Olivier Rossel

Vagus nerve stimulation: State of the art of stimulation and recording strategies to address autonomic function neuromodulation

OBJECTIVE Neural signals along the vagus nerve (VN) drive many somatic and autonomic functions. The clinical interest of VN stimulation (VNS) is thus potentially huge and has already been demonstrated in epilepsy. However, side effects are often elicited, in addition to the targeted neuromodulation. APPROACH This review examines the state of the art of VNS applied to two emerging modulations of autonomic function: heart failure and obesity, especially morbid obesity. MAIN RESULTS We report that VNS may benefit from improved stimulation delivery using very advanced technologies. However, most of the results from fundamental animal studies still need to be demonstrated in humans.

The difference between electrical microstimulation and direct electrical stimulation - towards new opportunities for innovative functional brain mapping?

Abstract Both electrical microstimulation (EMS) and direct electrical stimulation (DES) of the brain are used to perform functional brain mapping. EMS is applied to animal fundamental neuroscience experiments, whereas DES is performed in the operating theatre on neurosurgery patients. The objective of the present review was to shed new light on electrical stimulation techniques in brain mapping by comparing EMS and DES. There is much controversy as to whether the use of DES during wide-awake surgery is the ‘gold standard’ for studying the brain function. As part of this debate, it is sometimes wrongly assumed that EMS and DES induce similar effects in the nervous tissues and have comparable behavioural consequences. In fact, the respective stimulation parameters in EMS and DES are clearly different. More surprisingly, there is no solid biophysical rationale for setting the stimulation parameters in EMS and DES; this may be due to historical, methodological and technical constraints that have limited the experimental protocols and prompted the use of empirical methods. In contrast, the gap between EMS and DES highlights the potential for new experimental paradigms in electrical stimulation for functional brain mapping. In view of this gap and recent technical developments in stimulator design, it may now be time to move towards alternative, innovative protocols based on the functional stimulation of peripheral nerves (for which a more solid theoretical grounding exists).

New electrode layout for internal selectivity of nerves

A nerve is an enclosed, cable-like bundle of peripheral axons. Each axon or set of axons carries neural afferent or efferent information. Many applications need to detect or record these specific nervous data inside the nerve but it is a big challenge. The main issue is to achieve a good selectivity inside the nerve without being invasive. In this context, we propose a new layout of multipolar electrode allowing a very high level of spatial selectivity. This electrode has a flat-interface electrode with an array of poles. The idea is to find the best value for the inter-pole distance and the most suitable post processing in order to both improve selectivity in the nerve and reject external parasitic signals. In this preliminary work, we put emphasis on the simulation of the action potential as a method to help the electrode specification.

Model-based design of control modules for neuromodulation devices

Control systems design may be a difficult task when the system to be controlled is complex, poorly understood, and with limited observability. This is often the case of biological or physiological systems. In this paper, we present a model-based control design framework, which is adapted to the design of medical devices. This framework couples a control module, based on a classical PID controller, a model of the medical device, and a physiological model representing the cardiovascular responses to vagus nerve stimulation (VNS). An example is proposed in which the goal of the controller is to regulate instantaneous heart rate in real-time, by modulating the current delivered to the vagus nerve by the neuromodulator in an adaptive manner. Results of the definition of the control system with different controller parameters and for different model configurations are provided, showing the feasibility and usefulness of a model-based design in this context.

A measure of cortico-cortical potentials evoked by 10Hz direct electrical stimulation of the brain and by means of a differential recording mode of electrocorticographic signals

Direct electrical stimulation (DES) at 60 Hz is used to perform real-time functional mapping of the brain during wide-awake neurosurgery. The electrophysiological effects of DES are largely unknown, locally and at a more remote distance. Here, by lowering the DES frequency to 10 Hz and by using a differential recording mode of electro-corticographic (ECoG) signals to improve the focality, we were able to record cortico-cortical evoked potentials easily with standard current amplitude of stimulation (2 mA). DES applied at 10 Hz and differential recording of ECoG could be used to map on-line the connectivity between different sub-cortical and cortical areas with a higher spatial accuracy.Direct electrical stimulation (DES) at 60 Hz is used to perform real-time functional mapping of the brain during wide-awake neurosurgery. The electrophysiological effects of DES are largely unknown, locally and at a more remote distance. Here, by lowering the DES frequency to 10 Hz and by using a differential recording mode of electro-corticographic (ECoG) signals to improve the focality, we were able to record cortico-cortical evoked potentials easily with standard current amplitude of stimulation (2 mA). DES applied at 10 Hz and differential recording of ECoG could be used to map on-line the connectivity between different sub-cortical and cortical areas with a higher spatial accuracy.

Analysis of a baroreflex model for the study of the chronotropic response to vagal nerve stimulation

This paper describes the integration of computational models of the cardiovascular system, the cardiac electrical activity and the baroreceptor reflex of the autonomic nervous system, with a model representing vagal nerve stimulation (VNS). Sensitivity analyses are performed in order to find the model parameters that produce significant effects on heart rate (chronotropic effect). The most significant parameters are adjusted in order to reproduce real data acquired from sheep suffering from heart failure, during VNS periods. Results show the potential of the model to generate realistic chronotropic responses to VNS.

