Cerebral Hemodynamic Correlates of Transcutaneous Auricular Vagal Nerve Stimulation in Consciousness Restoration: An Open-Label Pilot Study.
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SUBMITTER: Yu Y
PROVIDER: S-EPMC8319239 | biostudies-literature | 2021
REPOSITORIES: biostudies-literature
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Cerebral Hemodynamic Correlates of Transcutaneous Auricular Vagal Nerve Stimulation in Consciousness Restoration: An Open-Label Pilot Study.
Yu Yutian Y Yang Yi Y Gan Shuoqiu S Guo Shengnan S Fang Jiliang J Wang Shouyan S Tang Chunzhi C Bai Lijun L He Jianghong J Rong Peijing P
Frontiers in neurology 20210715
This study aimed to preliminarily illustrate the cerebral hemodynamic correlates of transcutaneous auricular vagal nerve stimulation (taVNS) in consciousness restoration. Arterial spin labeling (ASL) was adopted with functional magnetic resonance imaging (fMRI) to measure cerebral blood flow (CBF) changes before and after taVNS in 10 qualified patients with disorders of consciousness (DOC). Before taVNS, five patients responded to auditory stimuli (RtAS), and five did not respond to auditory sti ...[more]
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Project description:Disorders of consciousness (DoC) are the hallmark of severe acquired brain injuries characterized by abnormal activity in important brain areas and disruption within and between brain networks. As DoC's therapeutic arsenal is limited, new potential therapies such as transcutaneous auricular vagal nerve stimulation (taVNS) have recently been explored. The potential of taVNS in the process of consciousness recovery has been highlighted in recent studies with DoC patients. However, it is not clear how taVNS plays a role in the recovery of consciousness. In this article, we first describe the neural correlates of consciousness, the vagus nerve anatomy and functions, along with the results of functional magnetic resonance imaging studies using taVNS. Based on consciousness recovery and taVNS mechanisms, we propose the Vagal Cortical Pathways model. This model highlights four consecutive pathways (A. Lower brainstem activation, B. Upper brainstem activation, C. Norepinephrine pathway, and D. Serotonin pathway) likely to have an impact on patients with a brain injury and DoC. Additionally, we suggest six different mechanisms of action: (1) Activation of the ascending reticular activating system; (2) Activation of the thalamus; (3) Re-establishment of the cortico-striatal-thalamic-cortical loop; (4) Promotion of negative connectivity between external and default mode networks by the activation of the salience network; (5) Increase in activity and connectivity within the external network through the norepinephrine pathway; and (6) Increase in activity within the default mode network through the serotonin pathway. This model aims to explain the potential therapeutic effects that taVNS has on brain activity in the process of consciousness recovery.
| S-EPMC7477388 | biostudies-literature
Project description:Closed-loop (CL) transcutaneous auricular vagal nerve stimulation (taVNS) was officially proposed in 2020. This work firstly reviewed two existing CL-taVNS forms: motor-activated auricular vagus nerve stimulation (MAAVNS) and respiratory-gated auricular vagal afferent nerve stimulation (RAVANS), and then proposed three future CL-taVNS systems: electroencephalography (EEG)-gated CL-taVNS, electrocardiography (ECG)-gated CL-taVNS, and subcutaneous humoral signals (SHS)-gated CL-taVNS. We also highlighted the mechanisms, targets, technical issues, and patterns of CL-taVNS. By reviewing, proposing, and highlighting, this work might draw a preliminary blueprint for the development of CL-taVNS.
