Transcriptomic profiles link corticostriatal microarchitecture to genetics of neurodevelopment and neuropsychiatric risks

Abstract

Abstract Many studies on macroscale organization have focused on only the cerebral cortex or striatum, leaving a large gap in the microstructural gradient of corticostriatal covariance. Here, we partitioned the striatum into seven distinct parcels and computed the microstructural covariance between each parcel and the cerebral cortex using T1-weighted/T2-weighted mapping. We found that corticostriatal microstructural covariance exhibited a microstructural gradient along the anterior-posterior axis of the striatum. The patterns of corticostriatal microstructural covariance are linked to geodesic distance and cell type-specific gene expression profiles, revealing a gradually attenuated relationship along the anterior-posterior axis of the striatum. Linking gene expression profile to corticostriatal microstructural patterns showed that the transcriptional variations in cell type-specific genes are different between the anterior and posterior striatum and suggested that anterior striatum are more enriched in psychiatric disorders. Moreover, at the genetic level, the corticostriatal microarchitecture showed a spatiotemporal trait during neurodevelopment. Finally, we identified the neural circuits from limbic and medial frontal cortex to striatum that contributes to the common neuropsychiatric disorders. Collectively, our findings reveal spatially covarying of transcriptional specializations with microarchitecture of corticostriatal covariance, highlighting the mechanisms underlying that neurodevelopmental corticostriatal circuits may be involved in neuropsychiatric disorders.