Profiling the neurobiology underlying brain structure in living human subjects

A singular goal of neuroscience is to advance knowledge of the processes whereby neurobiology gives rise to human brain function. The anatomical structure of the human brain is believed to be a critical component of these processes, but surprisingly to date there have been no large-scale studies of the relationship between neurobiology and brain structure in living humans. Such studies have not been performed due to the inability to obtain brain tissue samples from living human cohorts. The Living Brain Project (LBP) was designed to overcome this limitation of human brain research by obtaining tissue samples from the dorsolateral prefrontal cortex (dlPFC) for molecular research in a large cohort of living subjects who undergo multimodal neuroimaging as deep brain stimulation (DBS) patients. Through having access to both brain tissue and neuroimaging we can look at the molecular profiles of brain structure in living human subjects. The following was done for samples from 171 individuals in the LBP. Structural MRI (sMRI) images were taken as part of patient's clinical work up. Those images were then taken and processed using freesurfer for metrics including thickness, volume and area. Tissue from the dlPFC was collected during DBS surgeries. RNA sequencing (RNAseq) was performed on these samples. For each imaging feature differential expression (DE) was performed using dream. Integration of RNAseq with sMRI data from the same individuals identified genes whose levels of expression associated with imaging metrics of the dlPFC including cortical thickness, volume and area. This study represents the first attempt to connect genomics with brain structure in living people and marks an important step towards gaining a more complete picture of the molecular processes underlying human brain function. This analysis significantly contributes to the body of work that attempt to generate a complete picture of the molecular properties that play a role in brain anatomy. Utilizing the LBP, we provide what is, to our knowledge, the most extensive characterization of the molecular profiles of brain structure.