Despite established individual associations of poor sleep quality and obesity with multimorbidity, their potential joint association remains inadequately c

Objective: The central pathophysiology of chronic low back pain (CLBP) secondary to lumbar disc herniation (LDH) remains poorly understood, particularly the link between macroscale brain network dysfunction and its microscale biological underpinnings. This study aimed to bridge this critical gap by integrating resting-state fMRI, graph theory, and imaging transcriptomics. Methods: Resting-state fMRI data were acquired from 62 CLBP patients with LDH and 67 matched healthy controls (HCs). Whole-brain functional networks were constructed for each participant by calculating functional connectivity (FC) between 90 anatomical regions. Graph theoretical analysis was employed to derive global and nodal topological metrics. Group differences were identified and correlated with clinical variables. Crucially, these neuroimaging phenotypes were spatially mapped against the Allen Human Brain Atlas (AHBA) to uncover potential spatial molecular vulnerabilities. Results: At the connectional level, CLBP patients with LDH exhibited widespread hypoconnectivity across sensorimotor, ventral attention, and default mode networks. Further topological analysis revealed a profound focal degradation of hub function in the cingulate cortex, characterized by significantly reduced nodal degree, efficiency, and betweenness centrality ( p < 0.001), alongside decreased nodal efficiency in the right supplementary motor area, while global network architecture was preserved. Critically, these deficits in cingulate hub topology were significantly correlated with pain intensity. Imaging transcriptomics linked this focal topological failure to genes enriched for neuroinflammatory and synaptic plasticity pathways. Conclusion: These findings reveal multi-level functional network alterations in CLBP with LDH, linking focal hub failure to potential spatial molecular vulnerabilities associated with neuroinflammation and synaptic remodeling.

Background: Migraine is a prevalent and disabling neurological disorder. Resting-state functional magnetic resonance imaging (rs-fMRI) studies have investigated regional intrinsic neural activity alterations in migraine but have often yielded inconsistent findings. Emerging network perspectives suggest that brain disorders may be better understood through disruptions in large-scale networks. Methods: This systematic review included 31 rs-fMRI studies (1,238 migraine patients; 1,005 controls; 302 altered ALFF/ReHo coordinates) to clarify these discrepancies. Using functional connectivity network mapping (FCNM) with Human Connectome Project data (n = 1,093), we identified that heterogeneous regional intrinsic neural activity alterations in migraine converge onto common brain functional networks. Spatial relationships between the identified brain networks and the distribution of major neurotransmitter receptors/transporters were subsequently characterized using the Juspace toolbox. Results: FCNM analysis revealed that heterogeneous regional intrinsic neural activity alterations reported in migraine studies mapped to common brain functional networks, particularly within visual, somatomotor, and attention systems. The FCNM-identified migraine network exhibited significant spatial correlations with normative distributions of metabotropic glutamate receptor 5 (mGluR5), 5-hydroxytryptamine receptor 2A (5-HT2A), and noradrenaline transporter (NAT). Conclusion: These findings suggest that intrinsic neural dysfunctions in migraine map to large-scale networks with multi-neurochemical susceptibility. This framework suggests that heterogeneous regional intrinsic activity alterations in migraine are preferentially connected to visual, somatomotor, and attentional systems and are spatially aligned with normative neurochemical maps. These findings are hypothesis-generating and should not be interpreted as evidence of causality or patient-specific receptor alterations.