Transcutaneous auricular vagus nerve stimulation induces stabilizing modifications in large-scale functional brain networks: towards understanding the effects of taVNS in subjects with epilepsy

Abstract

Transcutaneous auricular vagus nerve stimulation (taVNS) is a novel non-invasive brain stimulation technique considered as a potential supplementary treatment option for subjects with refractory epilepsy. Its exact mechanism of action is not yet fully understood. We developed an examination schedule to probe for immediate taVNS-induced modifications of large-scale epileptic brain networks and accompanying changes of cognition and behaviour. In this prospective trial, we applied short-term (1 h) taVNS to 14 subjects with epilepsy during a continuous 3-h EEG recording which was embedded in two standardized neuropsychological assessments. From these EEG, we derived evolving epileptic brain networks and tracked important topological, robustness, and stability properties of networks over time. In the majority of investigated subjects, taVNS induced measurable and persisting modifications in network properties that point to a more resilient epileptic brain network without negatively impacting cognition, behaviour, or mood. The stimulation was well tolerated and the usability of the device was rated good. Short-term taVNS has a topology-modifying, robustness- and stability-enhancing immediate effect on large-scale epileptic brain networks. It has no detrimental effects on cognition and behaviour. Translation into clinical practice requires further studies to detail knowledge about the exact mechanisms by which taVNS prevents or inhibits seizures.

Impact of Transcutaneous Auricular Vagus Nerve Stimulation on Large-Scale Functional Brain Networks: From Local to Global

“…After the end of the stimulation, this effect was enduring. This result contrasts findings from the study by von Wrede et al ( 2021 ), where the same enduring effect was observed, but the immediate effect of the stimulation perceived to be reverse (in median a decrease in integration and a increase in segregation). For stability- and robustness-associated network characteristics, we here observed almost no immediate change in assortativity, i.e., in the vulnerability to synchronize.…”

“…In the previous study, the immediate stimulation-induced effect also indicated a decreased vulnerability to synchronize and a decreased stability of the synchronized state. The discrepancies between the current and the study by von Wrede et al ( 2021 ) are possibly the result of our larger group of subjects (30 vs. 14) and the inclusion of subjects with a broader range of different pathologies and etiologies, which also may assist in explaining the larger inter-subject variability of modifications of global network characteristics observed here. Further studies might shed light on the existence of different subgroups of subjects and the influence of such subgroups on taVNS-induced modifications of topological and stability- and robustness-associated network properties.…”

“…On the global network scale, we observed taVNS to modify topological and stability- and robustness-associated network properties in a majority of subjects. In addition, we found these modifications to be enduring even after the end of the stimulation in a sizable subset of subjects (see scenarios b and c ) corroborating results from a previous study (von Wrede et al, 2021 ). Topological network characteristics indicated on average a small stimulation-induced immediate increase in integration and a decrease in segregation of the subjects' evolving functional brain networks.…”

“…Changes in synchronizability indicated an immediate increase of the stability of a potential synchronized state of the networks during taVNS and a more easily perturbed synchronized state after the stimulation. Again, the enduring effect on stability- and robustness-associated network characteristics was comparable to findings from von Wrede et al ( 2021 ) and the immediate effect was different. In the previous study, the immediate stimulation-induced effect also indicated a decreased vulnerability to synchronize and a decreased stability of the synchronized state.…”

“…Following von Wrede et al ( 2021 ), we applied taVNS with individualized stimulation intensities (range: 0.5–5.0 mA, mean 2.2, SD ±1.1) for 1 h in the early afternoon while subjects underwent a continuous 3 h EEG recording. The stimulation phase (“S”; continuous stimulation of the left cymba conchae) was preceded and followed by 1-h pre- and post-stimulation phase (baseline phases “B1” and “B2”).…”