Gene expression patterns decompose fMRI activation in a sub-region-specific manner in mice after nociceptive stimulation

The results of functional magnetic resonance imaging (fMRI) cannot be interpreted directly at the molecular or genetic level. Our integrative workflow aims to add such a new dimension to the functional interpretation using a publicly available mouse brain gene expression database from the Allen Institute for Brain Science (ABA). From an average of 164 in-house measured mouse thermal pain fMRI datasets, we identified the top and bottom 5% of voxels according to their activation probability (AP) in response to warm and hot hind paw stimulation. Here, we investigated whether high AP voxels differ from low AP voxels in terms of gene expression: Analyzing nine core brain regions of the pain/saliency system, the top (high AP) and bottom (low AP) 5% of voxels showed distinct gene expression profiles. In nearly all regions, only high AP voxels were significantly enriched for gene ontology (GO) terms related to neurotransmitter activity, synaptic structure and neuronal function, while only the dorsal striatum showed GO term enrichment in low AP voxels. Notably, randomly selected voxels showed no significant enrichment, demonstrating the reliability of this approach. These results highlight the potential of gaining knowledge by integrating gene expression and fMRI data. Despite the limitations of using fixed gene expression data from the ABA cohort, this approach may provide new insights into physiological processes and improve the parcellation and interpretation of imaging data.