3. RESULTS
3.3 Classifying MCIc vs MCInc using single and joint modalities…
3.4.2 PLS…
We found 10 significant LVs (out of 23 LVs in total), which altogether explained 73% of the total covariance between task-based activity and RS connectivity. The significance of each LV can be found in Table 16 below.
Table 16. P-values corresponding to each LV after permutation testing.
LV p-value
LV1 0.00000
LV2 0.00300
LV3 0.00060
LV4 0.00300
LV5 0.00060
LV6 0.00040
LV7 0.00360
LV8 0.00300
LV9 0.01240
LV10 0.02180
LV11 0.05799
LV12 0.21636
LV13 0.71406
LV14 0.79044
LV15 0.98400
LV16 0.99600
LV17 0.99980
LV18 0.99980
LV19 0.99980
LV20 0.99980
LV21 0.99980
LV22 0.99980
LV23 0.99980
Below, we describe LV1 and LV2 as they distinguish our groups, and LV7, LV8 and LV9 as they are correlated to memory measures.
The first LV (Figure 22) is represented by a positive pattern of task activity in the right inferior frontal gyrus (IFG), right insula, left rolandic operculum, bilateral middle and superior occipital gyri, left angular gyrus, right supplementary motor area (SMA), bilateral hippocampi, and left
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middle temporal gyrus (MTG). There is also a negative pattern of activity in bilateral postcentral gyri, left precentral gyrus, left supramarginal gyrus, and cerebellum. Notably, many of these regions are part of DMN. On the RS connectome are involved several DMN regions such as anterior, middle and posterior cingulate cortex (ACC-MCC-PCC), left MTG and right superior temporal gyrus (STG). Some regions from the frontoparietal network, such as right middle/superior frontal gyrus, and bilateral insula, are also represented. Finally, other regions, such as left inferior frontal/orbitofrontal gyrus, bilateral angular gyri and bilateral supramarginal/inferior parietal gyri, are commonly associated with both networks. All connections were positive. Importantly, the sign of the patterns displayed cannot be interpreted as increased/decreased activity/connectivity, but only in relation to the opposite modality. Notably, both rest and task scores for LV1 were significantly different between MCI converters and nonconverters (t=-2.74, p=0.006 and z=2.34, p=0.019 respectively).
The second LV (Figure 23) implicated positive task activity in the bilateral insula and IFG, right middle frontal and orbitofrontal gyri, bilateral ACC and MCC, bilateral precuneus and superior parietal lobules. In addition, a pattern of negative activity was present in the left hippocampus, MTG, IFG, and bilateral cerebellum. These regions are commonly associated with the salience network and the DMN. On the rest connectome were involved left and right STG, right insula and ACC, left IFG and ACC, left MTG and left IFG, right supramarginal gyrus and MCC, and left middle occipital gyrus and right MTG. Again, this network is reminiscent of the salience and DMN networks. Moreover, both rest and task scores for LV2 were significantly different between EC and MCI patients (t=2.78, p=0.008 and z=2.34, p=0.020 respectively). Rest scores were also significantly different between MCI converters and nonconverters (t=-2.45, p=0.024).
The seventh LV (Figure 24) is characterized by a positive pattern of activity in the right MTG, right fusiform gyrus and parahippocampal gyrus, right insula and ACC, bilateral supedior medial frontal gyri and angular gyri. Moreover, a negative pattern of activity in the right hippocampus and parahippocampal gyrus, right MTG, left precuneus and cuneus, left IFG and insula, and left superior temporal pole. On the RS connectome, many DMN regions such as ACC-MCC-PCC, right SPG and IPG, right supramarginal and angular gyrus, left ITG and MTG. Task and rest scores were not different between groups.
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The eighth LV (Figure 25) is represented by positive activity in the left cerebellum, bilateral superior occipital gyri and cuneus, left angular and supramarginal gyri, ACC, and right insula.
There was also a pattern of negative activity in the right IFG and left middle frontal gyrus, and right middle occipital gyrus. On the rest connectome, the MCC and ACC, right IFG and left MFG, retrosplenial cortex, bilateral supramarginal gyri and middle occipital gyri were involved.
Task and rest scores did not differ between groups.
The ninth LV (Figure 26) involved positive activity in medial frontal and parietal regions, but also the left IFG and MTG, the right parahippocampal gyrus, the right rolandic operculum, and left cerebellum. A pattern of negative activity was also present in the right orbitofrontal gyrus, left MTG, bilateral calcarine gyri and right postcentral gyrus. On the rest connectome were involved the right thalamus, bilateral insula, left MTG, left cerebellum, right supramarginal and angular gyri, among others. Task and rest scores did not differ between groups.
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Figure 22. Representation of LV1 in the task activity space and the RS FC space.
R angular R STG R IFG R MFG
R insula
R calcarine
R RSC PCC
R thalamus MCC
L caudate
L MTG
L ITG
L angular L SPG
R supramarginal L IFG
L insula ACC
L supramarginal
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Figure 23. Representation of LV2 in the task activity space and the RS FC space.
L MFG
L mid occipital
R MTG
R angular
L STG R STG
R insula R SFG
L IFG ACC
L MTG
L PHG R supramarginal
R IFG
L precentral
R SPG
R mid occipital L cerebellum
R MCC
R MFG
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Figure 24. Representation of LV7 in the task activity space and the RS FC space.
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Figure 25. Representation of LV8 in the task activity space and the RS FC space.
R IFG
R mid/sup occipital R MFG
L mid/sup occipital
R angular R PHG
R hippocampus
L cerebellum L post insula
R caudate L thalamus
L hippocampus
L cerebellum L ITG
R MFG L MFG
L IFG
R MCC
L supramarginal
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Figure 26. Representation of LV9 in the task activity space and the RS FC space.
R MFG
R mid/sup occipital R SFG/MFG
L MFG/SFG L IFG
L ACC
L mid/sup occipital
R caudate
L ITG
L cerebellum
PCC
R supramarginal
R RSC
precuneus
R STG L post insula
L MTG
IPS
R precentral
R MTG
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Figure 27. Representation of LVs 3, 4, 5, 6, and 10 in both the task activity and RS FC space.
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3.4.3 Canonical correlation analysis
When testing for associations between LV scores and memory measures across all subjects, we found no significant correlations. However, we found significant associations within each group.
For CCA within EC, we found significant correlations between task/rest scores for LV7 and LV9, and memory (respectively r=0.85, p=0.048 and r=0.86, p=0.011). The weights associated with each LV/behavioral score are shown on Figure 28. For LV7, the correlation was driven by both task and rest scores (with opposite signs), and mostly by delayed recall performance. In contrast, for LV9, the correlation was much more driven by task scores, and by immediate recall, digit span backward and task accuracy for conditions with a new distractor.
In MCI, a significant correlation was found between task and rest scores for LV8 and memory performance (r=0.83, p=0.032). This correlation was driven by task scores exclusively, and delayed recall. Notably, an outlier can be seen on the scatterplot corresponding to LV8 on Figure 28. We tried removing it and re-computing the CCA, which resulted in a non significant correlation (r=0.75, p=0.229).
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Figure 28. Canonical correlations between LV scores and memory measures for the first component of LV7 (in EC), LV8 (in MCI) and LV9 (in EC). The scatterplots showing the correlations between behavioral and LV saliences is presented on the left, while the weights corresponding to each memory measure and each LV score are shown in the center and right, respectively.
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