A distinct biomarker of continuous transcutaneous vagus nerve stimulation treatment in major depressive disorder

Tu, Yiheng; Fang, Jiliang; Cao, Jin; Wang, Zengjian; Park, Joel; Jorgenson, Kristen; Lang, Courtney; Li, Jun; Zhang, Guolei; Zhao, Yanyan; Zhu, Bing; Rong, Peijing; Kong, Jian

doi:10.1016/j.brs.2018.01.006

Cited by 77 publications

(66 citation statements)

References 63 publications

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“…This result is consistent with a previous study using the same data set, in which we found that DLPFC rsFC with the rACC significantly increased after Tai Chi [5] . Similar results have been observed after various exercise interventions (Tai Chi, Baduanjin, and stationary cycling) in patients with knee osteoarthritis and after transcutaneous vagus nerve stimulation in patients with depression [33] .…”

Section: Discussionsupporting

confidence: 83%

Altered hypothalamus functional connectivity with limbic system in fibromyalgia and the modulation effect of intervention

Kong¹,

Huang

Liu

et al. 2020

Preprint

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Background: This study aims to investigate the resting state functional connectivity (rsFC) changes of the hypothalamus in Fibromyalgia patients and the modulation effect of effective treatments. Methods: Fibromyalgia patients and matched healthy controls (HC’s) were recruited. Resting state fMRI data were collected from fibromyalgia patients before and after a 12-week Tai Chi intervention and once from HC’s. Results: Data analysis showed that fibromyalgia patients displayed significantly decreased medial hypothalamus (MH) rsFC with the thalamus and amygdala when compared to HC’s at baseline. After the intervention, fibromyalgia patients showed increased (normalized) MH rsFC in the thalamus and amygdala. Effective connectivity analysis showed disrupted MH and thalamus interaction in fibromyalgia, which nonetheless could be partially restored by Tai Chi. Conclusions: Elucidating the role of the diencephalon and limbic system in the pathophysiology and development of fibromyalgia may facilitate the development of new treatment methods for this prevalent disorder. Trial registration: Trial registration ClinicalTrials.gov Identifier: NCT02407665. Registered 3 April 2015 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02407665

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Section: Discussionsupporting

confidence: 83%

Altered hypothalamus functional connectivity with limbic system in fibromyalgia and the modulation effect of intervention

Kong¹,

Huang

Liu

et al. 2020

Preprint

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“…Finally, tVNS could be used to further understand the processes mediating the clinical improvements brought about by VNS in epilepsy and depression, for example the role of arousal-promoting neuromodulatory signaling in improving mood in depressed patients (Grimonprez et al, 2015;Liu et al, 2016;Fang et al, 2017;Tu et al, 2018). In particular, tVNS-induced pupillary and EEG effects in individual patients could possibly predict the future clinical efficacy of invasive VNS and help guide triaging patients into either conservative therapy or surgical implantation of VNS stimulation devices.…”

Section: Vnsmentioning

confidence: 99%

Transcutaneous vagus nerve stimulation in humans induces pupil dilation and attenuates alpha oscillations

Sharon

Fahoum

Nir

2020

Preprint

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Vagus nerve stimulation (VNS) is widely used to treat drug-resistant epilepsy and depression. While the precise mechanisms mediating its long-term therapeutic effects are not fully resolved, they likely involve Locus Coeruleus (LC) stimulation via the nucleus of the solitary tract (NTS) that receives afferent vagal inputs. In rats, VNS elevates LC firing and forebrain noradrenaline (NE) levels, whereas LC lesions suppress VNS therapeutic efficacy. Non-invasive transcutaneous VNS (tVNS) employs electrical stimulation targeting the auricular branch of the vagus nerve at the Cymba Conchae of the ear, but it remains unclear to what extent tVNS mimics VNS. Here, we investigated the short-term effects of tVNS in healthy human male volunteers (n=24) using high-density EEG and pupillometry during visual fixation at rest, comparing short (3.4s) trials of tVNS to sham electrical stimulation at the earlobe (far from the vagus nerve branch) to control for somatosensory stimulation. Although tVNS and sham stimulation did not differ in subjective intensity ratings, tVNS led to robust pupil dilation (peaking 4-5s after trial onset) that was significantly higher than following sham stimulation. We further quantified how tVNS modulates idle occipital alpha (8-13Hz) activity, identified in each participant using parallel factor analysis. We found that tVNS attenuates alpha oscillations to a greater extent than does sham stimulation. Thus, tVNS reliably induces pupillary and EEG markers of arousal beyond the effects of somatosensory stimulation, supporting the hypothesis that it elevates noradrenaline and acetylcholine signaling and mimics invasive VNS.

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“…Indeed, transcutaneous auricular vagus nerve stimulation (taVNS) was developed as a non-invasive variant of VNS where the vagus nerve is stimulated through the skin of the auricle (Fallgatter et al, 2003). Preliminary studies have shown that noninvasive taVNS improves mood (Kraus et al, 2007) and depressive symptoms (Liu et al, 2016;Tu et al, 2018;Wu et al, 2018) similar to invasive VNS. Such improvements could be due to alterations in brain activity in the prefrontal cortex and the limbic system after invasive (Nahas et al, 2007;Pardo et al, 2008) and noninvasive VNS (Badran et al, 2018;Yakunina et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Non-invasive vagus nerve stimulation boosts mood recovery after effort exertion

Ferstl

Teckentrup

Lin

et al. 2020

Preprint

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Mood plays an important role in our life which is illustrated by the disruptive impact of aberrant mood states in depression. Although vagus nerve stimulation (VNS) has been shown to improve symptoms of depression, the exact mechanism is still elusive, and it is an open question whether non-invasive VNS could be used to swiftly and robustly improve mood. Here, we investigated the effect of left- and right-sided transcutaneous auricular VNS (taVNS) versus a sham control condition on mood after exertion of physical and cognitive effort in 82 healthy participants (randomized cross-over design). Using linear mixed-effects and hierarchical Bayesian analyses of mood ratings, we found that 90 min of either left-sided or right-sided taVNS improved positive mood (b = 5.11, 95% credible interval, CI [1.39, 9.01], 9.6% improvement relative to the mood intercept, BF10= 7.69, pLME = .017), yet only during the post stimulation phase. Moreover, lower baseline scores of positive mood were associated with greater taVNS-induced improvements in motivation (r = −.42, 95% CI [−.58, −.21], BF10 = 249). We conclude that taVNS boosts mood after a prolonged period of effort exertion with concurrent stimulation and that acute motivational effects of taVNS are partly dependent on initial mood states. Collectively, our results show that taVNS may help quickly improve affect after a mood challenge, potentially by modulating interoceptive signals contributing to reappraisal of effortful behavior. This suggests that taVNS could be a useful add-on to current behavioral therapies.

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A distinct biomarker of continuous transcutaneous vagus nerve stimulation treatment in major depressive disorder

Abstract: The FC between the bilateral MH and rACC may serve as a potential biomarker for the tVNS state and predict treatment responses. Our results provide insights into the neural modulation mechanisms of continuous tVNS and reveal a potential therapeutic target for MDD patients.

Cited by 77 publications

References 63 publications

Altered hypothalamus functional connectivity with limbic system in fibromyalgia and the modulation effect of intervention

Altered hypothalamus functional connectivity with limbic system in fibromyalgia and the modulation effect of intervention

Transcutaneous vagus nerve stimulation in humans induces pupil dilation and attenuates alpha oscillations

Non-invasive vagus nerve stimulation boosts mood recovery after effort exertion

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