table 5). In the rTLE-N group, left medial orbitofrontal (rs=-0.598, P=0.004) and left middle temporal gyrus (rs=-0.560, P=0.008) CT was negatively correlated with disease duration. The left medial orbitofrontal (rs=0.411, P=0.024), left temporal pole (rp=0.503, P=0.020) and left middle temporal gyrus (rp=0.602, P=0.004) were positively correlated with MoCA score (Supplementary Table 5).