Exploring terra incognita of cognitive science: Lateralization of gene expression at the frontal pole of the human brain

Abstract

Background. Rostral prefrontal cortex, or frontopolar cortex (FPC), also known as Brodmann area 10 (BA10), is the most anterior part of the human brain. It is one of the largest cytoarchitectonic areas of the human brain that has significantly increased its volume during evolution. Anatomically the le (BA10L) and right (BA10R) parts of FPC show slight asymmetries and they may have distinctive cognitive functions. Objective. In the present study, we investigated differential expression of the transcriptome in the le and right parts of BA10. Design. Postmortem samples of human brain tissue from fourteen donors (male/ female without history of psychiatric and neurological diseases, mean age 39.79±3.23 years old, mean postmortem interval 12.10±1.76 h) were obtained using the resources of three institutions: the Partner Institute of Computational Biology of Chinese Academy of Sciences, the Max Planck Institute for Evolutionary Anthropology, and NIH Neuro-BioBank. Results. By using a standard RNA-sequencing followed by bioinformatic analysis, we identified 61 genes with differential expression in the le and right FPC. In general, gene expression was increased in BA10R relative to BA10L: 40 vs. 21 genes, respectively. According to gene ontology analysis, the majority of up-regulated genes in BA10R be- longed to the protein-coding category, whereas protein-coding and non-coding genes were equally up-expressed in BA10L. Most of the up-regulated genes in BA10R were involved in brain plasticity and activity-dependent mechanisms also known for their role in the hippocampus. 24 out of 30 mental disorder-related genes in the dataset were disrupted in schizophrenia. No such a wide association with other mental disorders was found. Conclusion. Discovered differences point at possible causes of hemispheric asymmetries in the human frontal lobes and at the molecular base of higher-order cognitive processes in health and disease.

Keywords

• neuropsychology
• frontopolar cortex
• human cerebral asymmetry
• yakovlevian torque
• RNA transcriptome
• sequencing
• schizophrenia
• attention