Structural and Functional Brain Changes in Patients With Classic Trigeminal Neuralgia: A Combination of Voxel-Based Morphometry and Resting-State Functional MRI Study

Abstract

Objectives: Brain structural and functional abnormalities have been separately reported in patients with classic trigeminal neuralgia (CTN). However, whether and how the functional deficits are related to the structural alterations remains unclear. This study aims to investigate the anatomical and functional deficits in patients with CTN and explore their association.

Methods: A total of 34 patients with CTN and 29 healthy controls (HCs) with age- and gender-matched were recruited. All subjects underwent structural and resting-state functional magnetic resonance imaging (fMRI) scanning and neuropsychological assessments. Voxel-based morphometry (VBM) was applied to characterize the alterations of gray matter volume (GMV). The amplitude of low-frequency fluctuation (ALFF) method was used to evaluate regional intrinsic spontaneous neural activity. Further correlation analyses were performed between the structural and functional changes and neuropsychological assessments.

Results: Compared to the HCs, significantly reduced GMV was revealed in the right hippocampus, right fusiform gyrus (FFG), and temporal-parietal regions (the left superior/middle temporal gyrus, left operculo-insular gyrus, left inferior parietal lobule, and right inferior temporal gyrus) in patients with CTN. Increased functional activity measured by zALFF was observed mainly in the limbic system (the bilateral hippocampus and bilateral parahippocampal gyrus), bilateral FFG, basal ganglia system (the bilateral putamen, bilateral caudate, and right pallidum), left thalamus, left cerebellum, midbrain, and pons. Moreover, the right hippocampus and FFG were the overlapped regions with both functional and anatomical deficits. Furthermore, GMV in the right hippocampus was negatively correlated with pain intensity, anxiety, and depression. GMV in the right FFG was negatively correlated with illness duration. The zALFF value in the right FFG was positively correlated with anxiety.

Conclusion: Our results revealed concurrent structural and functional changes in patients with CTN, indicating that the CTN is a brain disorder with structural and functional abnormalities. Moreover, the overlapping structural and functional changes in the right hippocampus and FFG suggested that anatomical and functional changes might alter dependently in patients with CTN. These findings highlight the vital role of hippocampus and FFG in the pathophysiology of CTN.

Keywords: amplitude of low-frequency fluctuations; classic trigeminal neuralgia; neuropathic pain; resting-state functional MRI; voxel-based morphometry.

FIGURE 1

GMV alterations in patients with CTN. Differences between the patients with CTN and HCs were analyzed using a two-sample t-test. The statistical significance level was set at p < 0.05, FDR corrected. Patients with CTN showed significantly increased GMV in the right hippocampus, right FFG, right ITG, left STG, left operculo-insular gyrus, and left MTG. The color bar displayed t-values. GMV, gray matter volume; CTN, classic trigeminal neuralgia; HC, healthy control; FFG, fusiform gyrus; ITG, inferior temporal gyrus; STG, superior temporal gyrus; MTG, middle temporal gyrus.

FIGURE 2

zALFF alterations in patients with CTN. The differences between the CTN patients and HCs were analyzed using a two-sample t-test. The statistical significance level was set at p < 0.05, FDR corrected. Patients with CTN showed significantly decreased zALFF in the bilateral hippocampus, bilateral fusiform FFG, bilateral caudate, left thalamus, bilateral putamen, right pallidum, bilateral PHG, and left cerebellum. The color bar displayed t-values. ALFF, amplitude of low-frequency fluctuation; CTN, classic trigeminal neuralgia; HC, healthy control; FFG, fusiform gyrus; PHG, parahippocampal gyrus.

FIGURE 3

Overlapped brain region with structural and functional changes. The right hippocampus (first row) and right fusiform gyrus (second row) within the red circle represent the overlapped areas with both increased zALFF (hot colored regions) and decreased GMV (cold colored regions) in patients with CTN. GMV, gray matter volume; ALFF, amplitude of low-frequency fluctuation; CTN, classic trigeminal neuralgia.

FIGURE 4

Correlation between GMV, zALFF alterations, and clinical variables in patients with CTN. GMV in the right hippocampus was negatively associated with VAS (A), HAMA (B), and HAMD (C) scores of patients with CTN. GMV in the right FFG was negatively correlated with illness duration (D). Increased zALFF in the right FFG was positively correlated with HAMA score of the patients with CTN (E). GMV, gray matter volume; ALFF, amplitude of low-frequency fluctuation; CTN, classic trigeminal neuralgia; HIP, hippocampus; VAS, visual analog scale; HAMA, Hamilton Anxiety Rating Scale; HAMD, Hamilton Depression Rating Scale; FFG, fusiform gyrus.