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BACKGROUND: In the context of morbid obesity, vagus nerve stimulation could be used to control gastric function targeting the small afferent B-fibers and C-fibers. Compared to large A-fibers, activation thresholds of these small efferent fibers are 10 to 100 times greater, inducing technical constraints and possible nerve damages. Although rectangular waveform is commonly used in nerve stimulation, recent modeling and experimental studies suggest that non-rectangular waveforms could reduced the charge injected by the stimulator. NEW METHOD: The objective of the present study is to evaluate the charge injection of complex waveforms such as the ramp, quarter sine and chopped pulses in the context of vagus nerve stimulation. We performed in-vivo study on the porcine abdominal vagus nerves and evaluated charge injection at activation thresholds. A modeling study was performed to further extent the results obtained in-vivo. COMPARISON WITH EXISTING METHOD: Compared to the rectangular pulse, the ramp and quarter sine waveforms activated gastric fibers with the lowest charge injection: -23.2% and -30.1% respectively. The efficacy of chopped pulses is questioned through the consideration of the strength-duration curve. CONCLUSION: Continuous ramp and quarter sine waveforms effectively activate small diameter fibers. These pulse shapes may be considered for long-term vagus nerve stimulation. The results predicted by computational models were qualitatively consistent with experiments. This suggested the relevance of using modeling in the context of complex waveforms prior to future in-vivo tests.
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Fenómenos Electrofisiológicos/fisiología , Fibras Nerviosas Mielínicas , Fibras Nerviosas Amielínicas , Estimulación del Nervio Vago/métodos , Nervio Vago , Potenciales de Acción/fisiología , Animales , Potenciales Evocados/fisiología , Femenino , Modelos Animales , Modelos Neurológicos , Obesidad/terapia , PorcinosRESUMEN
BACKGROUND: Abdominal bilateral vagal stimulation reduces food intake in animals. However, the classical square wave, mA range current generator is poorly effective to evoke action potentials on A∂ and C neurons that represent the majority of vagal neurons at the abdominal level. OBJECTIVE/HYPOTHESIS: METHODS: The current thresholds for pulsons (S2 & S3) and millisecond pulses (S1) required to trigger action potentials were calculated in 5 anaesthetized pigs using single fibre recording. Similar stimulation protocols were compared chronically to sham stimulation in 24 pigs. After two weeks of chronic stimulation, food intake and brain metabolism were investigated. The electrical characteristics and histology of the vagus nerve were also studied. RESULTS: S3 stimulation required a lower amount of charges to trigger an action potential. Chronically applied S2 & S3 activated the dorsal vagal complex and increased the metabolism of its afferent cortical structures. They also reduced energy intake together with a reduced ingestion of high fat and high sugar diets. All these effects were not observed for the S1 group. The vagal histology for the S1, S2 and S3 groups was not different from that of the sham. CONCLUSIONS: These findings demonstrate that pulsons applied bilaterally on the abdominal vagus reduced food intake as a consequence of the activation of the brainstem and higher-order brain areas.
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Tronco Encefálico/fisiología , Ingestión de Alimentos , Neuronas/fisiología , Nervio Vago/fisiología , Animales , Tronco Encefálico/citología , Tronco Encefálico/diagnóstico por imagen , Tronco Encefálico/metabolismo , Potenciales Evocados , Femenino , Masculino , Neuronas/metabolismo , Tomografía de Emisión de Positrones , Porcinos , Estimulación del Nervio VagoRESUMEN
Acute vagal stimulation modifies glucose and insulin metabolism, but the effect of chronic bilateral vagal stimulation is not known. Our aim was to quantify the changes in whole-body and organ-specific insulin sensitivities 12 weeks after permanent, bilateral, vagal stimulation performed at the abdominal level in adult mini-pigs. In 15 adult mini-pigs, stimulating electrodes were placed around the dorsal and ventral vagi using laparoscopy and connected to a dual-channel stimulator placed subcutaneously. Animals were divided into three groups based on stimulation and body weight (i.e., lean nonstimulated, obese nonstimulated, and obese stimulated). Twelve weeks after surgery, glucose uptake and insulin sensitivity were measured using positron emission tomography during an isoglycemic clamp. Mean whole-body insulin sensitivity was lower by 34% (P < 0.01) and the hepatic glucose uptake rate was lower by 33% (P < 0.01) in obese-nonstimulated mini-pigs but was no different in obese-stimulated compared with lean mini-pigs. An improvement in skeletal glucose uptake rate was also observed in obese-stimulated compared with obese-nonstimulated groups (P < 0.01). Vagal stimulation was associated with increased glucose metabolism in the cingulate and prefrontal brain areas. We conclude that chronic vagal stimulation improves insulin sensitivity substantially in diet-induced obesity by both peripheral and central mechanisms.
