Structural-functional network decoupling in early ALS tied to microglial gene FMN1

In early-stage ALS, structural–functional coupling is significantly reduced in the somatomotor network (pFDR=0.001), while structural connectivity appears preserved. The decoupling correlates spatially with 5-HT2A/mGluR5 receptors and a microglial gene signature, notably FMN1 do…

• Prospective cohort: 73 sporadic early-stage ALS patients vs. 74 matched healthy controls, using DTI and resting-state fMRI.
• A gradient boosting machine classified patients with primary contribution from left precentral gyrus SC-FC coupling (exact AUC not reported in source).
• Key limitation: single-site study without external validation of the imaging-transcriptomic associations and machine learning model.

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