Vagal nerve stimulation triggers widespread responses and alters large-scale functional connectivity in the rat brain

Abstract

Vagus nerve stimulation (VNS) is a therapy for epilepsy and depression. However, its efficacy varies and its mechanism remains unclear. Prior studies have used functional magnetic resonance imaging (fMRI) to map brain activations with VNS in human brains, but have reported inconsistent findings. The source of inconsistency is likely attributable to the complex temporal characteristics of VNS-evoked fMRI responses that cannot be fully explained by simplified response models in the conventional model-based analysis for activation mapping. To address this issue, we acquired 7-Tesla blood oxygenation level dependent fMRI data from anesthetized Sprague–Dawley rats receiving electrical stimulation at the left cervical vagus nerve. Using spatially independent component analysis, we identified 20 functional brain networks and detected the network-wise activations with VNS in a data-driven manner. Our results showed that VNS activated 15 out of 20 brain networks, and the activated regions covered >76% of the brain volume. The time course of the evoked response was complex and distinct across regions and networks. In addition, VNS altered the strengths and patterns of correlations among brain networks relative to those in the resting state. The most notable changes in network-network interactions were related to the limbic system. Together, such profound and widespread effects of VNS may underlie its unique potential for a wide range of therapeutics to relieve central or peripheral conditions.

Vagal Nerve Stimulation Attenuates Ischemia-Reperfusion Induced Retina Dysfunction in Acute Ocular Hypertension

“…The present study has several limitations. First, previous studies have reported that the frequency of cervical VNS used in different I/R injuries ranges from 2 to 20 Hz (Cao et al, 2017; Stauss, 2017; Mirza et al, 2018). In the present study, we evaluated the effect of VNS at 5 Hz in the retinal I/R model.…”

Stress and Tinnitus; Transcutaneous Auricular Vagal Nerve Stimulation Attenuates Tinnitus-Triggered Stress Reaction

“…When the stimulation patterns and dynamics of functional networks during VNS were examined by fMRI, the vagus nerve was found to convey signals to the brain through the polysynaptic neuronal pathways, by projecting to the brainstem nuclei (NTS, locus coeruleus), subcortical areas and lastly to the cortex (Henry, 2002;Ressler and Mayberg, 2007), thus covering the entire CAN. fMRI and a spatially independent component analysis were utilized in a recent experimental study (Cao et al, 2017). That study demonstrated that VNS activated 15 out of 20 brain networks and that the activated regions covered > 75% of the brain volume.…”

MRI Powered and Triggered Current Stimulator for Concurrent Stimulation and MRI

“…The fMRI data were processed using Analysis of Functional Neuroimages (AFNI, [37]) and the FMRIB Software Library (FSL, [38]). The fMRI data were first corrected for motion and slice timing before being spatially smoothed as per one of the prior works [9], [39]. The fMRI time series were detrended by regressing out the linear trend voxel by voxel.…”