Transcutaneous vagus nerve stimulation and extinction of prepared fear: A conceptual non-replication

Abstract

Transcutaneous stimulation of the auricular branch of the vagus nerve (tVNS) may accelerate fear extinction in healthy humans. Here, we aimed to investigate this hypothesis in healthy young participants in a prepared learning paradigm, using spider pictures as conditioned stimuli. After a fear conditioning phase, participants were randomly allocated to receive tVNS (final N = 42) or sham stimulation (final N = 43) during an extinction phase. Conditioned fear was assessed using US expectancy ratings, skin conductance and fear potentiated startle responses. After successful fear acquisition, participants in both groups showed a reduction of fear over the course of the extinction phase. There were no between-group differences in extinction rates for physiological indices of fear. Contrary to previous findings, participants in the tVNS condition also did not show accelerated declarative extinction learning. Participants in the tVNS condition did have lower initial US expectancy ratings for the CS− trials than those who received sham stimulation, which may indicate an enhanced processing of safety cues due to tVNS. In conclusion, the expected accelerated extinction due to tVNS was not observed. The results from this study call for more research on the optimal tVNS stimulation intensity settings.

Transcutaneous Vagus Nerve Stimulation Does Not Affect Verbal Memory Performance in Healthy Volunteers

“…However, it could also be possible that tVNS only interacts with specific memory functions, such as associative memory, and is not able to improve immediate recall or delayed recognition. In 2016, Burger et al investigated the effect of tVNS on fear extinction, a process that is also highly dependent on memory formation (Burger et al, 2016(Burger et al, , 2017(Burger et al, , 2018Verkuil et al, 2017). A significant acceleration of fear extinction learning was seen after tVNS; however, this did not lead to better retention of extinction memory.…”

Promoting long-term inhibition of human fear responses by non-invasive transcutaneous vagus nerve stimulation during extinction training

“…However, the focus of this manuscript firstly lies on the translation of the extinction enhancing effects of vagal stimulation on behavioral indicators of fear, which were found in rodents [18][19][20] . Second, we wanted to replicate previous results in humans, showing extinction enhancing effects of tVNS on cognitive indicators of fear [23][24][25] . Thus, the ECG and SCL data are out of this manuscript's scope.…”

“…While tVNS enhanced extinction of cognitive risk assessments in humans (US expectancy ratings) 23,24 , no effect of tVNS was found for behavioral or physiological measures of fear [23][24][25] . One reason for these mixed findings might be, that previous human research used the same fixed and rather low tVNS intensities for each participant [23][24][25] , not taking individual differences in sensitivity into account that might have resulted in reduced stimulation of the vagus nerve in some subjects. More important, most of these human studies used differential-cue conditioning tasks, while aversive single-cue conditioning was used in animal research.…”

International Consensus Based Review and Recommendations for Minimum Reporting Standards in Research on Transcutaneous Vagus Nerve Stimulation (Version 2020)

“…Predominantly, these studies are characterized by short stimulation periods, addressing the immediate effects. Psychological targets have been broad (though not all of them are sensitive to tVNS), including: experimentally induced worry (Burger et al, 2019a ); post-error slowing (Sellaro et al, 2015b ); attention to fearful faces (Verkuil and Burger, 2019 ); associative memory (Jacobs et al, 2015 ) or single-item word memory (Giraudier et al, 2020 ; Mertens et al, 2020 ); extinction of fear responses or fear conditioning (Burger et al, 2016 , 2017 , 2018 , 2019b ; Genheimer et al, 2017 ; Szeska et al, 2020 ); implicit spiritual self-representations (Finisguerra et al, 2019 ); flow experience (Colzato et al, 2018b ); response selection during sequential action (Jongkees et al, 2018 ) or during action cascading processes (Steenbergen et al, 2015 ); the recognition of emotions in faces or bodies (Colzato et al, 2017 ; Sellaro et al, 2018 ; Koenig et al, 2019 ); divergent thinking (Colzato et al, 2018a ); conflict-triggered adjustment of cognitive control (Fischer et al, 2018 ); auditory selective attention (Rufener et al, 2018 ) or visual selective attention (Ventura-Bort et al, 2018 ); inhibitory control (Beste et al, 2016 ; Borges et al, 2020 ); automatic motor inhibition (Keute et al, 2018 ); cognitive flexibility (Borges et al, 2020 ; Tona et al, 2020 ); prosocial behavior (Sellaro et al, 2015a ) and reward sensitivity (Neuser et al, 2019 ).…”