When Spinal Neuromodulation Meets Sensorimotor Rehabilitation: Lessons Learned From Animal Models to Regain Manual Dexterity After a Spinal Cord Injury

Electrical neuromodulation has strongly hit the foundations of spinal cord injury and repair. Clinical and experimental studies have demonstrated the ability to neuromodulate and engage spinal cord circuits to recover volitional motor functions lost after the injury. Although the science and technology behind electrical neuromodulation has attracted much of the attention, it cannot be obviated that electrical stimulation must be applied concomitantly to sensorimotor rehabilitation, and one would be very difficult to understand without the other, as both need to be finely tuned to efficiently execute movements. The present review explores the difficulties faced by experimental and clinical neuroscientists when attempting to neuromodulate and rehabilitate manual dexterity in spinal cord injured subjects. From a translational point of view, we will describe the major rehabilitation interventions employed in animal research to promote recovery of forelimb motor function. On the other hand, we will outline some of the state-of-the-art findings when applying electrical neuromodulation to the spinal cord in animal models and human patients, highlighting how evidences from lumbar stimulation are paving the path to cervical neuromodulation.

Transdermal Electrical Neuromodulation for Anxiety and Sleep Problems in High-Functioning Autism Spectrum Disorder: Feasibility and Preliminary Findings

Background: Autism spectrum disorder (ASD) is associated with anxiety and sleep problems. We investigated transdermal electrical neuromodulation (TEN) of the cervical nerves in the neck as a safe, effective, comfortable and non-pharmacological therapy for decreasing anxiety and enhancing sleep quality in ASD. Methods: In this blinded, sham-controlled study, seven adolescents and young adults with high-functioning ASD underwent five consecutive treatment days, one day of the sham followed by four days of subthreshold TEN for 20 min. Anxiety-provoking cognitive tasks were performed after the sham/TEN. Measures of autonomic nervous system activity, including saliva α-amylase and cortisol, electrodermal activity, and heart rate variability, were collected from six participants. Results: Self-rated and caretaker-rated measures of anxiety were significantly improved with TEN treatment as compared to the sham, with effect sizes ranging from medium to large depending on the rating scale. Sleep scores from caretaker questionnaires also improved, but not significantly. Performance on two of the three anxiety-provoking cognitive tasks and heart rate variability significantly improved with TEN stimulation as compared to the sham. Four of the seven (57%) participants were responders, defined as a ≥ 30% improvement in self-reported anxiety. Salivary α-amylase decreased with more TEN sessions and decreased from the beginning to the end of the session on TEN days for responders. TEN was well-tolerated without significant adverse events. Conclusions: This study provides preliminary evidence that TEN is well-tolerated in individuals with ASD and can improve anxiety.

Restoring Sensorimotor Function Through Neuromodulation After Spinal Cord Injury: Progress and Remaining Challenges

Spinal cord injury (SCI) is a major disability that results in motor and sensory impairment and extensive complications for the affected individuals which not only affect the quality of life of the patients but also result in a heavy burden for their families and the health care system. Although there are few clinically effective treatments for SCI, research over the past few decades has resulted in several novel treatment strategies which are related to neuromodulation. Neuromodulation—the use of neuromodulators, electrical stimulation or optogenetics to modulate neuronal activity—can substantially promote the recovery of sensorimotor function after SCI. Recent studies have shown that neuromodulation, in combination with other technologies, can allow paralyzed patients to carry out intentional, controlled movement, and promote sensory recovery. Although such treatments hold promise for completely overcoming SCI, the mechanisms by which neuromodulation has this effect have been difficult to determine. Here we review recent progress relative to electrical neuromodulation and optogenetics neuromodulation. We also examine potential mechanisms by which these methods may restore sensorimotor function. We then highlight the strengths of these approaches and remaining challenges with respect to its application.

Nerivio® remote electrical neuromodulation for acute treatment of chronic migraine

Nerivio® (by Theranica Bio-Electronics Ltd, Tel Aviv, Israel) is a wireless, wearable, noninvasive, battery-operated, remote electrical neuromodulation device controlled by a smartphone application. It is US FDA authorized for the acute treatment of migraine with or without aura in people 12 years and older in the US, and European Conformity (CE) marked for the same indication in the EU. The American Headache Society Consensus Statement recommends Nerivio as a tier 2 treatment for migraines. This review summarizes a series of five independent clinical trials and two real-world evidence studies that established safety, tolerability and efficacy of Nerivio in treating migraine attacks. It further provides up-to-date practical information on device usability. Based on findings of this review, Nerivio offers a safe and effective nonpharmacological alternative for acute treatment in patients with chronic (and nonchronic) migraine.

Cervical transcutaneous vagal nerve stimulation (ctVNS) improves human cognitive performance under sleep deprivation stress

Fatigue is a pervasive public health and safety issue. Common fatigue countermeasures include caffeine or other chemical stimulants. These can be effective in limited circumstances but other non-pharmacological fatigue countermeasures such as non-invasive electrical neuromodulation have shown promise. It is reasonable to suspect that other types of non-invasive neuromodulation may be similarly effective or perhaps even superior. The objective of this research was to evaluate the efficacy of cervical transcutaneous vagal nerve stimulation (ctVNS) to mitigate the negative effects of fatigue on cognition and mood. Two groups (active or sham stimulation) of twenty participants in each group completed 34 h of sustained wakefulness. The ctVNS group performed significantly better on arousal, multi-tasking, and reported significantly lower fatigue ratings compared to sham for the duration of the study. CtVNS could be a powerful fatigue countermeasure tool that is easy to administer, long-lasting, and has fewer side-effects compared to common pharmacological interventions.