Lesion network of oculogyric crises maps to brain dopaminergic transcriptomic signature.

Abstract

Oculogyric crises are acute episodes of sustained, typically upward, conjugate deviation of the eyes. Oculogyric crises usually occur as the result of acute D2-dopamine receptor blockade, but the brain areas causally involved in generating this symptom remain elusive. Here, we used data from 14 previously reported cases of lesion-induced oculogyric crises and employed lesion network mapping to identify their shared connections throughout the brain. This analysis yielded a common network that included basal ganglia, thalamic, and brainstem nuclei, as well as the cerebellum. Comparison of this network with gene expression profiles associated with the dopamine system revealed spatial overlap specifically with the gene coding for dopamine receptor type 2 (DRD2) as defined by a large-scale transcriptomic database of the human brain. Furthermore, spatial overlap with DRD2 and DRD3 gene expression was specific to brain lesions associated with oculogyric crises when contrasted to lesions that led to other movement disorders. Our findings identify a common neural network causally involved in the occurrence of oculogyric crises and provide a pathophysiological link between lesion locations causing this syndrome and its most common pharmacological cause, namely DRD2 blockade.