Flexible Peripheral Nerve Interfacing Electrode for Joint Position Control in Closed-Loop Neuromuscular Stimulation.

Addressing peripheral nerve disorders with electronic medicine poses significant challenges, especially in replicating the dynamic mechanical properties of nerves and understanding their functionality. In the field of electronic medicine, it is crucial to design a system that thoroughly understands the functions of the nervous system and ensures a stable interface with nervous tissue, facilitating autonomous neural adaptation. Herein, we present a novel neural interface platform that modulates the peripheral nervous system using flexible nerve electrodes and advanced neuromodulation techniques.

Acrylated adhesive proteinic microneedle patch for local drug delivery and stable device implantation.

Microneedle patches have been developed as favorable platforms for delivery systems, such as the locoregional application of therapeutic drugs, and implantation systems, such as electronic devices on visceral tissue surfaces. However, the challenge lies in finding materials that can achieve both biocompatibility and stable fixation on the target tissue. To address this issue, utilizing a biocompatible adhesive biomaterial allows the flat part of the patch to adhere as well, enabling double-sided adhesion for greater versatility.

A Customizable Proteinic Bioadhesive Patch with Water-Switchable Underwater Adhesiveness, Adjustable Biodegradability, and Modifiable Stretchability for Healing Diverse Internal Wounds.

Customizable bioadhesives for individual organ requirements, including tissue type and motion, are essential, especially given the rise in implantable medical device applications demanding adequate underwater adhesion. While synthetic bioadhesives are widely used, their toxicity upon degradation shifts focus to biocompatible natural biomaterials. However, enhancing the adhesive strengths of these biomaterials presents ongoing challenges while accommodating the unique properties of specific organs.

Electroconductive, Adhesive, Non-Swelling, and Viscoelastic Hydrogels for Bioelectronics.

As a new class of materials, implantable flexible electrical conductors have recently been developed and applied to bioelectronics. An ideal electrical conductor requires high conductivity, tissue-like mechanical properties, low toxicity, reliable adhesion to biological tissues, and the ability to maintain its shape in wet physiological environments. Despite significant advances, electrical conductors that satisfy all these requirements are insufficient.

Durable and Fatigue-Resistant Soft Peripheral Neuroprosthetics for In Vivo Bidirectional Signaling.

Soft neuroprosthetics that monitor signals from sensory neurons and deliver motor information can potentially replace damaged nerves. However, achieving long-term stability of devices interfacing peripheral nerves is challenging, since dynamic mechanical deformations in peripheral nerves cause material degradation in devices. Here, a durable and fatigue-resistant soft neuroprosthetic device is reported for bidirectional signaling on peripheral nerves.

Hemodynamic correlation imaging of the mouse brain for application in unilateral neurodegenerative diseases.

We developed a single-camera two-channel hemodynamic imaging system that uses near-infrared light to monitor the mouse brain in vivo with an exposed, un-thinned, and intact skull to explore the effect of Parkinson's disease on the resting state functional connectivity of the brain. To demonstrate our system's ability to monitor cerebral hemodynamics, we first performed direct electrical stimulation of an anesthetized healthy mouse brain and detected hemodynamic changes localized to the stimulated area. Subsequently, we developed a unilaterally lesioned 6-hydroxydopamine (hemi-parkinsonian) mouse model and detected the differences in functional connectivity between the normal and hemi-parkinsonian mouse brains by comparing the hemispheric hemodynamic correlations during the resting state.

Compact Neural Interface Using a Single Multichannel Cuff Electrode for a Functional Neuromuscular Stimulation System.

Cuff electrodes have been introduced into functional neuromuscular stimulation systems to either obtain neural signals or elicit limb movements. Multiple electrodes must be implanted to construct a feedback control loop, including one electrode for acquisition and another for stimulation. Existing approaches require too much space inside the body and a complicated surgical procedure.

Compact Optical Nerve Cuff Electrode for Simultaneous Neural Activity Monitoring and Optogenetic Stimulation of Peripheral Nerves.

Optogenetic stimulation of the peripheral nervous system is a novel approach to motor control, somatosensory transduction, and pain processing. Various optical stimulation tools have been developed for optogenetic stimulation using optical fibers and light-emitting diodes positioned on the peripheral nerve. However, these tools require additional sensors to monitor the limb or muscle status.

Graded 6-OHDA-induced dopamine depletion in the nigrostriatal pathway evokes progressive pathological neuronal activities in the subthalamic nucleus of a hemi-parkinsonian mouse.

Recent studies have established methods for establishing a rodent model that mimics progressive stages of human Parkinson's disease (PD), via injection of graded doses of 6-hydroxydopamine (6-OHDA) into regions within the nigrostriatal pathway. However, the electrophysiological characteristics of the subthalamic nucleus (STN) in this model have not been fully elucidated in this model. This study aimed to investigate changes in the neuronal activity of the STN in a graded mouse model of PD.

Localization of ultrasound waveform for low intensity ultrasound-induced neuromodulation in a mouse model.

A collimator design was investigated to localize ultrasound stimulation using a flat ultrasound transducer for ultrasound-induced neuromodulation in a mouse model. In brain stimulation, the specific location of stimulation must be specified, as the region responsible for motor or sensory function is clustered in a narrow brain area. To localize ultrasound stimulation, three types of collimator design were simulated to determine the optimal collimator design.

