Background and Purpose

The patients with asymptomatic internal carotid stenosis (aICS) have a higher risk of ischemic stroke.[1] In addition to vascular events, previous studies have pointed out that the patients with aICS may also suffer from dizziness and cognitive impairment (verbal memory), which were possibly attributed to the impaired perfusion.[2] However, the comparison of functional connectivity (FC) and corresponding symptoms between left and right aICS was less explored. In this study, we aimed to investigate whether the laterality of aICS is a factor associated with the organization of FC and the type/extent of presented neurocognitive symptoms. We hypothesized that the association between the FC and neuropsychological measures would be different between left and right aICS groups.

Materials and Methods

We recruited 36 healthy controls (HCs), 26 patients with left aICS (aICS_L), and 40 patients with right aICS (aICS_R). Inclusion criteria of patients were the degree of stenosis greater than 60%, and no neurodegenerative diseases. Dizziness handicap inventory (DHI) and verbal memory test were used to evaluate the severity of dizziness and level of working (immediate) and short-term (delayed recall) memory, respectively (Table 1).[3] MRI data, including 3D BRAVO T1-weighted images (TR/TE: 12.2/5.2 ms; voxel size: 1.0×1.0×1.0 mm3) and EPI BOLD fMRI (TR/TE: 3000/30ms; voxel size: 1.73×1.73×3mm3) during resting state (124 volumes) were acquired on a 3T MR scanner (GE, Discovery 750).
The fMRI data were preprocessed with the standard procedures using Data Processing Assistant for Resting-State fMRI (DPARSF) toolbox.[4] The preprocessing procedures included the correction for slice timing, realignment, co-registration of 3D-T1W images to BOLD fMRI, regression out confounding effects of motion parameters and signals from white matter and cerebrospinal fluid, spatial normalization, and spatial smoothing with a 6-mm full-width half-maximum Gaussian kernel. The cortical and subcortical regions were parcellated into 116 regions based on the Automatic Anatomical Labeling atlas (AAL116).[5] The FC was estimated by calculating Pearson’s correlation coefficient between each pair of regional BOLD signals (with a bandpass filtering between 0.01 and 0.10 Hz) followed by the Fisher’s r-to-z transform.
Two-sample t-test was used to identify the significant differences of FC between aICS_L and aICS_R groups (p<0.05). Correlation analysis was performed to further reveal the associations between FC and neuropsychological measures (p < 0.05). The processing workflow is shown in Figure 1.

Results and Discussion

The patients with aICS had significantly more severe dizziness and deficit on verbal memory test compared to the HCs (Table 1). For the comparison between aICS_L and aICS_R groups, the recall verbal memory was significantly poorer in the aICS_L than in the aICS_R group (Table 1).
Figure 2 shows the significant differences of FC matrices between aICS_L and aICS_R groups. In the aICS_R group, several significantly stronger FC (positive t values labelled by yellow in Figure 2) were found within motor areas, between motor and visual areas, and cerebellum areas compared to the aICS_L group. Few significant lower values of FCs (negative t values labelled by blue in Figure 2) were observed within visual areas and between visual and cerebellum areas in the aICS_R group. Results showed that patients with aICS_L tended to have reduced FC in most of significantly different connectivity compared to the aICS_R group.
To further investigate the association between the altered FC and neuropsychological assessments (DHI, immediate verbal memory, and recall verbal memory), we displayed scatter plots with significant correlations for the aICS_L and aICS_R group, respectively (Figure 3). In general, the aICS_L group exhibited stronger correlations (higher absolute correlation coefficients) between FC and neuropsychological assessments compared to the aICS_R group. For example, the FC between the right calcarine and vermis12 showed a positive correlation (R=0.515) with dizziness score, indicating that a stronger FC may accompany a higher degree of dizziness. Calcarine is involved in the visual function, and the function of vermis is related to posture control. Accordingly, the alteration of FC between the right calcarine and vermis12 may be associated with vertigo after aICS_L.[6] The FC between the left fusiform and right inferior temporal gyrus also showed negative correlations with immediate verbal memory (R=-0.656) and recall verbal memory (R=-0.569) in the aICS_L group. Fusiform is directly related to textual cognition. Inferior temporal handles the object identification by comparing the processed information to stored memories of objects. With the trigger of stored memory, the FC between the right fusiform and left inferior temporal may compensate the cognitive impairment (working and short-term memory) in aICS_L.

Conclusions

In this study, we reported that patients with aICS_L showed poorer performance in the recall verbal memory and significant decreased FC analysis compared to patients with aICS_R. Different profiles of association between FC and neuropsychological assessments were found between two aICS groups. Based on our results, the laterality of aICS can be one of the key factors to link with the decline of verbal memory function and guide the treatment for patients with aICS.

Acknowledgements

This work was supported by the Ministry of Science and Technology, Taiwan (MOST 109-2314-B-010-022-MY3) and the National Yang-Ming University (VGHUST110-G7-2-2).