Fascicle-selective multi-contact cuff electrode

Neural recording is one of the main issues to be addressed in order to allow closed-loop functional electrical stimulation systems. Because each fascicle in nerves carry specific information, new sensors providing high spatial selectivity are required for chronic implantable devices. This work aims at evaluating the feasibility of a new device using a highly spatial-selective multi-contact cuff electrode. The proposed electrode configuration is evaluated based on simulations using a model of a nerve comprising multiple fascicles. Study of the electrode selectivity is done and compared with a state-of-the-art electrode designed for the same purpose and shows that activity of two fascicles separated by as little as 1 mm can be distinguished. Implementation challenges and perspectives for such electrodes are also discussed.

Exploring selective neural electrical stimulation for upper limb function restoration

This article introduces a new approach of selective neural electrical stimulation of the upper limb nerves. Median and radial nerves of individuals with tetraplegia are stimulated via a multipolar cuff electrode to elicit movements of wrist and hand in acute conditions during a surgical intervention. Various configurations corresponding to various combinations of a 12-poles cuff electrode contacts are tested. Video recording and electromyographic (EMG) signals recorded via sterile surface electrodes are used to evaluate the selectivity of each stimulation configuration in terms of activated muscles. In this abstract we introduce the protocol and preliminary results will be presented during the conference.

Case report: Remote neuromodulation with direct electrical stimulation of the brain, as evidenced by intra-operative EEG recordings during wide-awake neurosurgery.

http://dx.doi.org/10.1016/j.clinph.2015.11.005 1388-2457/ 2015 International Federation of Clinical Neurophysiology. Real-time functional mapping of the brain with direct electrical stimulation (DES) is used to guide the resection of slow-growing infiltrative tumours during wide-awake surgery. The DES technique reduces the probability of resecting essential areas near or within the tumour (Duffau, 2005). During the neurosurgery, patients perform a number of neuropsychological tests while DES is applied both cortically and subcortically, in order to detect and thus preserve connectivity online. This technique is especially useful for critical white matter pathways. This functional mapping of the area near the tumour enables the removal of as much as noneloquent infiltrated tissue as possible, while minimizing sequelae. The local electrophysiological effects of DES have only been partially characterized. By using electrocorticography and an implanted grid on the surface of the grey matter for pre-surgical planning in drug-resistant epileptic patients, Matsumoto et al. (2004, 2007) observed ‘‘corticocortical” evoked potentials around 10–50 ms after the start of low-frequency DES (1 Hz, 10–12 mA) at a cortical site. The evoked potentials were measured in contiguous cortical areas whose centres were up to three centimetres apart and were linked by axons in the grey matter or in local Ushaped subcortical fibres. In contrast, the propagation of DES and its remote effects have not yet been investigated (Mandonnet et al., 2010; Szelényi et al., 2010). Here, we report on a case of wide-awake surgery for a slowgrowing, right frontal brain tumour in a 33-year-old man. Intraoperative electroencephalographic (iEEG) recording was used to determine whether cortical or subcortical DES can have remote neuromodulatory effects on electrophysiological signals. The volume of the resection was 116.8 cm. DES (60 Hz, with biphasic current: I = 2 mA, pulse duration = 1 ms) was applied at different locations during the recordings (Fig. 1a). iEEG signals were recorded at four scalp sites: three on the contralesional hemisphere (F3, C3 and O1) and one on the ipsilesional hemisphere (O2). An additional reference electrode was placed on the right mastoid. During the recording itself, the Biosemi system’s common-mode sense electrode served as the reference electrode. Electrophysiological signals were sampled at 2048 Hz and acquired with ActiView software. iEEG signals were detrended, and different stimulation periods were determined based on DES induced artefacts. For cortical DES, we obtained 23 periods with durations ranging from 1.3 to 10.2 s, separated by intervals of at least 2.3 s. For subcortical DES, we obtained nine periods with durations ranging from 3.3 to 11.6 s, separated by intervals of at least 5.1 s. Mean spectrograms were first determined (moving window: 500 ms;

Sensitivity of a frequency-selective electrode based on spatial spectral properties of the extracellular AP of myelinated nerve fibers

In the context of functional electrical stimulation, neural recording is one of the main issues. For instance, the control of the limbs in people with motor deficiencies needs information about the muscle lengths and speeds that can be extracted from electroneurograms (ENG) carried on afferent peripheral nerves. The aim of this study is to propose an non-invasive and spatial-selective electrode (because specific informations are carried into different fascicles). To do so, we investigate the spatial properties of an extracellular action potential (AP). This properties are described qualitatively and quantitatively using analytical study on an inhomogeneous an anisotropic nerve model. Then, a spectral analysis on this spatial signal discriminates the different frequency components. Low spatial frequencies represent the global shape of the signal, whereas high frequencies are related to the type of fibers. We show that the latter is rapidly attenuated with the distance and thus, being a local phenomenon, can be used as a selective measurement. Finally, we propose a spatial filtering based on electrode design and an electronic architecture to extract this high frequencies.