| S-EPMC8763674 | biostudies-literature
Project description:Introduction Tinnitus can become a strong stressor for some individuals, leading to imbalance of the autonomous nervous system with reduction of parasympathetic activity. It can manifest itself as sleep disturbances, anxiety and even depression. This condition can be reversed by bioelectrical vagal nerve stimulation (VNS). Conventional invasive VNS is an approved treatment for epilepsy and depression. Transcutaneous VNS (taVNS) stimulating the auricular branch of the vagus nerve has been shown to activate the vagal pathways similarly as an implanted VNS. Therefore, taVNS might also be a therapeutic alternative in health conditions such as tinnitus-related mental stress (TRMS). This retrospective study in 171 TRMS patients reports the clinical features, psychophysiological characteristics, and results of the heart rate variability (HRV) tests before and after test-taVNS. This study also reports the therapy outcomes of 113 TRMS patients treated with taVNS, in combination with standard tinnitus therapy. Methods Diagnostic tinnitus and hearing profiles were defined. To detect possible cardiac adverse effects, test-taVNS with heart rate monitoring as well as pre- and post-stimulation HRV tests were performed. Daily taVNS home therapy was prescribed thereafter. To assess therapeutic usefulness of taVNS, 1-year follow-up outcome was studied. Results of HRV tests were retrospectively analyzed and correlated to diagnostic data. Results The large majority of patients with TRMS suffer from associated symptoms such as sleep disturbances and anxiety. Baseline HRV data showed that more than three quarters of the 171 patients had increased sympathetic activity before test-taVNS. Test-taVNS shifted mean values of different HRV parameters toward increased parasympathetic activity in about 80% of patients. Test-taVNS did not cause any cardiac or other side effects. No significant adverse effects were reported in follow-up questionnaires. Conclusion TRMS is an example of a stress condition in which patients may benefit from taVNS. As revealed by HRV, test-taVNS improved parasympathetic function, most efficiently in patients with a low starting HRV level. Our tinnitus treatment program, including taVNS, effectively alleviated tinnitus stress and handicap. For wider clinical use, there is a great need for more knowledge about the optimal methodology and parameters of taVNS.
| S-EPMC7527536 | biostudies-literature
Project description:BackgroundAbdominal pain and constipation are 2 main symptoms in patients with constipation-predominant irritable bowel syndrome (IBS-C). This study aimed to investigate the effects and possible mechanisms of transcutaneous auricular vagal nerve stimulation (taVNS) in patients with IBS-C.MethodsForty-two patients with IBS-C were randomized into a 4-week sham-taVNS or taVNS treatment. The primary outcomes were complete spontaneous bowel movements per week (CSBMs/week) and visual analog scale (VAS) for abdominal pain. High-resolution anorectal manometry (HRAM) was performed to evaluate anorectal motor and sensory function. Cytokines and brain gut peptides were analyzed in blood samples. ECG was recorded for the assessment of autonomic function.ResultsCompared with sham-taVNS, (a) taVNS increased CSBMs/week (P = 0.001) and decreased VAS pain score (P = 0.001); (b) improved quality of life (P = 0.020) and decreased IBS symptom score (P = 0.001); (c) improved rectoanal inhibitory reflex (P = 0.014) and improved rectal sensation (P < 0.04); (d) decreased a number of proinflammatory cytokines and serotonin in circulation; and (e) enhanced vagal activity (P = 0.040). The vagal activity was weakly correlated with the CSBMs/week (r = 0.391; P = 0.010) and the VAS pain score (r = -0.347; P = 0.025).ConclusionsNoninvasive taVNS improves both constipation and abdominal pain in patients with IBS-C. The improvement in IBS-C symptoms might be attributed to the integrative effects of taVNS on intestinal functions mediated via the autoimmune mechanisms.Trial registrationwww.chictr.org.cn, no. ChiCTR2000029644.FundingNational Natural Science Foundation of China (grant no. 81970538 for FL).
