Transcutaneous auricular vagus nerve stimulation in treating major depressive disorder

Wu, Chunxiao; Liu, Peihui; Fu, Huaili; Chen, Wentao; Cui, Shaoyang; Lu, Liming; Tang, Chunzhi

doi:10.1097/md.0000000000013845

“…A functional dissociation of taVNS-induced effects is clinically relevant because cost-evidence accumulation is affected by escitalopram, a selective serotonin reuptake inhibitor and common antidepressant drug 33 . Thus, anti-depressive effects of VNS 27 – 29 , 52 , 53 may act via a different neurobehavioral mechanism on the utility of effort than the commonly used antidepressant, pointing to the potential of complementing currently used pharmacological treatment regimens 54 . Notwithstanding, this hypothesis calls for future research in patients suffering from deficits in invigorating goal-directed behavior 55 .…”

Section: Discussionmentioning

confidence: 99%

Vagus nerve stimulation boosts the drive to work for rewards

Neuser

¹

,

Teckentrup

²

,

Kühnel

³

et al. 2020

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Interoceptive feedback transmitted via the vagus nerve plays a vital role in motivation by tuning actions according to physiological needs. Whereas vagus nerve stimulation (VNS) reinforces actions in animals, motivational effects elicited by VNS in humans are still largely elusive. Here, we applied non-invasive transcutaneous auricular VNS (taVNS) on the left or right ear while participants exerted effort to earn rewards using a randomized cross-over design (vs. sham). In line with preclinical studies, acute taVNS enhances invigoration of effort, and stimulation on the left side primarily facilitates invigoration for food rewards. In contrast, we do not find conclusive evidence that acute taVNS affects effort maintenance or wanting ratings. Collectively, our results suggest that taVNS enhances reward-seeking by boosting invigoration, not effort maintenance and that the stimulation side affects generalization beyond food reward. Thus, taVNS may enhance the pursuit of prospective rewards which may pave avenues to treat motivational deficiencies.

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“…This functional dissociation of taVNS-induced effects is clinically relevant because cost-evidence accumulation is affected by escitalopram, a selective serotonin reuptake inhibitor and common antidepressant drug (Meyniel et al, 2016). Thus, antidepressive effects of VNS (Fang et al, 2016;Grimonprez et al, 2015;Hein et al, 2013;Liu et al, 2016;Tu et al, 2018;Wu et al, 2018;Yuan, Li, Sun, Arias-Carrion, & Machado, 2016) may act via a different neurobehavioral mechanism on the utility of effort than commonly used anti-depressant, pointing to the potential of complementing currently used pharmacological treatment regimes (Argyropoulos & Nutt, 2013).…”

Section: Discussionmentioning

confidence: 99%

Vagus nerve stimulation increases vigor to work for rewards

Neuser

¹

,

Teckentrup

²

,

Kuehnel

³

et al. 2019

Preprint

4

23

1

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Interoceptive feedback transmitted via the vagus nerve plays a vital role in motivation by tuning actions according to physiological needs. Whereas vagus nerve stimulation (VNS) reinforces actions and enhances dopamine transmission in animals, motivational effects elicited by VNS in humans are still largely elusive. Here, we applied non-invasive transcutaneous auricular VNS (taVNS) on the left or the right ear using a randomized cross-over design (vs. sham). During stimulation, 81 healthy participants had to exert effort to earn food or monetary rewards. We reasoned that taVNS enhances motivation and tested whether it does so by increasing prospective benefits (i.e., vigor) or reducing costs of action (i.e., maintenance) compared to sham stimulation. In line with preclinical studies, taVNS generally enhanced invigoration of effort (p = .004, Bayes factor, BF10 = 7.34), whereas stimulation on the left side primarily facilitated vigor for food rewards (left taVNS: Stimulation × Reward Type, p = .003, BF10 = 11.80). In contrast, taVNS did not affect effort maintenance (ps ≥ .09, BF10 < 0.52). Critically, during taVNS, vigor declined less steeply with decreases in wanting (∆b = -.046, p = .031) indicating a boost in the drive to work for rewards. Collectively, our results suggest that taVNS enhances reward-seeking by boosting vigor, not effort maintenance and that the side of the stimulation affects generalization beyond food reward. We conclude that taVNS may enhance the pursuit of prospective rewards which may pave new avenues for treatment of motivational deficiencies. taVNS increases vigor Neuser et al.3

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“…It is reported that auricular concha is the only area on the body surface that is distributed with ear vagus nerve fiber endings ( Peuker and Filler, 2002 ). Inspired by the mechanism of VNS, we and other researchers have proven that transcutaneous auricular vagus nerve stimulation (taVNS), a non-invasive method, also has a curative effect on depression ( Rong et al, 2016 ; Wu et al, 2018 ). Additionally, the brain loci activated by VNS and taVNS are coincident ( Badran et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Transcutaneous Auricular Vagus Nerve Stimulation at 20 Hz Improves Depression-Like Behaviors and Down-Regulates the Hyperactivity of HPA Axis in Chronic Unpredictable Mild Stress Model Rats

Li

¹

,

Wang

²

,

Gao

³

et al. 2020

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Transcutaneous auricular vagus nerve stimulation (taVNS) has gained growing interest as a non-invasive and non-pharmacologic treatment option in various neurological and psychiatric disorders. Animal experiments and clinical trials confirm that taVNS at the auricular concha region has beneficial effects on depression. However, stimulation frequencies are selected empirically, and there is no evidence showing that any frequency is superior to the others. This study explores antidepressant-like effects of three frequencies of taVNS on rats subjected to chronic unpredictable mild stress (CUMS). Sprague-Dawley rats were randomly divided into five groups, i.e., the control, CUMS, 5 Hz-taVNS, 20 Hz-taVNS, and 100 Hz-taVNS groups. The three different frequencies were administered during the 30-min taVNS procedure once a day for 28 consecutive days. Rats exposed to CUMS showed signs of depression-like behaviors, including reduction in sucrose preference and increased immobility time in forced swimming and open field tests as well as significant dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis as detected by plasma corticosterone and adrenocorticotropic hormone concentration. The 28 days’ taVNS sessions with three frequencies elicited quite different consequences. Although 20 Hz taVNS significantly reversed the depression-like behaviors and downregulated the hyperactivity of the HPA axis, neither 5 nor 100 Hz showed any antidepressant-like effect on CUMS-induced rat behavior. Based on these results, we propose that, out of the three frequencies for taVNS intervention on depression, 20 Hz may be the optimized frequency to have a better modulation effect on HPA axis function by activating the auricular vagus nerve.

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Transcutaneous auricular vagus nerve stimulation in treating major depressive disorder

Abstract: Supplemental Digital Content is available in the text

Cited by 56 publications

References 28 publications

Vagus nerve stimulation boosts the drive to work for rewards

Vagus nerve stimulation boosts the drive to work for rewards

Vagus nerve stimulation increases vigor to work for rewards

Transcutaneous Auricular Vagus Nerve Stimulation at 20 Hz Improves Depression-Like Behaviors and Down-Regulates the Hyperactivity of HPA Axis in Chronic Unpredictable Mild Stress Model Rats

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