Mapping BOLD Activation by Pharmacologically Evoked Tremor in Swine

Harmaline-induced tremor is one of the most commonly utilized disease models for essential tremor (ET). However, the underlying neural networks involved in harmaline-induced tremor and the degree to which these are a representative model of the pathophysiologic mechanism of ET are incompletely understood. In this study, we evaluated the functional brain network effects induced by systemic injection of harmaline using pharmacological functional magnetic resonance imaging (ph-fMRI) in the swine model. With harmaline administration, we observed significant activation changes in cerebellum, thalamus, and inferior olivary nucleus (ION). In addition, inter-regional correlations in activity between cerebellum and deep cerebellar nuclei and between cerebellum and thalamus were significantly enhanced. These harmaline-induced effects gradually decreased with repeated administration of drug, replicating the previously demonstrated 'tolerance' effect. This study demonstrates that harmaline-induced tremor is associated with activity changes in brain regions previously implicated in humans with ET. Thus, harmaline-induction of tremor in the swine may be a useful model to explore the neurological effects of novel therapeutic agents and/or neuromodulation techniques for ET.