| S-EPMC8410029 | biostudies-literature
Project description:BackgroundTranscutaneous auricular vagus nerve stimulation (taVNS) has recently been explored for the treatment of Disorders of consciousness (DoC) caused by traumatic brain injury. The evidence of taVNS during the consciousness recovery has been recently reported. However, the mechanism of taVNS in the recovery of consciousness is not clear. This study attempts to investigate the effectiveness of taVNS in DoC by means of Coma Recovery Scale-Revised (CRS-R), Magnetic resonance imaging (MRI), Electrophysiology (EEG), and Single-molecular array (Simoa).Methods/designNighty patients with DoC acquired brain injury are randomized into one of three groups receiving sham taVNS or active taVNS (just left and left or right), respectively. Each of the three groups will experience a 40 days cycle (every 10 days for a small period, baseline 2 weeks, intervention 2 weeks, 40 min per day, 5 days per week, then no intervention for 2 weeks, intervention 2 weeks, 40 min per day, and 5 days per week). Primary outcomes (CRS-R) will be recorded five times during every period. Secondary outcomes will be recorded at the first and at the last period [MRI, EEG, Phosphorylated tau (P-tau), and Neurofilament light chain (NFL)]. We will take notes the adverse events and untoward effects during all cycles.DiscussionTranscutaneous auricular vagus nerve stimulation as a painless, non-invasive, easily applied, and effective therapy was applied for treatment of patients with depression and epilepsy several decades ago. Recent progress showed that taVNS has behavioral effects in the consciousness recovery. However, there is no clinical evidence to support the effects of taVNS on brain activity. Therefore, we will design a randomized controlled trial to evaluate the effectiveness and safety of taVNS therapy for DoC, and explore neural anatomy correlated to taVNS during the consciousness recovery. Finally, this protocol also tests some biomarkers along with the recovery of consciousness.Clinical trial registrationChinese Clinical Trial Registry, ChiCTR2100045161. Registered on 9 April 2021.
| S-EPMC10133680 | biostudies-literature
Project description:BackgroundPatients with disorders of consciousness (DoC) are a challenging population prone to misdiagnosis with limited effective treatment options. Among neuromodulation techniques, transcutaneous auricular vagal nerve stimulation (taVNS) may act through a bottom-up manner to modulate thalamo-cortical connectivity and promote patients' recovery. In this clinical trial, we aim to (1) assess the therapeutic clinical effects of taVNS in patients with DoC; (2) investigate the neural mechanisms underlying the effects of its action; (3) assess the feasibility and safety of the procedure in this challenging population; (4) define the phenotype of clinical responders; and (5) assess the long-term efficacy of taVNS in terms of functional outcomes.MethodsWe will conduct a prospective parallel randomized controlled double-blind clinical trial investigating the effects of taVNS as a treatment in DoC patients. Forty-four patients in the early period post-injury (7 to 90 days following the injury) will randomly receive 5 days of either active bilateral vagal stimulation (45 min duration with 30s alternative episodes of active/rest periods; 3mA; 200-300μs current width, 25Hz.) or sham stimulation. Behavioural (i.e., Coma Recovery Scale-Revised, CRS-R) and neurophysiological (i.e., high-density electroencephalography, hd-EEG) measures will be collected at baseline and at the end of the 5-day treatment. Analyses will seek for changes in the CRS-R and the EEG metrics (e.g., alpha band power spectrum, functional connectivity) at the group and individual (i.e., responders) levels.DiscussionThese results will allow us to investigate the vagal afferent network and will contribute towards a definition of the role of taVNS for the treatment of patients with DoC. We aim to identify the neural correlates of its action and pave the way to novel targeted therapeutic strategies.Clinical trial registrationClinicaltrials.gov n° NCT04065386.
| S-EPMC9712558 | biostudies-literature
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.