Differential heart rate variability and physiological responses associated with accumulated short- and long-term stress in rodents.

In this study, we tested the hypothesis that chronic stress has cumulative effects over time on heart rate variability (HRV) and physiological responses in a rodent model of chronic mild stress. Rats were exposed to either short-term (2weeks) or long-term (4weeks) stress, followed by a 1-week recovery period. Controls were normally housed rats that did not undergo the stress procedure.

Ankle-Angle Estimation from Blind Source Separated Afferent Activity in the Sciatic Nerve for Closed-Loop Functional Neuromuscular Stimulation System.

Cuff electrode recording has been proposed as a solution to obtain robust feedback signals for closed-loop controlled functional neuromuscular stimulation (FNS) systems. However, single-channel cuff electrode recording requires several electrodes to obtain the feedback signal related to each muscle. In this study, we propose an ankle-angle estimation method in which recording is conducted from the proximal nerve trunk with a multichannel cuff electrode to minimize cuff electrode usage.

Characteristics of the neuronal firing patterns in the subthalamic nucleus with graded dopaminergic cell loss in the nigrostriatal pathway.

The aim of this study was to evaluate the neuronal firing changes in the subthalamic nucleus (STN) in a graded mouse model of Parkinson's disease. Unilateral graded dopaminergic cell loss in the substantia nigra pars compacta was achieved by injecting different concentrations of 6-hydroxydopamine (6-OHDA) in the right medial forebrain bundle. Electrophysiological analysis of neuronal firing patterns in the STN revealed an increased firing rate, burst index, and interspike interval coefficient of variation in groups treated with higher 6-OHDA concentrations.

An implantable wireless optogenetic stimulation system for peripheral nerve control.

An implantable wireless optogenetic stimulation system with an LED-based optical stimulation cuff electrode was developed for peripheral nerve control. The proposed system consisted of a battery-powered optical cuff electrode, optical stimulation controller, and wireless communication system. The optical cuff electrode had a polydimethylsiloxane (PDMS) structure was designed to illuminate the entire sciatic nerve.

A time-course study of behavioral and electrophysiological characteristics in a mouse model of different stages of Parkinson's disease using 6-hydroxydopamine.

Parkinson's disease (PD) is characterized by abnormal motor symptoms and increased neuronal activity in the subthalamic nucleus (STN) as the disease progresses. We investigated the behavioral and electrophysiological characteristics in a mouse model mimicking the progressive stages of human PD (early, moderate, and advanced) by injecting 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle (MFB) at three different concentrations (2, 4, and 6 μg/2 μl). Significant changes in motor symptoms were demonstrated between groups in association with relative TH-positive cell loss in the substantia nigra pars compacta (SNc).

An implantable wireless system for muscle afferent recording from the sciatic nerve during functional electrical stimulation.

An implantable wireless system was developed for recording muscle afferent activity and stimulating peripheral nerves with cuff electrodes. The proposed system was fabricated into the nerve cuff electrode, neural amplifier, neural stimulator, and wireless communication system with battery power. The nerve cuff electrode and neural amplifier were designed to improve the signal-to-interference ratio and signal-to-noise ratio.

Feedback control of electrode offset voltage during functional electrical stimulation.

Control of the electrode offset voltage is an important issue related to the processes of functional electrical stimulation because excess charge accumulation over time damages both the tissue and the electrodes. This paper proposes a new feedback control scheme to regulate the electrode offset voltage to a predetermined reference value. The electrode offset voltage was continuously monitored using a sample-and-hold (S/H) circuit during stimulation and non-stimulation periods.

Gait phase detection from sciatic nerve recordings in functional electrical stimulation systems for foot drop correction.

Cutaneous afferent activities recorded by a nerve cuff electrode have been used to detect the stance phase in a functional electrical stimulation system for foot drop correction. However, the implantation procedure was difficult, as the cuff electrode had to be located on the distal branches of a multi-fascicular nerve to exclude muscle afferent and efferent activities. This paper proposes a new gait phase detection scheme that can be applied to a proximal nerve root that includes cutaneous afferent fibers as well as muscle afferent and efferent fibers.

Improvement of signal-to-interference ratio and signal-to-noise ratio in nerve cuff electrode systems.

Cuff electrodes are effective for chronic electroneurogram (ENG) recording while minimizing nerve damage. However, the ENG signals are usually contaminated by electromyogram (EMG) activity from the surrounding muscles, stimulus artifacts produced by the electrical stimulation and noise generated in the first stage of the neural signal amplifier. This paper proposed a new cuff electrode to reduce the interference from EMG signals and stimulus artifacts.

Spontaneous synchronized burst firing of subthalamic nucleus neurons in rat brain slices measured on multi-electrode arrays.

The current study presents an organotypic rat midbrain slice culture that served as a consistent and informative framework, where the STN neurons and their interconnectivity were closely examined with respect to electrophysiological and pharmacological properties. From multi-electrode array recordings, it was found that the majority of STN neurons spontaneously fired in bursts rather than tonically under control conditions, and the neural activity between pairs of burst-firing STN neurons was tightly correlated. This spontaneous synchronized burst firing was also affected by a glutamate receptor antagonist, yet unaffected by a GABA receptor antagonist.