When pain becomes self: limbic-default mode network hyperconnectivity predicts microvascular decompression failure in...

Microvascular decompression is the standard surgical intervention for classical trigeminal neuralgia attributed to NVC. However, up to 30% of patients experience poor outcomes despite technically successful surgery, suggesting non-peripheral mechanisms. This study investigates whether central neural reorganization-manifested as altered cortico-subcortical connectivity and white matter microstructure-underlies poor surgical outcomes in patients with 'incidental' low-pressure vascular contact. In this prospective nested case-control study, we enrolled 60 patients with medication-refractory classical trigeminal neuralgia who underwent microvascular decompression and 30 matched healthy controls. Based on the 3-month surgical outcome, patients were retrospectively stratified into effective and ineffective groups. All participants underwent preoperative resting-state functional MRI and diffusion tensor imaging. Whole-brain functional connectivity between 100 cortical (Schaefer atlas) and 16 subcortical (Tian atlas) regions was analysed. Connections were ranked by between-group effect size (Cohen's d); the top 10 were used to train a SVM classifier. Correlational tractography assessed the relationship between fractional anisotropy and disease duration. Despite comparable preoperative pain, the ineffective group had significantly lower intraoperative vascular pressure (P = 0.02). Compared to the effective group, the ineffective group exhibited significantly enhanced functional connectivity between default mode, somatomotor and control networks and subcortical limbic structures (amygdala, nucleus accumbens, hippocampus) (P < 0.05, permutation test). A SVM classifier trained on these features achieved 86.0% accuracy (AUC = 0.931) in distinguishing outcome groups. Diffusion tensor imaging analysis revealed that longer disease duration was associated with decreased fractional anisotropy in sensorimotor white matter tracts, indicating progressive microstructural decline. Poor surgical outcome is not merely ineffective decompression, but a signature of maladaptive central reorganization-specifically, heightened default mode network-limbic coupling. This hyperconnectivity indicates that pain has become cognitively and affectively 'self-embedded', transitioning from a sensory event to a persistent self-referential narrative that sustains pain even after peripheral trigger removal. These results reframe a subset of trigeminal neuralgia as a central network disorder of pain self-representation and identify default mode network-amygdala hyperconnectivity as a candidate target for circuit-based neuromodulation-such as repetitive transcranial magnetic stimulation over medial prefrontal hubs-to 'unlearn' the embedded pain trace, either adjunctively or as an alternative to microvascular decompression.