Neurostimulation Devices for the Treatment of Neurologic Disorders

Abstract

Rapid advancements in neurostimulation technologies are providing relief to an unprecedented number of patients affected by debilitating neurologic and psychiatric disorders. Neurostimulation therapies include invasive and noninvasive approaches that involve the application of electrical stimulation to drive neural function within a circuit. This review focuses on established invasive electrical stimulation systems used clinically to induce therapeutic neuromodulation of dysfunctional neural circuitry. These implantable neurostimulation systems target specific deep subcortical, cortical, spinal, cranial, and peripheral nerve structures to modulate neuronal activity, providing therapeutic effects for a myriad of neuropsychiatric disorders. Recent advances in neurotechnologies and neuroimaging, along with an increased understanding of neurocircuitry, are factors contributing to the rapid rise in the use of neurostimulation therapies to treat an increasingly wide range of neurologic and psychiatric disorders. Electrical stimulation technologies are evolving after remaining fairly stagnant for the past 30 years, moving toward potential closed-loop therapeutic control systems with the ability to deliver stimulation with higher spatial resolution to provide continuous customized neuromodulation for optimal clinical outcomes. Even so, there is still much to be learned about disease pathogenesis of these neurodegenerative and psychiatric disorders and the latent mechanisms of neurostimulation that provide therapeutic relief. This review provides an overview of the increasingly common stimulation systems, their clinical indications, and enabling technologies.

An Acute Randomized Controlled Trial of Noninvasive Peripheral Nerve Stimulation in Essential Tremor

“…Further, due to the immediate therapeutic effect of stimulation, which is unlike other available pharmacologic interventions, kinematic measurements may provide insight into the effect of stimulation on tremor amplitude over time. This therapeutic approach was inspired by the observation that peripheral stimulation evokes central activity in brain regions such as the VIM, a target that when effectively stimulated with DBS can improve tremor (18). While the success of the patterned peripheral nerve stimulation tested here is consistent with this hypothesis, other potential mechanisms are possible, including circuitry modulated in previous studies demonstrating tremor reduction by manipulation of sensory input, including with topical anesthesia, cooling, vibration, and electrical stimulation (37)(38)(39)(40).…”

A novel re-attachable stereotactic frame for MRI-guided neuronavigation and its validation in a large animal and human cadaver model

“…Over the past decade, DBS therapy has emerged as the standard FDA-approved treatment option to treat medically-refractory movement and mood disruptions associated with Parkinson’s disease, essential tremor, dystonia, and obsessive-compulsive disorder (Edwards et al 2017). Furthermore, DBS therapy is under investigation for other neurologic and psychiatric disorders, including chronic pain, Tourette’s syndrome, Alzheimer’s disease, treatment-resistant depression, and addiction (Edwards et al 2017). Even so, although an unprecedented number of people have undergone DBS surgery, it remains vastly underutilized compared to the population of patients who would greatly benefit from DBS therapy (Shen 2014).…”

“…Each subject was intubated, and sedation was maintained with isoflurane (1%–3%) throughout the surgical procedure. The MRI-guided surgical approach was much like previously described clinical (Edwards et al 2017) and animal (Knight et al 2013) DBS procedures that used frame-based stereotactic systems. However, our stereotactic frame system differed by requiring precise orientation and spacing of skull anchor screws to preserve the spatial accuracy of the stereotactic system throughout the procedure.…”

Graded recruitment of pupil-linked neuromodulation by parametric stimulation of the vagus nerve

“…For over 30 years since then, VNS has been in wide use as an epilepsy treatment . In addition, VNS is currently explored in other brain disorders, such as major depression, anxiety, autism, tinnitus, and Alzheimer's disease (De Ridder et al, 2014;Edwards et al, 2017;Engineer et al, 2017;Fang et al, 2016;George and Aston-Jones, 2010;George et al, 2000;George et al, 2008;Nahas et al, 2005;Rush et al, 2005;Sjögren et al, 2002). Despite its wide and growing use, the mechanisms by which VNS exerts its clinical benefits are still largely unknown.…”

“…As a result, VNS settings are typically adjusted to "the highest 'comfortable' setting" based on patient feedback, an approach that likely contributes to variability in efficacy and impedes principled innovation Qing et al, 2018). Non-invasive biosensor(s), that could track the brain's response to VNS, would allow more systematic optimization of treatment in each patient, and potentially open up avenues for closed-loop, adaptive stimulation strategies that respond in real time to changes in the brain (Edwards et al, 2017;George and Aston-Jones, 2010).…”