Using Compound Neural Action Potentials for Functional Validation of a High-Density Intraneural Interface: A Preliminary Study.

Compound nerve action potentials (CNAPs) were used as a metric to assess the stimulation performance of a novel high-density, transverse, intrafascicular electrode in rat models. We show characteristic CNAPs recorded from distally implanted cuff electrodes. Evaluation of the CNAPs as a function of stimulus current and calculation of recruitment plots were used to obtain a qualitative approximation of the neural interface's placement and orientation inside the nerve.

Subdiaphragmatic vagal nerve stimulation attenuates the development of hypertension and alters nucleus of the solitary tract transcriptional networks in the spontaneously hypertensive rat.

Augmented vagal signaling may be therapeutic in hypertension. Most studies to date have used stimulation of the cervical vagal branches. Here, we investigated the effects of chronic intermittent electric stimulation of the ventral subdiaphragmatic vagal nerve branch (sdVNS) on long-term blood pressure, immune markers, and gut microbiota in the spontaneously hypertensive rat (SHR), a rodent model of hypertension characterized by vagal dysfunction, gut dysbiosis, and low-grade inflammation.

High frequency alternating current neurostimulation decreases nocifensive behavior in a disc herniation model of lumbar radiculopathy.

Background: The purpose of this study was to evaluate if kilohertz frequency alternating current (KHFAC) stimulation of peripheral nerve could serve as a treatment for lumbar radiculopathy. Prior work shows that KHFAC stimulation can treat sciatica resulting from chronic sciatic nerve constriction. Here, we evaluate if KHFAC stimulation is also beneficial in a more physiologic model of low back pain which mimics nucleus pulposus (NP) impingement of a lumbar dorsal root ganglion (DRG).

The effects of targeted vagus nerve stimulation on glucose homeostasis in STZ-induced diabetic rodents.

During type 1 diabetes, an autoimmune attack destroys pancreatic β-cells leading to the inability to maintain glucose homeostasis. These β-cells are neuroresponsive endocrine cells which normally secrete insulin partially in response to input from the vagus nerve. This neural pathway can be utilized as a point of therapeutic intervention by delivering exogenous stimulation to drive increased insulin secretion.

Layer-dependent stability of intracortical recordings and neuronal cell loss.

Intracortical recordings can be used to voluntarily control external devices brain-machine interfaces (BMI). Multiple factors, including the foreign body response (FBR), limit the stability of these neural signals over time. Current clinically approved devices consist of multi-electrode arrays with a single electrode site at the tip of each shank, confining the recording interface to a single layer of the cortex.

Neuromodulation as a Potential Disease-Modifying Therapy for Osteoarthritis.

Purpose Of Review: The following review discusses the therapeutic potential of targeting the autonomic nervous system (ANS) for osteoarthritis (OA) treatment and encourages the field to consider the candidacy of bioelectronic medicine as a novel OA treatment strategy.

Recent Findings: The study of OA pathogenesis has focused on changes occurring at the joint level. As such, treatments for OA have been aimed at the local joint environment, intending to resolve local inflammation and decrease pain.

Examining thefunctionality of the magnetically aligned regenerative tissue-engineered electronic nerve interface (MARTEENI).

. Although neural-enabled prostheses have been used to restore some lost functionality in clinical trials, they have faced difficulty in achieving high degree of freedom, natural use compared to healthy limbs. This study investigated thefunctionality of a flexible and scalable regenerative peripheral-nerve interface suspended within a microchannel-embedded, tissue-engineered hydrogel (the magnetically aligned regenerative tissue-engineered electronic nerve interface (MARTEENI)) as a potential approach to improving current issues in peripheral nerve interfaces.

Reducing Behavioral Detection Thresholds per Electrode Synchronous, Spatially-Dependent Intracortical Microstimulation.

