Sciullo, M. | Search bioRxiv

bioRxiv2021

Selective stimulation of the ferret abdominal vagus nerve with multi-contact nerve cuff electrodes

Dysfunction and diseases of the gastrointestinal (GI) tract are a major driver of medical care. The vagus nerve innervates and controls multiple organs of the GI tract and vagus nerve stimulation (VNS) could provide a means for affecting GI function and treating disease. However, the vagus nerve also innervates many other organs throughout the body, and off-target effects of VNS could cause major side effects such as changes in blood pressure. In this study, we aimed to achieve selective stimulation of populations of vagal afferents using a multi-contact cuff electrode wrapped around the abdominal trunks of the vagus nerve. Four-contact nerve cuff electrodes were implanted around the dorsal (N=3) or ventral (N=3) abdominal vagus nerve in six ferrets, and the response to stimulation was measured via a 32-channel microelectrode array (MEA) inserted into the nodose ganglion. Selectivity was characterized by the ability to evoke responses in MEA channels through one bipolar pair of cuff contacts but not through the other bipolar pair. We demonstrated that is was possible to selectively activate subpopulations of vagal afferents using abdominal VNS. Additionally, we quantified the conduction velocity of evoked responses to determine what types of nerve fibers (i.e. A{delta} vs. C) responded to stimulation. We also quantified the spatial organization of evoked responses in the nodose MEA to determine if there is somatotopic organization of the neurons in that ganglion. Finally, we demonstrated in a separate set of three ferrets that stimulation of the abdominal vagus via a four-contact cuff could selectively alter gastric myoelectric activity, suggesting that abdominal VNS can potentially be used to control GI function.

bioengineering↗

bioRxiv2020

Tuning electrical stimulation of the cervical vagus nerve for abdominal signaling while reducing cardiovascular side effects

Electrical vagus nerve stimulation (VNS) has the potential to treat a wide variety of diseases by modulating afferent and efferent communication to the heart, lungs, esophagus, stomach, and intestines. Although distal vagal nerve branches, close to end organs, could provide a selective therapeutic approach, these locations are often surgically inaccessible. In contrast, the cervical vagus nerve has been targeted for decades using surgically implantable cuff electrodes to treat epileptic seizures and depression; however, to date, clinical implementation of VNS has relied on an electrode with contacts that fully wrap around the nerve, producing non-selective activation of the entire nerve. Here we demonstrate selective cervical VNS using cuff electrodes with multiple contacts around the nerve circumference to target different functional pathways. These flexible probes were adjusted to the diameter of the nerve using an adhesive hydrogel wrap to create a robust electrode interface. Our approach was verified in a rat model by demonstrating that cervical VNS produces neural activity in the abdominal vagus nerve while limiting effects on the cardiovascular system (i.e., changes in heart rate or blood pressure). This study demonstrates the potential for selective cervical VNS as a therapeutic approach for modulating distal nerve branches while reducing off target effects. This methodology could potentially be refined to treat gastrointestinal, metabolic, inflammatory, cardiovascular, and respiratory diseases amenable to vagal neuromodulatory control.

neuroscience↗