Electrical Impedance Tomography Imaging of Functional Anatomy and Selective Stimulation of Fascicles Within the Vagus Nerve

Electroceuticals is a relatively new field in which the goal is to treat a wide variety of medical diseases with electrical stimulation of autonomic nerves. A prime target for intervention is the cervical vagus nerve as it is easily surgically accessible and supplies many organs in the neck, thorax and abdomen. It would be desirable to stimulate selectively in order to avoid the off-target effects that currently occur. Until recently, this has not been tried in the past, both because of limitations in available technology but also because, surprisingly, the fascicular organisation of the cervical vagus nerve is almost completely unknown; work has recently been performed in animal models. The aim of this research is to investigate the functional anatomy of fascicles (groups of nerve fibres) in the cervical vagus nerve of humans. This will include defining innervation to the heart, lungs and recurrent laryngeal and, if possible, the oesophagus, stomach, pancreas, liver and gastrointestinal tract. After the specific locations of above groups are identified, it will be possible to direct the stimulation so that only specific organs are affected by the vagus nerve stimulation. In particular, it may be possible to achieve a therapeutic seizure-suppressive effect in Epilepsy with better efficacy, and, at the same time, avoid all side effects normally present because all of the organ functions are altered when the entire nerve gets stimulated.

Our group has pioneered the use of a multi-purpose nerve cuff for imaging activity within nerves with Electrical Impedance Tomography (EIT) and with the ability of spatially-selective neuromodulation. It has been optimised and validated for use in vivo in animal models.

Vagus nerve stimulation (VNS) is currently perform in humans for the treatment of drug-resistant epilepsy and depression. However, VNS as a therapeutic intervention can be expanded to a vast range of therapeutic applications. Ongoing studies and preclinical research indicate promising results in treating cardiovascular disorders and heart failure, lung injury, asthma, sepsis, rheumatoid arthritis, diabetes, obesity, pain management and targeting the anti-inflammatory pathway in general. In addition, selective neuromodulation could be used as a therapeutic approach for the treatment of acute respiratory distress syndrome, predominant currently during the Covid-19 pandemic, which requires the activation of some pathways (cholinergic anti-inflammatory pathway) and not others (pulmonary function) to effectively improve outcomes.

Even with the vast potential of VNS in treating a variety of diseases, limitations still exist. Without the knowledge of the neuroanatomy of the target nerve, side effects prevail and reduce the efficacy of treatment. A large proportion of side-effects frequently experienced, including cough, dyspnoea and hoarseness, can be attributed to activation of the recurrent laryngeal nerve fibres in the vagus nerve. Avoidance of vagal outflow to the larynx alone could greatly improve VNS and reduce the side effects so often observed. However, knowledge of the innervation from all regions within the cervical vagus nerve could further improve targeted stimulation and therapeutic efficacy; avoiding any unwanted responses in non-targeted organs such as shortness of breath and bradycardia and could reduce the risk of further, long-term side effects, such as developing hyperglycaemia when stimulating for epilepsy.

EIT and selective stimulation of the human vagus nerve holds promise to provide information of the fascicular organisation of the nerve which would allow for targeted neuromodulation during the treatment of epilepsy, depression and other disorders without indiscriminate vagal outflow thereby avoiding off-target effects currently experienced. The efficacy and therapeutic outcomes of VNS will be improved. It requires interdisciplinary collaboration from biomedical scientists, electronic engineers and mathematicians, and holds great interest for those interested in interdisciplinary work in these fields.