Intracortical microstimulation (ICMS) has shown promise in restoring quality of life to patients suffering from paralysis, specifically when used in the primary somatosensory cortex (S1). However, these benefits can be hampered by long-term degradation of electrode performance due to the brain's foreign body response. Advances in microfabrication techniques have allowed for the development of neuroprostheses with subcellular electrodes, which are characterized by greater versatility and a less detrimental immune response during chronic use.

The Long-Term Stability of Intracortical Microstimulation and the Foreign Body Response Are Layer Dependent.

Intracortical microstimulation (ICMS) of the somatosensory cortex (S1) can restore sensory function in patients with paralysis. Studies assessing the stability of ICMS have reported heterogeneous responses across electrodes and over time, potentially hindering the implementation and translatability of these technologies. The foreign body response (FBR) and the encapsulating glial scar have been associated with a decay in chronic performance of implanted electrodes.

Closed-Loop, Cervical, Epidural Stimulation Elicits Respiratory Neuroplasticity after Spinal Cord Injury in Freely Behaving Rats.

Over half of all spinal cord injuries (SCIs) are cervical, which can lead to paralysis and respiratory compromise, causing significant morbidity and mortality. Effective treatments to restore breathing after severe upper cervical injury are lacking; thus, it is imperative to develop therapies to address this. Epidural stimulation has successfully restored motor function after SCI for stepping, standing, reaching, grasping, and postural control.

Development of a magnetically aligned regenerative tissue-engineered electronic nerve interface for peripheral nerve applications.

Peripheral nerve injuries can be debilitating to motor and sensory function, with severe cases often resulting in complete limb amputation. Over the past two decades, prosthetic limb technology has rapidly advanced to provide users with crude motor control of up to 20° of freedom; however, the nerve-interfacing technology required to provide high movement selectivity has not progressed at the same rate. The work presented here focuses on the development of a magnetically aligned regenerative tissue-engineered electronic nerve interface (MARTEENI) that combines polyimide "threads" encapsulated within a magnetically aligned hydrogel scaffold.

The Role of Electrode-Site Placement in the Long-Term Stability of Intracortical Microstimulation.

Intracortical microelectrodes are neuroprosthetic devices used in brain-machine interfaces to both record and stimulate neural activity in the brain. These technologies have been improved by advances in microfabrication, which have led to the creation of subcellular and high-density microelectrodes. The greater number of independent stimulation channels in these devices allows for improved neuromodulation selectivity, compared to single-site microelectrodes.

Engineering the Multi-Enzymatic Activity of Cerium Oxide Nanoparticle Coatings for the Antioxidant Protection of Implants.

Imbalance of oxidants is a universal contributor to the failure of implanted devices and tissues. A sustained oxidative environment leads to cytotoxicity, prolonged inflammation, and ultimately host rejection of implanted devices/grafts. The incorporation of antioxidant materials can inhibit this redox/inflammatory cycle and enhance implant efficacy.

Acute vagus nerve stimulation enhances reversal learning in rats.

Cognitive flexibility is a prefrontal cortex-dependent neurocognitive process that enables behavioral adaptation in response to changes in environmental contingencies. Electrical vagus nerve stimulation (VNS) enhances several forms of learning and neuroplasticity, but its effects on cognitive flexibility have not been evaluated. In the current study, a within-subjects design was used to assess the effects of VNS on performance in a novel visual discrimination reversal learning task conducted in touchscreen operant chambers.

Electrical epidural stimulation of the cervical spinal cord: implications for spinal respiratory neuroplasticity after spinal cord injury.

Traumatic cervical spinal cord injury (cSCI) can lead to damage of bulbospinal pathways to the respiratory motor nuclei and consequent life-threatening respiratory insufficiency due to respiratory muscle paralysis/paresis. Reports of electrical epidural stimulation (EES) of the lumbosacral spinal cord to enable locomotor function after SCI are encouraging, with some evidence of facilitating neural plasticity. Here, we detail the development and success of EES in recovering locomotor function, with consideration of stimulation parameters and safety measures to develop effective EES protocols.

