Aberrant hypothalamic-cortical functional connectivity in spinal cord injury: a neuroimaging-transcriptomic study for motor recovery prognostication.

OBJECTIVE: Spinal cord injury (SCI) disrupts supraspinal projections to spinal motor circuits, resulting in sensorimotor deficits. While emerging evidence implicates hypothalamic engagement in post-SCI locomotor recovery, the integrity of hypothalamic-cortical functional connectivity (FC) and its prognostic utility remain uncharacterized. METHODS: Here, the authors employed voxelwise resting-state functional MRI (fMRI) and multivariate pattern analysis to map hypothalamic-cortical FC alterations in 30 incomplete SCI patients relative to 30 demographically matched healthy controls (HCs). Longitudinal assessments at 6-month follow-up integrated clinical metrics (American Spinal Injury Association [ASIA] motor/sensory scores) and transcriptomic decoding via spatial correlation with Allen Human Brain Atlas gene expression profiles. RESULTS: Mass univariate comparisons revealed reduced FC between the hypothalamus and key motor regions, supplementary motor area (SMA), precentral gyrus, and cerebellar crus in SCI patients versus HCs (cluster-level family-wise error-corrected p < 0.05). Baseline hypothalamic-SMA FC strength positively predicted initial motor impairment (Pearson's r = 0.76, p < 0.001). Longitudinal analysis demonstrated FC reorganization paralleling motor recovery (ΔFC vs ΔASIA motor score, r = 0.36, p = 0.04), and searchlight classification identified the precuneus with high classification accuracy for stratifying recovery trajectories. Transcriptomic mapping implicated dysregulated synaptic signaling genes in regions exhibiting FC abnormalities. CONCLUSIONS: The authors' investigation delineated a critical role for hypothalamic-cortical circuits in post-SCI motor recovery. The dynamic reconfiguration of hypothalamic-SMA connectivity, coupled with its prognostic value, positions this pathway as a biomarker for monitoring neuroplasticity in SCI.