Multimodal CCA + joint ICA reveals fused gray matter volume and resting-state functional alterations with neurotransmitter associations in Crohn’s disease

Crohn’s disease is a chronic inflammatory bowel disease often accompanied by gut–brain axis dysregulation. However, previous studies have largely relied on single-modality neuroimaging analyses, leaving the covarying structural–functional alterations and their potential relationship with neurotransmitter profiles largely unknown. Structural MRI (gray matter volume, GMV) and resting-state functional MRI (fractional amplitude of low-frequency fluctuations, fALFF) data were acquired from 100 patients with CD and 50 healthy controls. Multimodal canonical correlation analysis combined with joint independent component analysis (mCCA + jICA) was applied to identify cross-modal independent components (ICs), followed by correlation analyses with clinical variables and neurotransmitter spatial mapping using JuSpace. Compared with healthy controls, CD patients exhibited one group-discriminative joint component [GMV IC1 (FDR-corrected P = 0.028) and fALFF IC1 (FDR-corrected P = 0.001); thalamus, default mode network, insula, sensorimotor cortex, occipital lobe, cerebellum, and frontal regions], and one modality-specific group-discriminative component [fALFF IC3 (FDR-corrected P = 0.009); cerebellum and extensive frontal areas]. fALFF IC1 was strongly correlated with fALFF IC3 ( r = 0.883, FDR-corrected P < 0.001). GMV IC1 was negatively correlated with disease activity ( r = − 0.430, FDR-corrected P < 0.001), whereas fALFF IC1 was positively correlated with quality of life ( r = 0.261, FDR-corrected P = 0.031). Spatial mapping revealed correspondence with dopaminergic, serotonergic, noradrenergic, and opioid systems. Our findings suggest structural–functional covariant patterns and their spatial correspondence with normative neurotransmitter distributions in CD, providing preliminary insights into the neurobiological mechanisms underlying the disease.