Proceedings of the Eighth Annual Deep Brain Stimulation Think Tank: Advances in Optogenetics, Ethical Issues Affecting DBS Research, Neuromodulatory Approaches for Depression, Adaptive Neurostimulation, and Emerging DBS Technologies.

We estimate that 208,000 deep brain stimulation (DBS) devices have been implanted to address neurological and neuropsychiatric disorders worldwide. DBS Think Tank presenters pooled data and determined that DBS expanded in its scope and has been applied to multiple brain disorders in an effort to modulate neural circuitry. The DBS Think Tank was founded in 2012 providing a space where clinicians, engineers, researchers from industry and academia discuss current and emerging DBS technologies and logistical and ethical issues facing the field.

A multi-channel peripheral nerve stimulator with integrate-and-fire encoding.

Activation of peripheral nervous system (PNS) fibres to produce variable tactile and proprioceptive sensations in advanced bidirectional prosthetic limbs relies on neural stimulators with high spatial selectivity, dynamic range and resolution. A multi-channel application-specific integrated circuit (ASIC) is developed for PNS fibre activation using a wide dynamic range (10 nA-5 mA), high-resolution (30 nA step, 100 ns pulse accuracy) current stimulator, dissipating 0.73-2.

Layer-specific parameters of intracortical microstimulation of the somatosensory cortex.

. Intracortical microstimulation of the primary somatosensory cortex (S1) has shown great progress in restoring touch sensations to patients with paralysis. Stimulation parameters such as amplitude, phase duration, and frequency can influence the quality of the evoked percept as well as the amount of charge necessary to elicit a response.

Restoration of breathing after opioid overdose and spinal cord injury using temporal interference stimulation.

Respiratory insufficiency is a leading cause of death due to drug overdose or neuromuscular disease. We hypothesized that a stimulation paradigm using temporal interference (TI) could restore breathing in such conditions. Following opioid overdose in rats, two high frequency (5000 Hz and 5001 Hz), low amplitude waveforms delivered via intramuscular wires in the neck immediately activated the diaphragm and restored ventilation in phase with waveform offset (1 Hz or 60 breaths/min).

Designing a bioelectronic treatment for Type 1 diabetes: targeted parasympathetic modulation of insulin secretion.

The pancreas is a visceral organ with exocrine functions for digestion and endocrine functions for maintenance of blood glucose homeostasis. In pancreatic diseases such as Type 1 diabetes, islets of the endocrine pancreas become dysfunctional and normal regulation of blood glucose concentration ceases. In healthy individuals, parasympathetic signaling to islets via the vagus nerve, triggers release of insulin from pancreatic β-cells and glucagon from α-cells.

Partial high frequency nerve block decreases neuropathic signaling following chronic sciatic nerve constriction injury.

High frequency (HF) block can quickly and reversibly stop nerve conduction. We hypothesized HF block at the sciatic nerve would minimize nociception by preventing neuropathic signals from reaching the central nervous system.Lewis rats were implanted with a constriction cuff and a distal cuff electrode around their right sciatic nerve.

Second Harmonic Generation Imaging of Collagen in Chronically Implantable Electrodes in Brain Tissue.

Advances in neural engineering have brought about a number of implantable devices for improved brain stimulation and recording. Unfortunately, many of these micro-implants have not been adopted due to issues of signal loss, deterioration, and host response to the device. While glial scar characterization is critical to better understand the mechanisms that affect device functionality or tissue viability, analysis is frequently hindered by immunohistochemical tissue processing methods that result in device shattering and tissue tearing artifacts.

Targeted Vagus Nerve Stimulation does not Disrupt Cardiac Function in the Diabetic Rat.

In this study, we acutely identified a target branch of the vagus nerve known as the pancreatic branch of the vagus nerve, which exclusively innervates the pancreas by applying electrical stimulus to the known cervical vagus nerve and observing compound neural action potentials at the target nerve. In a set of chronically implanted rats, the target nerve was again cuffed using an electrode and also implanted with a continuous glucose monitor. A model of type 1 diabetes (T1D) was chemically induced and hyperglycemic state confirmed.