Identifying Modulated Functional Connectivity in Corresponding Cerebral Networks in Facial Nerve Lesions Patients With Facial Asymmetry

Abstract

Facial asymmetry is the major complaint of patients with unilateral facial nerve lesions. Frustratingly, although patients experience the same etiology, the extent of oral commissure asymmetry is highly heterogeneous. Emerging evidence indicates that cerebral plasticity has a large impact on clinical severity by promoting or impeding the progressive adaption of brain function. However, the precise link between cerebral plasticity and oral asymmetry has not yet been identified. In the present study, we performed functional magnetic resonance imaging on patients with unilateral facial nerve transections to acquire in vivo neural activity. We then identified the regions of interest corresponding to oral movement control using a smiling motor paradigm. Next, we established three local networks: the ipsilesional (left) intrahemispheric, contralesional (right) intrahemispheric, and interhemispheric networks. The functional connectivity of each pair of nodes within each network was then calculated. After thresholding for sparsity, we analyzed the mean intensity of each network connection between patients and controls by averaging the functional connectivity. For the objective assessment of facial deflection, oral asymmetry was calculated using FACEgram software. There was decreased connectivity in the contralesional network but increased connectivity in the ipsilesional and interhemispheric networks in patients with facial nerve lesions. In addition, connectivity in the ipsilesional network was significantly correlated with the extent of oral asymmetry. Our results suggest that motor deafferentation of unilateral facial nerve leads to the upregulated ipsilesional hemispheric connections, and results in positive interhemispheric inhibition effects to the contralesional hemisphere. Our findings provide preliminary information about the possible cortical etiology of facial asymmetry, and deliver valuable clues regarding spatial information, which will likely be useful for the development of therapeutic interventions.

Keywords: cerebral plasticity; fMRI; facial asymmetry; facial nerve; functional connectivity; interhemispheric inhibition.

FIGURE 1

FACEgram was used to quantitatively assess the unaffected (A) or paralyzed (B) side of the oral commissure at rest. The bilateral pupil and midpoint were used to establish a coordinate system. The oa-score”coreinate system. Thfrom the oral commissure perpendicular to the horizontal line at the bottom edge of the lower lip (blue line). The “b-score”corefrom the oral commissure perpendicular to the vertical line (red line). The “ac-score”corefrom the oral commissure to the bottom edge of the lower lip (green line). The photo shows the static outcome of a 31-year-old woman at 1 year postoperative. The difference in bilateral oral commissure (c_dif = 5.48) was determined by the unaffected (c_ua = 27.28) minus the paralyzed (c_p = 21.79) oral commissure positions (c_dif = c_ua - c_p).

FIGURE 2

Random effects group analysis of the facial smiling task. Activations (one sample t-test, p < 0.05, FDR corrected) in response to blocked (15 s) movement of the bilateral mouth angle are shown superimposed on a template cortex. Images from the control group (n = 15) are shown in the upper part of the figure, while images from the patients (n = 22) are shown in the lower part. PoCG, postcentral gyrus; PreCG, precentral gyrus; SMA, supplementary motor area; MFG, middle frontal gyrus; MTG, middle temporal gyrus; R, right; L, left; FP, facial paralysis patients; HC, healthy controls. Color bar shows the t-value.

FIGURE 3

Significant differences between patients and controls in the motor task. Hot colors represent areas that were significantly greater in the controls (n = 15) compared with patients (n = 22), while cold colors represent areas that were significantly greater in the patients compared with controls (two sample t-test, p < 0.05, FDR corrected). The histograms show significant clusters in the right and left hemispheres, respectively. PoCG, postcentral gyrus; PreCG, precentral gyrus; SMA, supplementary motor area; MFG, middle frontal gyrus; MTG, middle temporal gyrus; INS, insula; R, right; L, left. Color bar shows the t-value.

FIGURE 4

Cerebral networks for the estimation of functional connectivity. The identified areas constitute the right hemispheric, left hemispheric, and interhemispheric networks. The nodes represent the peak activated locations, and the edges represent the strengths of connectivity. The images from controls are shown in the upper part of the figure, while images from the patients are shown in the lower part. Sparsity was set to 50%. PoCG, postcentral gyrus; PreCG, precentral gyrus; SMA, supplementary motor area; MFG, middle frontal gyrus; MTG, middle temporal gyrus; INS, insula; R, right; L, left; FP, facial paralysis patients; HC, healthy controls.

FIGURE 5

Statistical analysis of the mean functional connectivity of cerebral networks between the two groups. The mean functional connectivity in the left, right, and inter-hemispheric networks of patients (n = 22) and controls (n = 15) are shown. These network-specific averaged z-score values (via Fisher’s z-transformation) were then tested for differences both within and between groups. *p < 0.05 between groups; ^#p < 0.05 within groups; paired t-test.

FIGURE 6

Correlations between connectivity and clinical data in the patient group (n = 22). The Pearson correlations of the average connectivity and age of individual patients with oral asymmetry are shown. (A) There was a significant correlation between functional connectivity in the ipsilesional network (left hemisphere, R² = 0.25, p < 0.05) and c_dif; increased connectivity correlated with greater oral asymmetry. (B–D) Contralesional hemispheric connectivity (right hemisphere, R² = 0.12, p > 0.05), interhemispheric connectivity (R² = 0.13, p > 0.05), and age (R² = 0.12, p > 0.05) were not significantly correlated with c_dif.