Bioelectronic medicine for the autonomic nervous system: clinical applications and perspectives

Bioelectronic medicine (BM) is an emerging new approach for developing novel neuromodulation therapies for pathologies that have been previously treated with pharmacological approaches. In this review, we will focus on the neuromodulation of autonomic nervous system (ANS) activity with implantable devices, a field of BM that has already demonstrated the ability to treat a variety of conditions, from inflammation to metabolic and cognitive disorders. Recent discoveries about immune responses to ANS stimulation are the laying foundation for a new field holding great potential for medical advancement and therapies and involving an increasing number of research groups around the world, with funding from international public agencies and private investors. Here, we summarize the current achievements and future perspectives for clinical applications of neural decoding and stimulation of the ANS. First, we present the main clinical results achieved so far by different BM approaches and discuss the challenges encountered in fully exploiting the potential of neuromodulatory strategies. Then, we present current preclinical studies aimed at overcoming the present limitations by looking for optimal anatomical targets, developing novel neural interface technology, and conceiving more efficient signal processing strategies. Finally, we explore the prospects for translating these advancements into clinical practice.

Brain-controlled neuroprosthetic interventions to restore locomotion after contusion spinal cord injury in the rat

Marco Bonizzato

Spinal cord injury (SCI), second only to stroke, is the leading cause of paralysis. Therapies based on electrical stimulation of the spinal cord and other locomotor areas of the Nervous System improve motor control in people with neurotrauma. Neuromodulation of the sensorimotor systems can indeed reactivate circuitries that are left dormant after SCI and turn them into an active locomotor state. These results have been found in animal models and translated to clinical fruition. Recent medical research has demonstrated that the involvement of volition and motor intent is a decisive factor for success of rehabilitation therapies that involve functional electrical stimulation of spinal cord and muscles. A key brain area that encodes information related to the conscious processing and execution of movement is the primary sensory-motor cortex. In this thesis I present two novel neuroprosthetic systems for neuromodulation based on cortical population activity in rats with SCI. We tested the hypotheses that neurons in the motor cortex could provide a reliable input for closed-loop neuroprosthetic systems designed to electrically stimulate different locomotor areas of the nervous system in a locomotor-phase-specific manner and thus enhance the locomotor output. During the experiments, we connected cortical correlates of intended movements with patterns of stimulation delivered either at the midbrain or at the sublesional spinal cord. Our brain-controlled functional stimulation reduced locomotor deficits caused by spinal cord injury and restored voluntary control of foot movement. These findings and the control policies we developed could be applied to clinical trials to improve the results of neurorehabilitation, for the benefit of people living with SCI.

EPFL2017

Soft, Implantable Bioelectronic Interfaces for Translational Research

Beatrice Barra, Jocelyne Bloch, Simon Borgognon, Marco Capogrosso, Grégoire Courtine, Florian Dylan Fallegger, Ivan Furfaro, Sébastien Jiguet, Xiaoyang Kang, Stéphanie Lacour, Evgenia Vladimirova Roussinova, Andreas Rowald, Giuseppe Schiavone, Ismael Seanez Gonzalez, Nicolas Vachicouras

The convergence of materials science, electronics, and biology, namely bioelectronic interfaces, leads novel and precise communication with biological tissue, particularly with the nervous system. However, the translation of lab‐based innovation toward clinical use calls for further advances in materials, manufacturing and characterization paradigms, and design rules. Herein, a translational framework engineered to accelerate the deployment of microfabricated interfaces for translational research is proposed and applied to the soft neurotechnology called electronic dura mater, e‐dura. Anatomy, implant function, and surgical procedure guide the system design. A high‐yield, silicone‐on‐silicon wafer process is developed to ensure reproducible characteristics of the electrodes. A biomimetic multimodal platform that replicates surgical insertion in an anatomy‐based model applies physiological movement, emulates therapeutic use of the electrodes, and enables advanced validation and rapid optimization in vitro of the implants. Functionality of scaled e‐dura is confirmed in nonhuman primates, where epidural neuromodulation of the spinal cord activates selective groups of muscles in the upper limbs with unmet precision. Performance stability is controlled over 6 weeks in vivo. The synergistic steps of design, fabrication, and biomimetic in vitro validation and in vivo evaluation in translational animal models are of general applicability and answer needs in multiple bioelectronic designs and medical technologies.

2020

Simultaneous decoding of cardiovascular and respiratory functional changes from pig intraneural vagus nerve signals

Silvestro Micera, Simone Romeni, Ivo Strauss

Objective. Bioelectronic medicine is opening new perspectives for the treatment of some major chronic diseases through the physical modulation of autonomic nervous system activity. Being the main peripheral route for electrical signals between central nervous system and visceral organs, the vagus nerve (VN) is one of the most promising targets. Closed-loop VN stimulation (VNS) would be crucial to increase effectiveness of this approach. Therefore, the extrapolation of useful physiological information from VN electrical activity would represent an invaluable source for single-target applications. Here, we present an advanced decoding algorithm novel to VN studies and properly detecting different functional changes from VN signals. Approach. VN signals were recorded using intraneural electrodes in anaesthetized pigs during cardiovascular and respiratory challenges mimicking increases in arterial blood pressure, tidal volume and respiratory rate. We developed a decoding algorithm that combines discrete wavelet transformation, principal component analysis, and ensemble learning made of classification trees. Main results. The new decoding algorithm robustly achieved high accuracy levels in identifying different functional changes and discriminating among them. Interestingly our findings suggest that electrodes positioning plays an important role on decoding performances. We also introduced a new index for the characterization of recording and decoding performance of neural interfaces. Finally, by combining an anatomically validated hybrid neural model and discrimination analysis, we provided new evidence suggesting a functional topographical organization of VN fascicles. Significance. This study represents an important step towards the comprehension of VN signaling, paving the way for the development of effective closed-loop VNS systems.

IOP PUBLISHING LTD2021

Simultaneous decoding of cardiovascular and respiratory functional changes from pig intraneural vagus nerve signals

Silvestro Micera, Simone Romeni, Ivo Strauss

IOP PUBLISHING LTD2021