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

Abstract

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.

Decoding Vagus-Nerve Activity with Carbon Nanotube Sensors in Freely Moving Rodents

“…Therefore, abnormal vagus-nerve activity has been linked to many chronic diseases, such as epilepsy, diabetes, hypertension, and cancer [ 1 , 2 , 3 , 4 , 5 ]. Vagus-nerve stimulation has been used to treat a wide variety of diseases [ 6 ], most successfully implemented for the treatment of epilepsy [ 7 ], even while the mechanisms are not well understood and direct recordings of vagal activity associated with disease are not available [ 8 ]. The majority of vagal afferent fibers come from the gut [ 9 , 10 ], and abnormal vagal activity has been clearly implicated in eating and metabolic disorders [ 11 , 12 , 13 , 14 , 15 ].…”

Closed-Loop Vagus Nerve Stimulation for the Treatment of Cardiovascular Diseases: State of the Art and Future Directions

“…While technology advances at a quick pace, neuromodulation’s ultimate potential can be realized when the relationship between nerve activity and physiological function is thoroughly known ( 4 , 6 ), thus allowing translation of biological information into appropriate engineering specifications ( 16 , 132 ). The knowledge gap of vagal physiology, functional anatomy and neuromodulation mechanisms inevitably also affects the selectivity of neural interfaces and of neuromodulation protocols ( 133 ). First of all, most VNS systems lack functional selectivity, that is stimulation of distinct functional classes of fibers, and are far from mimicking patterns of action potential occurring in healthy nerve fibers ( 32 , 133 ).…”

“…The knowledge gap of vagal physiology, functional anatomy and neuromodulation mechanisms inevitably also affects the selectivity of neural interfaces and of neuromodulation protocols ( 133 ). First of all, most VNS systems lack functional selectivity, that is stimulation of distinct functional classes of fibers, and are far from mimicking patterns of action potential occurring in healthy nerve fibers ( 32 , 133 ). Secondly, most VNS systems lack spatial selectivity, that is selective modulation of fibers in the specific anatomical territory innervated by a given fascicle ( 32 ).…”

A modular strategy for next-generation upper-limb sensory-motor neuroprostheses

“…Moreover, in this way, it could be possible to achieve more-selective muscular recruitment and neural blocking, which is very important for several applications. 107 ll Please cite this article in press as: Shokur et al, A modular strategy for next-generation upper-limb sensory-motor neuroprostheses, Med (2021), https://doi.org/10.1016/j.medj.2021.05.002…”