Neurofunctional divergence between classical and idiopathic trigeminal neuralgia: A large-cohort resting-state fMRI study of 139 patients

Aug 31, 2025Clinical neurology and neurosurgery

Differences in brain activity between typical and unexplained trigeminal nerve pain from resting brain scans of 139 patients

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Abstract

Patients with idiopathic trigeminal neuralgia (ITN) may show different brain activity patterns compared to those with classical trigeminal neuralgia (CTN).

Trigeminal neuralgia patients had lower regional homogeneity (ReHo) in the right fusiform gyrus and higher ReHo in the right thalamus compared to healthy controls.
ITN patients exhibited higher amplitude of low-frequency fluctuations (ALFF) in the right hippocampus and lower fractional ALFF in the bilateral postcentral gyrus than CTN patients.
ReHo in the right fusiform gyrus was negatively correlated with pain intensity, while ReHo in the right thalamus had a positive correlation.
In the CTN group, connectivity between the left supramarginal gyrus and right perigenual cingulate gyrus was inversely related to disease duration.
These neurofunctional changes may help identify biomarkers for distinguishing TN subtypes and could inform treatment approaches.

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BACKGROUND: Resting-state functional MRI (rs-fMRI) has advanced our understanding of trigeminal neuralgia (TN), but the neural distinctions between its classical (CTN) and idiopathic (ITN) subtypes are poorly understood. This study aims to investigate differential brain activity and connectivity patterns between CTN and ITN to elucidate their underlying central mechanisms and identify potential neuroimaging biomarkers.

METHODS: This prospective study included rs-fMRI data from 139 TN patients (84 CTN, 55 ITN) and 49 matched healthy controls (HCs). We analyzed the amplitude of low-frequency fluctuations (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo), and functional connectivity (FC). Group comparisons were performed using two-sample t-tests with cluster-level family-wise error (FWE) correction. Correlations between imaging metrics and clinical variables were assessed.

RESULTS: Compared to HCs, TN patients exhibited decreased ReHo in the right fusiform gyrus and increased ReHo in the right thalamus. Subtype analysis revealed that ITN patients, compared to CTN, showed significantly increased ALFF in the right hippocampus and decreased fALFF in the bilateral postcentral gyrus. Clinically, ReHo in the right fusiform gyrus negatively correlated with pain intensity (VAS; r = -0.255, p = 0.002), while right thalamic ReHo showed a positive correlation (r = 0.208, p = 0.014). In the CTN subgroup, connectivity between the left supramarginal gyrus and right perigenual cingulate gyrus was inversely correlated with disease duration (r = -0.267, p = 0.014).

CONCLUSION: Our findings reveal divergent rs-fMRI profiles for TN patients versus HCs, and notably, between CTN and ITN subtypes. These distinctions, particularly the hippocampal hyperactivity in ITN, suggest different central pathophysiological mechanisms. These quantifiable neurofunctional alterations may serve as potential biomarkers to differentiate TN subtypes and guide personalized therapeutic strategies.

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