Vagus Nerve Stimulation Applied with a Rapid Cycle Has More Profound Influence on Hippocampal Electrophysiology Than a Standard Cycle

Abstract

Although vagus nerve stimulation (VNS) is widely used, therapeutic mechanisms and optimal stimulation parameters remain elusive. In the present study, we investigated the effect of VNS on hippocampal field activity and compared the efficiency of different VNS paradigms. Hippocampal electroencephalography (EEG) and perforant path dentate field-evoked potentials were acquired before and during VNS in freely moving rats, using 2 VNS duty cycles: a rapid cycle (7 s on, 18 s off) and standard cycle (30 s on, 300 s off) and various output currents. VNS modulated the evoked potentials, reduced total power of the hippocampal EEG, and slowed the theta rhythm. In the hippocampal EEG, theta (4-8 Hz) and high gamma (75-150 Hz) activity displayed strong phase amplitude coupling that was reduced by VNS. Rapid-cycle VNS had a greater effect than standard-cycle VNS on all outcome measures. Using rapid cycle VNS, a maximal effect on EEG parameters was found at 300 μA, beyond which effects saturated. The findings suggest that rapid-cycle VNS produces a more robust outcome than standard cycle VNS and support already existing preclinical evidence that relatively low output currents are sufficient to produce changes in brain physiology and thus likely also therapeutic efficacy.

The vagus afferent network: emerging role in translational connectomics

“…4 Moreover, VNS decreases field excitatory postsynaptic potential (fEPSP) slope and electroencephalography (EEG) power as well as slows theta rhythms within the hippocampus, thus suggesting a potential effect in decreasing excitability and subsequently seizure generation. 42,43 It is postulated that this effect may, in part, be mediated by noradrenergic signaling to presynaptic a2A-adrenoceptors within the dentate gyrus, which blocks presynaptic release of excitatory neurotransmitters. 10…”

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

“…Studies have been conducted to evaluate the CNS responses to VNS with neural imaging or recording techniques. For example, invasive recordings of unit activity or field potentials have shown VNS-evoked neuronal responses in the nucleus of solitary tract [ 10 ], the locus coeruleus [ 11 ], and the hippocampus [ 12 ]. These techniques offer high neuronal specificity but only cover spatially confined targets.…”

Invasive Neuromodulation for the Treatment of Pediatric Epilepsy

“…One hypothesis that has emerged posits that VNS leads to increased production of neurotrophic factors within limbic structures [39], enhancing neurogenesis which may facilitate the formation of new synapses to rewire aberrant circuitry [47]. VNS may also directly alter seizure frequency by way of decreasing seizure thresholds in amygdala and hippocampal neurons [48] [49,50].…”