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Neural interfaces have great potential to treat disease and disability by modulating the electrical signals within the nervous system. However, whilst neural stimulation is a well-established technique, current neural interfaces are limited by poor recording ability. Low signal amplitudes necessitate the use of highly invasive techniques that divide or penetrate the nerve, and as such are unsuitable for chronic implantation. In this paper, we present the first application of the velocity selective recording technique to the detection of respiration activity in the vagus nerve, which is involved with treatments for epilepsy, depression, and rheumatoid arthritis. Further, we show this using a chronically implantable interface that does not divide the nerve. We also validate our recording setup using electrical stimulation and we present an analysis of the recorded signal amplitudes. The recording interface was formed from a cuff containing ten electrodes implanted around the intact right vagus nerve of a Danish Landrace pig. Nine differential amplifiers were connected to adjacent electrodes, and the resulting signals were processed to discriminate neural activity based on conduction velocity. Despite the average single channel signal-to-noise ratio of-5.8 dB, it was possible to observe distinct action potentials travelling in both directions along the nerve. Further, contrary to expectation given the low signal-to-noise ratio, we have shown that it was possible to identify afferent neural activity that encoded respiration. The significance of this is the demonstration of a chronically implantable method for neural recording, a result that will transform the capabilities of future neuroprostheses.

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Background: Vagus nerve stimulation is a treatment for refractory epilepsy. The vagus nerve carries parasympathetic information and innervates multiple organs. As seizures are commonly associated with autonomic manifestations, we believe that biomarkers for diseases affecting autonomic functions such as epilepsy can be found in vagus nerve signals. New method: We present a method to record vagus nerve electroneurogram (VENG) and detect in the VENG single unit activity in anesthetized rats during Pentylenetetrazol induced seizures using a true tripolar cuff electrode.Results: The VENG consisted of high amplitude bursts and lower amplitude bursts synchronous to respiration and heartbeat respectively. The average spikes exhibited a triphasic shape with duration below 1.5ms and root mean square amplitude varied between 5.5 +/-0.2 μV and 11.4 +/-3.1 μV depending on the type of recording. An increase of the contact distance resulted in a signal amplitude increase. Application of Lidocaine led to a total disappearance of the recorded spontaneous spiking of the nerve. Comparison with existing methods: True tripolar cuff electrodes exhibited a better performance in terms of artefact rejection, stability and reproducibility of the signal compared to commonly used hook electrodes which is of special interest in seizures where important motion and EMG artifacts are expected. Conclusion:We present a new method to record single unit activity of the vagus nerve during acute chemically induced seizures in rats and verified the neural origin of the recorded signals. This recording method might be a powerful tool to develop seizure biomarkers based on VENG.Recently, a new model of VNS has been commercialized (AspireSR), which was designed to exploit ictal tachycardia using a patented cardiac-based seizure-detecting algorithm. The device triggers VNS on the basis of tachycardia. The performance of this automated seizure detection was assessed in a prospective observational multi-site study (Boon et al., 2015). Despite the rather accurate system, the expected additional or potential benefit for patients is still a matter of debate. A possible explanation is that a substantial number of patients do not have ictal tachycardia while this is a basic requirement for this "closed loop" system. However, the abortive effect of on demand VNS, prior or soon after seizure onset is being confirmed by several human and