Affective Circuitry Alterations in Patients with Trigeminal Neuralgia

Abstract

Trigeminal neuralgia (TN) is a severe chronic neuropathic facial pain disorder. Affect-related behavioral and structural brain changes have been noted across chronic pain disorders, but have not been well-studied in TN. We examined the potential impact of TN (37 patients: 23 with right-sided TN, 14 with left-sided TN), compared to age- and sex-matched healthy controls, on three major white matter tracts responsible for carrying affect-related signals-i.e., cingulum, fornix, and medial forebrain bundle. Diffusion magnetic resonance imaging (dMRI), deterministic multi-tensor tractography for tract modeling, and a model-driven region-of-interest approach was used. We also used volumetric gray matter analysis on key targets of these pathways (i.e., hippocampus, cingulate cortex subregions, nucleus accumbens, and ventral diencephalon). Hypotheses included: (1) successful modeling of tracts; (2) altered white matter microstructure of the cingulum and medial forebrain bundle (via changes in dMRI metrics such as fractional anisotropy, and mean, axial, and radial diffusivities) compared to controls; (3) no alterations in the control region of the fornix; (4) corresponding decreases in gray matter volumes. Results showed (1) all 325 tracts were successfully modeled, although 11 were partially complete; (2) The cingulum and medial forebrain bundle (MFB) were altered in those with TN, with dMRI metric changes in the middle (p = 0.001) and posterior cingulum (p < 0.0001), and the MFB near the ventral tegmental area (MFB-VTA) (p = 0.001). The posterior cingulum and MFB-VTA also showed unilateral differences between right- and left-sided TN patients; (3) No differences were noted at any fornix subdivision; (4) decreased volumes were noted for the hippocampus, posterior cingulate, nucleus accumbens, and ventral diencephalon. Together, these results support the notion of selectively altered affective circuits in patients with TN, which may be related to the experience of negative affect and the increased comorbidity of mood and anxiety disorders in this population.

Keywords: DTI; MRI; chronic neuropathic pain; dMRI; diffusion magnetic resonance; emotion; gray matter; structural neuroimaging.

Figure 1

Tracts and ROIs. Example of fornix, cingulum, and MFB multi-tensor tractography models in a single subject with regions-of-interest (ROIs) indicated by black lines. NAc, nucleus accumbens/ventral striatum; PFC, prefrontal cortex; VTA, ventral tegmental area.

Figure 2

Illustration of statistical design. CN, control subjects; ROI, region of interest; R- and L-TN, trigeminal neuralgia patients with right- and left-sided pain, respectively.

Figure 3

Main dMRI findings in cingula (FA) and MFB-VTA (MD). Scatterplots showing ROIs where fractional anisotropy (FA) for the middle and posterior cingula, and mean diffusivity (MD) for the MFB-VTA, is different from controls (^*) or between patient groups (θ), indicated by post-hoc tests (p < 0.05) following repeated measures ANOVA. MD was scaled up by 1000x. Corresponding changes in other dMRI metrics for these regions are indicated in Table 3.

Figure 4

Main GM findings. The main results showing gray matter (GM) decreases in patients with TN compared to healthy controls (CN). ^* = significant between groups; # L NAc is smaller than R NAc in CN; all results are significant at p < 0.05 following ANOVA with corrections for multiple comparisons. Hipp, (Hippocampus); NAc, (nucleus accumbens); PCC, (posterior cingulate cortex); VD, (ventral diencephalon). See Table 4 for corresponding statistics.