Dynamic regional homogeneity changes and their genetic correlates in neuropsychiatric systemic lupus erythematosus: a combined transcriptome-neuroimaging study

Neuropsychiatric systemic lupus erythematosus (NPSLE) is characterized by a broad spectrum of neurological and psychiatric manifestations and remains one of the most severe complications of systemic lupus erythematosus. Although previous neuroimaging studies have demonstrated altered spontaneous brain activity in NPSLE, the dynamic properties of these functional alterations and their underlying biological correlates remain largely unknown. Therefore, we aimed to characterize dynamic regional homogeneity (dReHo) alterations in NPSLE and to explore their transcriptomic correlates using an imaging transcriptomic approach. We collected 66 patients with SLE and 33 healthy people from Taizhou People’s Hospital, dividing them into three groups and conducted neuropsychological scale assessment. Dynamic regional homogeneity alterations were identified using resting-state functional MRI. Imaging transcriptomic analysis was performed by spatially correlating the dReHo alteration map with the Allen Human Brain Atlas (AHBA) to identify genes associated with the imaging pattern. Neurotransmitter system and excitatory neuron maps were further correlated with the dReHo alterations. There are seven brain regions (left gyrus rectus, left middle temporal gyrus, left middle occipital gyrus, left precuneus, right middle occipital gyrus, right middle temporal gyrus and right calcarine fissure) exhibited dReHo abnormalities. Functional annotation linked these regions mainly to social cognition and visual processing. Imaging transcriptomic analysis suggested that the spatial pattern of dReHo alterations was associated with genes enriched in chemical synaptic transmission, excitatory neurons, and the visual cortex. Spatial correlations were also observed between the dReHo alterations and several neurotransmitter maps (DAT, 5-HT2A, 5-HT6, GABA, κ-opioid, M1, SV2A, and HDAC) as well as excitatory neuron subclasses (Ex3-Granule-L4 and Ex8-CorticothalProject-L6). This study integrates resting-state fMRI with imaging transcriptomic analyses to characterize the biological correlates of altered brain functional dynamics in NPSLE. The findings identify candidate molecular pathways and neurotransmitter systems associated with dReHo alterations and highlight the potential involvement of the visual cortex in NPSLE. These observations are hypothesis-generating and provide a foundation for future mechanistic and translational studies.