PT  - JOURNAL ARTICLE
AU  - Linden Parkes
AU  - Ben Fulcher
AU  - Murat Yücel
AU  - Alex Fornito
TI  - Transcriptional signatures of connectomic subregions of the human striatum
AID  - 10.1101/089458
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 089458
4099  - http://biorxiv.org/content/early/2016/12/11/089458.short
4100  - http://biorxiv.org/content/early/2016/12/11/089458.full
AB  - Functionally distinct regions of the brain are thought to possess a characteristic connectional fingerprint – a profile of incoming and outgoing connections that defines the function of that area. This observation has motivated efforts to subdivide cortical and subcortical areas using their patterns of connectivity. However, it remains unclear whether these connectomically-defined subregions of the brain can be distinguished at the molecular level. Here, we combine high-resolution diffusion-weighted magnetic resonance imaging with comprehensive transcriptomic data to show that connectomically-defined subregions of the striatum carry distinct transcriptional signatures. Using data-driven clustering of diffusion tractography, seeded from the striatum, in 100 healthy individuals, we identify a tripartite organization of the caudate and putamen that comprises ventral, dorsal, and caudal subregions. We then use microarray data of gene expression levels in 19 343 genes, taken from 98 tissue samples distributed throughout the striatum, to accurately discriminate the three connectomically-defined subregions with 80-90% classification accuracy using linear support vector machines. This classification accuracy was robust at the group and individual level. Genes contributing strongly to the classification were enriched for gene ontology categories including dopamine signaling, glutamate secretion, response to amphetamine, and metabolic pathways, and were implicated in risk for disorders such as schizophrenia, autism, and Parkinson’s disease. Our findings highlight a close link between regional variations in transcriptional activity and interregional connectivity in the brain, and suggest that there may be a strong genomic signature of connectomically-defined subregions of the brain.