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

ABSTRACT: Inhibiting fear-related thoughts and defensive behaviors when they are no longer appropriate to the situation is a prerequisite for flexible and adaptive responding to changing environments. Such inhibition of defensive systems is mediated by ventromedial prefrontal cortex (vmPFC), limbic basolateral amygdala (BLA), and brain stem locus-coeruleus noradrenergic system (LC-NAs). Non-invasive, transcutaneous vagus nerve stimulation (tVNS) has shown to activate this circuit. Using a multiple-day single-cue fear conditioning and extinction paradigm, we investigated long-term effects of tVNS on inhibition of low-level amygdala modulated fear potentiated startle and cognitive risk assessments. We found that administration of tVNS during extinction training facilitated inhibition of fear potentiated startle responses and cognitive risk assessments, resulting in facilitated formation, consolidation and long-term recall of extinction memory, and prevention of the return of fear. These findings might indicate new ways to increase the efficacy of exposure-based treatments of anxiety disorders.

SUBMITTER: Szeska C

PROVIDER: S-EPMC6992620 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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

Szeska Christoph C Richter Jan J Wendt Julia J Weymar Mathias M Hamm Alfons O AO

Scientific reports 20200130 1

Inhibiting fear-related thoughts and defensive behaviors when they are no longer appropriate to the situation is a prerequisite for flexible and adaptive responding to changing environments. Such inhibition of defensive systems is mediated by ventromedial prefrontal cortex (vmPFC), limbic basolateral amygdala (BLA), and brain stem locus-coeruleus noradrenergic system (LC-NAs). Non-invasive, transcutaneous vagus nerve stimulation (tVNS) has shown to activate this circuit. Using a multiple-day sin ...[more]

PMID: 32001763

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Project description:ObjectivesTranscutaneous auricular vagus nerve stimulation (taVNS) modulates brain activity and heart function. The induced parasympathetic predominance leads to an increase of heart rate variability (HRV). Knowledge on the corresponding cortical activation pattern is, however, scarce. We hypothesized taVNS-induced HRV increases to be related to modulation of cortical activity that regulates the autonomic outflow to the heart.Materials and methodsIn thirteen healthy subjects, we simultaneously recorded 64-channel electroencephalography and electrocardiography during taVNS. Two taVNS stimulation targets were investigated, i.e., the cymba conchae and inner tragus, and compared to active control stimulation in the anatomical vicinity, i.e., at the crus helicis and outer tragus. We used intermitted stimulation bursts of 25 Hz applied at a periodicity of 1 Hz. HRV was estimated with different time-domain methodologies: standard deviation of RR (SDNN), the root mean squares of successive differences (RMSSD), the percentage of RR-intervals with at least 50 ms deviation from the preceding RR-interval (pNN50), and the difference of consecutive RR intervals weighted by their mean (rrHRV).ResultsThe stimulation-induced HRV increases corresponded to frequency-specific oscillatory modulation of different cortical areas. All stimulation targets induced power modulations that were proportional to the HRV elevation. The most prominent changes that corresponded to HRV increases across all parameters and stimulation locations were frontal elevations in the theta-band. In the delta-band, there were frontal increases (RMSSD, pNN50, rrHRV, SDNN) and decreases (SDNN) across stimulation sites. In higher frequencies, there was a more divers activity pattern: Outer tragus/crus helicis stimulation increased oscillatory activity with the most prominent changes for the SDNN in frontal (alpha-band, beta-band) and fronto-parietal (gamma-band) areas. During inner tragus/cymba conchae stimulation the predominant pattern was a distributed power decrease, particularly in the fronto-parietal gamma-band.ConclusionNeuro-cardiac interactions can be modulated by electrical stimulation at different auricular locations. Increased HRV during stimulation is correlated with frequency-specific increases and decreases of oscillatory activity in different brain areas. When applying specific HRV measures, cortical patterns related to parasympathetic (RMSSD, pNN50, rrHRV) and sympathetic (SDNN) modulation can be identified. Thus, cortical oscillations may be used to define stimulation locations and parameters for research and therapeutic purposes.

Dataset Information

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

Publications

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

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