NEUROIMAGING-GENETIC SIGNATURES OF DISRUPTED SENSORY INTEGRATION IN JUVENILE FIBROMYALGIA

Juvenile fibromyalgia (JFM) is associated with sensory processing dysfunctions and large-scale brain network re-organization. While functional connectivity changes have been described, the neurogenetic mechanisms underlying these alterations remain unclear. Here, we investigated whether disrupted sensory-to-heteromodal connectomic streams in adolescents with JFM spatially overlap with fibromyalgia (FM)-related gene expression from the Allen Human Brain Atlas (AHBA). Forty-six adolescent girls with JFM (16.44±1.11 years) and forty-three healthy girls (16.09±1.06 years) completed validated symptom questionnaires and underwent resting-state fMRI. We applied stepwise functional connectivity (SFC) to characterize connectomic trajectories from sensory brain regions to the default mode network (DMN) across varying "link-step" distances. To investigate neuroimaging-genetic associations, we leveraged the AHBA on a region-wise neurogenetic basis using the Desikan–Killiany atlas to extract cortical expression of FM-related genes (SLC6A4, TRPV2, NRXN3 and MYT1L). Spatial co-localization analyses were performed between AHBA gene expression maps and symptom-related SFC maps, using null-hypothesis distribution curves derived from 20,737 genes (>1.96 SD, p<0.05) for statistical assessment. Across groups, SFC revealed a conserved hierarchical organization progressing from primary to secondary sensory regions, multimodal integration areas, and heteromodal cortices (DMN). Within the JFM group, greater symptom severity was associated with reduced second-step connectivity between secondary somatosensory cortices and the right anterior insula/pars opercularis. We also found that these regions spatially overlapped with cortical areas exhibiting overexpression of the MYT1L gene. Collectively, these findings indicate convergent symptom-related disruptions in multisensory integration pathways in JFM that spatially overlap with cortical regions of MYT1L overexpression, highlighting a potential gene-brain-behavior association.