Imaging the functional anatomy of fascicles in the mammalian vagus nerve with neural tracers, electrophysiology and Electrical Impedance Tomography.

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Over the past two decades, electrical stimulation of the nervous system has progressed from an academic research exercise into mainstream medical use. Implanted stimulators in the brain are now used to treat movement disorders and Parkinson's disease; electrical stimulation of the vagus nerve in the neck has been successfully used in reducing the frequency of epileptic seizures. Nerves in the body may be broadly divided into those that supply muscles and sensation in the limbs - "somatic nerves", and the "autonomic" nervous system when nerves supply bodily organs such as the heart, lungs and liver. There is currently great interest in extending the concept of electrical stimulation to treating diseases related to the autonomic nervous system such as diabetes mellitus or rheumatoid arthritis. A convenient autonomic target is the vagus nerve in the neck because it is easily accessible and a small implanted chip could be used to control about a dozen different supplied organs in the chest and abdomen. At the moment, stimulator technology is only available which would activate or suppress the entire nerve to which it is attached. For a nerve like the vagus nerve, this is unfortunate, as organs other than that intended may be stimulated. An example of this is that when patients with epilepsy have vagus nerve stimulation, they become hoarse, because nerves to the vocal cords are inadvertently stimulated.Nerves are organised into internal bundles, termed "fascicles". The organisation of fascicles is well studied for the somatic nervous system but it is almost completely unknown for the vagus and other autonomic nerves. In order to be able to stimulate an organ selectively within the vagus nerve in the future, it is essential to understand how these fascicles are arranged within the nerve, and what their function is. For example, it is not known if any one fascicle within the vagus nerve in the neck supplies an individual organ, or whether these are all mixed together. If they are mixed together, then it will not be possible to stimulate an individual organ with a stimulator in the neck.The purpose of this project will be to investigate the function and anatomy of the fascicles in the vagus nerve in the neck in humans. The anatomy will be studied with specialised dyes (neural tracers) which can be applied to a nerve and then travel up the nerve so that their connection all the way up to the brain is evident on inspection with a microscope. Secondly, the anatomical connection will be studied with a method in which the entire vagus nerve from the neck to its end organ will be cut into fine slices, inspected under a microscope, and a computer will be used to track all the fascicles within the nerve over its entire course. This approach will, for the first time, identify which fascicles in the cervical vagus nerve in the neck are connected to which end organs. Their electrical function may be studied using a fine array of small spike electrodes which can be inserted into the nerve or a new method, fast neural electrical impedance tomography (EIT). It enables production of images of fascicles in the nerve firing and is the only of these four techniques suitable for human use. It requires surgical placement of a flexible rubber cuff around the vagus nerve. This is ethical and practical in patients with epilepsy in whom the vagus nerve in the neck is exposed for insertion of a vagus nerve stimulator.Studies will be initially undertaken in anaesthetised animals with all four methods. The findings from this will be used to inform a final study in human subjects using fast neural EIT. The output of this work will be, for the first time, an atlas of the anatomy and function of the vagus nerve throughout its course. This will provide a unique platform for efforts in the future where the vagus nerve will be stimulated to treat diseases and it will be beneficial to stimulate selected organs in order to avoid side effects.