| S-EPMC8005577 | biostudies-literature
Project description:Neonates born premature or who suffer brain injury at birth often have oral feeding dysfunction and do not meet oral intake requirements needed for discharge. Low oral intake volumes result in extended stays in the hospital (>2 months) and can lead to surgical implant and explant of a gastrostomy tube (G-tube). Prior work suggests pairing vagus nerve stimulation (VNS) with motor activity accelerates functional improvements after stroke, and transcutaneous auricular VNS (taVNS) has emerged as promising noninvasive form of VNS. Pairing taVNS with bottle-feeding rehabilitation may improve oromotor coordination and lead to improved oral intake volumes, ultimately avoiding the need for G-tube placement. We investigated whether taVNS paired with oromotor rehabilitation is tolerable and safe and facilitates motor learning in infants who have failed oral feeding. We enrolled 14 infants [11 premature and 3 hypoxic-ischemic encephalopathy (HIE)] who were slated for G-tube placement in a prospective, open-label study of taVNS-paired rehabilitation to increase feeding volumes. Once-daily taVNS was delivered to the left tragus during bottle feeding for 2 weeks, with optional extension. The primary outcome was attainment of oral feeding volumes and weight gain adequate for discharge without G-tube while also monitoring discomfort and heart rate (HR) as safety outcomes. We observed no adverse events related to stimulation, and stimulation-induced HR reductions were transient and safe and likely confirmed vagal engagement. Eight of 14 participants (57%) achieved adequate feeding volumes for discharge without G-tube (mean treatment length: 16 ± 6 days). We observed significant increases in feeding volume trajectories in responders compared with pre-stimulation (p < 0.05). taVNS-paired feeding rehabilitation appears safe and may improve oral feeding in infants with oromotor dyscoordination, increasing the rate of discharge without G-tube, warranting larger controlled trials.
| S-EPMC7093597 | biostudies-literature
Project description:Transcutaneous auricular vagus nerve stimulation (taVNS) is a promising noninvasive technique with potential beneficial effects on human emotion and cognition, including cortical arousal and alertness. However, it remains unclear how taVNS could improve cortical arousal and alertness, which are crucial for consciousness and daily task performance. Here, we aimed to estimate the modulatory effect of taVNS on cortical arousal and alertness and to reveal its underlying neural mechanisms. Sixty subjects were recruited and randomly assigned to either the taVNS group (receiving taVNS for 20 min) or the control group (receiving taVNS for 30 s). The effects of taVNS were evaluated behaviorally using a cue-target pattern task, and neurologically using a resting-state electroencephalogram (EEG). We found that taVNS facilitated the reaction time for the targets requiring right-hand responses and attenuated high-frequency alpha oscillations under the close-eye resting state. Importantly, taVNS-modulated alpha oscillations were positively correlated with the facilitated target detection performance, i.e., reduced reaction time. Furthermore, microstate analysis of the resting-state EEG when the eyes were closed illustrated that taVNS reduced the mean duration of microstate C, which has been proven to be associated with alertness. Altogether, this work provided novel evidence suggesting that taVNS could be an enhancer of both cortical arousal and alertness.
| S-EPMC9859411 | biostudies-literature
Project description:Vagus nerve stimulation (VNS) facilitates weight loss in animals and patients treated with VNS for depression or epilepsy. Likewise, chronic transcutaneous auricular VNS (taVNS) reduces weight gain and improves glucose tolerance in Zucker diabetic fatty rats. If these metabolic effects of taVNS observed in rats translate to humans is unknown. Therefore, the hypothesis of this study was that acute application of taVNS affects glucotropic and orexigenic hormones which could potentially facilitate weight loss and improve glucose tolerance if taVNS were applied chronically. In two single-blinded randomized cross-over protocols, blood glucose levels, plasma concentrations of insulin, C-peptide, glucagon, leptin, and ghrelin, together with heart rate variability and baroreceptor-heart rate reflex sensitivity were determined before and after taVNS (left ear, 10 Hz, 300 µs, 2.0-2.5 mA, 30 min) or sham-taVNS (electrode attached to ear with the stimulator turned off). In a first protocol, subjects (n = 16) were fasted throughout the protocol and in a second protocol, subjects (n = 10) received a high-calorie beverage (220 kCal) after the first blood sample, just before initiation of taVNS or sham-taVNS. No significant effects of taVNS on heart rate variability and baroreceptor-heart rate reflex sensitivity and only minor effects on glucotropic hormones were observed. However, in the second protocol taVNS significantly lowered postprandial plasma ghrelin levels (taVNS: -115.5 ± 28.3 pg/ml vs. sham-taVNS: -51.2 ± 30.6 pg/ml, p < 0.05). This finding provides a rationale for follow-up studies testing the hypothesis that chronic application of taVNS may reduce food intake through inhibition of ghrelin and, therefore, may indirectly improve glucose tolerance through weight loss.
| S-EPMC9020171 | biostudies-literature