Abstract Details

Demonstration that fascicles in the cervical vagus nerve in pigs and humans are organotypically organised using fast neural Electrical Impedance Tomography (fnEIT) and selective electrical stimulation.

Fast neural Electrical Impedance Tomography (fnEIT) is a method for imaging electrical impedance altered by nervous activity. Images of neuronal activity in the brain or nerve are reconstructed by injecting safe, insensible electrical currents every millisecond using benchtop hardware similar to an EEG machine. Originally developed for imaging circuit activity in the brain, we have recently adapted its use for imaging compound action potential activity in fascicles in the cervical vagus nerve, using a silicone rubber nerve cuff, 4mm in diameter and 10mm long, with two rings of 14 platinum electrodes.

Vagus nerve stimulation (VNS) is widely used for treating epilepsy. It has the potential to treat many other diseases such as depression, rhematoid arthirits or heart failure. However, efficacy is limited as current stimulation is of the entire vagus nerve, so that unwanted side effects occur. This could be reduced by selective stimulation of the 10 or so fascicles which are present in human cervical vagus nerve. However, until recently, their functional specificity was unknown.

In the anaesthetised pig, we have shown that fascicles link to recurrent laryngeal, cardiac, and pulmonary function, using fnEIT and selective electrical stimulation (sVNS). This was validated with micro-computed tomography (microCT) tracing of dissected vagus nerve from its end organ to the neck. Fascicles in EIT images with activity from the 3 organs correlated to microCT data with a centre-of-mass error of 755±372µm (≈25% nerve diameter), and similarly to sVNS (704±323µm). sVNS could selectively modulate physiological activities in the larynx (>10x  baseline EMG), lungs (10.1±4.4% RR), and heart (–38.6±13.7% HR) separately (n=4)1. It has also been possible to identify different fascicles subserving cardiac afferent or efferent function which has potential for the treatment of heart disease2.

Work in progress is the first human studies in which we use similar safety approved vagal nerve cuffs in human patients for acute 30 minute studies while VNS simulators are implanted for epilepsy. So far, selective cardiac efferent neuromodulation (~10% bradycardia) has been observed.

These findings offer a path to improve VNS efficacy in the future by selective stimulation so reducing unwanted side-effects. The same approach could also be used to delineate fascicle function for peripheral nerve reparative surgery.

TitleForenamesSurnameInstitutionLead AuthorPresenter
DrNicoleThompsonUniversity College London
DrKirillAristovichUniversity College London
MrAndrew McEvoyUniversity College London
ProfDavid HolderUniversity College London
Reference
1. Thompson N, Ravagli E, Mastitskaya S, Iacoviello F, Stathopoulou T-R, Perkins J, Shearing P R, Aristovich K and Holder D, 2023, Organotopic organisation of the porcine mid-cervical vagus nerve, Front Neurosci 17 (PMID: 37205051)
2. Thompson N, Ravagli E, Mastitskaya S, Challita R, Hadaya J, Iacoviello F, Shah Idil A, Shearing P R, Ajijola O A, Ardell J L, Shivkumar K, Holder D and Aristovich K , 2024, Towards spatially selective efferent neuromodulation: anatomical and functional organization of cardiac fibres in the porcine cervical vagus nerve, JPhysiol (PMID: 39183636)