Regional brain perfusion changes during standard and microburst vagus nerve stimulation in dogs

Vagus nerve stimulation (VNS) is an effective adjunctive treatment for refractory epilepsy in humans, but its mechanism of action (MOA) and optimal stimulation parameters are still unknown. Functional neuroimaging studies could provide better insight into the brain structures involved in the activity of VNS, but have not yet been described in dogs. The aim of this study was to investigate the effect of acute VNS on the regional cerebral blood flow (rCBF) in dogs using micro-SPECT (μ-SPECT). Additionally, a novel stimulation paradigm (microburst VNS) was used and compared with standard VNS.

A VNS Therapy System was implanted in ten Beagle dogs. μ-SPECT was performed after sham, standard and microburst VNS in a randomized, cross-over study. Nineteen volumes of interest (VOIs) were semi-quantitatively analysed and perfusion indices (PIs) were calculated. Furthermore, a rostro-caudal gradient (R-C), an asymmetry index (AI) and a cortical-subcortical index (Co-SCo) were determined. The SPECT results after standard and microburst VNS were compared pairwise with sham stimulation.

Acute standard VNS did not cause significant rCBF alterations. Acute microburst VNS caused a significant hypoperfusion in the left frontal lobe (P=0.023) and in the right parietal lobe (P=0.035). Both stimulation paradigms did not cause changes in R-C, AI nor Co-SCo.

Microburst VNS is more potent than standard VNS to modulate the rCBF in the dog. Our results promote further research towards the antiepileptic effect of microburst VNS in dogs and humans.