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Glucemia/metabolismo , Encéfalo/metabolismo , Resistencia a la Insulina , Hígado/metabolismo , Músculo Esquelético/metabolismo , Obesidad/metabolismo , Estimulación del Nervio Vago , Abdomen , Animales , Peso Corporal , Encéfalo/diagnóstico por imagen , Metabolismo Energético , Glucosa/metabolismo , Técnica de Clampeo de la Glucosa , Hígado/diagnóstico por imagen , Músculo Esquelético/diagnóstico por imagen , Tomografía de Emisión de Positrones , Porcinos , Porcinos EnanosRESUMEN
This article introduces a new approach of selective neural electrical stimulation of the upper limb nerves. Median and radial nerves of individuals with tetraplegia are stimulated via a multipolar cuff electrode to elicit movements of wrist and hand in acute conditions during a surgical intervention. Various configurations corresponding to various combinations of a 12-poles cuff electrode contacts are tested. Video recording and electromyographic (EMG) signals recorded via sterile surface electrodes are used to evaluate the selectivity of each stimulation configuration in terms of activated muscles. In this abstract we introduce the protocol and preliminary results will be presented during the conference.
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OBJECTIVE: Neural signals along the vagus nerve (VN) drive many somatic and autonomic functions. The clinical interest of VN stimulation (VNS) is thus potentially huge and has already been demonstrated in epilepsy. However, side effects are often elicited, in addition to the targeted neuromodulation. APPROACH: This review examines the state of the art of VNS applied to two emerging modulations of autonomic function: heart failure and obesity, especially morbid obesity. MAIN RESULTS: We report that VNS may benefit from improved stimulation delivery using very advanced technologies. However, most of the results from fundamental animal studies still need to be demonstrated in humans.
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Sistema Nervioso Autónomo/fisiología , Fenómenos Fisiológicos del Sistema Nervioso , Estimulación del Nervio Vago/tendencias , Animales , Sistema Nervioso Autónomo/anatomía & histología , Epilepsia/fisiopatología , Humanos , Nervio Vago/fisiologíaRESUMEN
Vagus nerve stimulation (VNS) has been successfully performed in animals for the treatment of different experimental models of inflammation. The anti-inflammatory effect of VNS involves the release of acetylcholine by vagus nerve efferent fibers inhibiting pro-inflammatory cytokines (e.g. TNF-α) produced by macrophages. Moreover, it has recently been demonstrated that splenic lymphocytic populations may also be involved. As anesthetics can modulate the inflammatory response, the current study evaluated the effect of two different anesthetics, isoflurane and pentobarbital, on splenic cellular and molecular parameters in a VNS rat model. Spleens were collected for the characterization of lymphocytes sub-populations by flow cytometry and quantification of cytokines secretion after in vitro activation. Different results were observed depending on the anesthetic used. The use of isoflurane displayed a non-specific effect of VNS characterized by a decrease of most splenic lymphocytes sub-populations studied, and also led to a significantly lower TNF-α secretion by splenocytes. However, the use of pentobarbital brought to light immune modifications in non-stimulated animals that were not observed with isoflurane, and also revealed a specific effect of VNS, notably at the level of T lymphocytes' activation. These differences between the two anesthetics could be related to the anti-inflammatory properties of isoflurane. In conclusion, pentobarbital is more adapted than isoflurane in the study of the anti-inflammatory effect of VNS on an anesthetized rat model in that it allows more accurate monitoring of subtle immunomodulatory processes.
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Anestésicos/farmacología , Estimulación del Nervio Vago , Nervio Vago/efectos de los fármacos , Acetilcolina/metabolismo , Animales , Citocinas/metabolismo , Masculino , Ratas , Ratas Sprague-Dawley , Nervio Vago/metabolismoRESUMEN
Dynamic Causal Modelling (DCM) has been proposed to estimate neuronal connectivity from functional magnetic resonance imaging (fMRI) using a biophysical model that links synaptic activity to hemodynamic processes. However, it is well known that fMRI is sensitive not only to neuronal activity, but also to many other psychophysiological responses which may be task-related, such as changes in cardio-respiratory activity. They are not explicitly taken into account in the generative models of DCM and their effects on estimated neuronal connectivity are not known. The main goal of this study was to report the face validity of DCM in the presence of strong physiological confounds that presumably cannot be corrected for, using an fMRI experiment of vagus nerve stimulation (VNS) performed in rats. First, a simple simulation was used to evaluate the principled ability of DCM to recover directed connectivity in the presence of a confounding factor. Second, we tested the experimental validity using measures of the BOLD correlates of left 5Hz VNS. Because VNS mostly activates the central autonomic regulation system, fMRI signals were likely to represent both direct and indirect vascular responses to such activation. In addition to the inference of standard statistical parametric maps, DCM was thus used to estimate directed neural connectivity in a small brain network including the nucleus tractus solitarius (NTS) known to receive vagal afferents. Though blood pressure changes may constitute a major physiological confound in this dataset, model comparison of DCMs still allowed the identification of the NTS as the input station of the VNS pathway to the brain. Our study indicates that current developments of DCM are robust to psychophysiological responses to some extent, but does not exclude the need to develop specific models of brain - body interactions within the DCM framework to better estimate neuronal connectivity from fMRI time series.