Constant Current Stimulation Research Articles

Design and Ex Vivo Experimental Validations of the CMOS 256-Pixel Photovoltaic-Powered Subretinal Prosthetic Chip With Auto-Adaptive Pixels for a Wide Image Illuminance Range.

To design and verify a CMOS 256-pixel photovoltaic-powered subretinal prosthetic chip with key advances over the state-of-the-art. The three key advances are: 1) automatic adaptation to changing background illuminance levels; 2) increase of injection charges with reduced crosstalk leakage charges, enhanced charge balance, and low process variations; 3) stable stimulation voltage to keep the safety of water window. The novel auto-adaptive pixel circuit is designed to realize the Michealis - Menten equation (MME) so that the automatic adaptation to changing background illuminance can be achieved. Both improved biphasic constant current stimulator (CCS) via bi-directional shared electrodes (BDSEs) with optimized stimulation pattern and improved constant current generator/ring oscillator are designed to achieve the above second advance on injection charges. The closed-loop charge pump is designed to achieve the third advance. The measured dynamic range of image illuminance is increased to 54.7 dB. The maximum stimulation charge is 8.89nC. The measured stimulation current mismatch is 1.7% and the measured residual charge is 0.150 nC. The measured variations of stimulation frequencies are from 26 Hz to 29.7 Hz. The results of ex vivo tests have shown that the proposed subretinal chip can evoke spiking responses of RGCs. The function of adaptation process to background illuminance has also been verified. Through both electrical measurement and ex vivo tests, the functions of designed subretinal chip have been validated successfully. It is shown that the proposed subretinal chip is a promising solution for subretinal prostheses.

Sputtered Ruthenium Oxide Neural Stimulation Electrodes.

We have investigated the charge-injection properties of sputtered ruthenium oxide (RuOx) coatings deposited on planar microelectrode arrays. Substantial charge was found to be available for injection within -0.6/0.6 V vs Ag|AgCl potential limits for the sputtered RuOx film. The charge-injection capacity increased further upon extending the potential limits to -0.7/0.7 V vs Ag|AgCl. No oxygen reduction, an unwanted side reaction, was observed during the pulsing of sputtered RuOx microelectrodes in phosphate buffered saline solution. Additionally, the RuOx coatings were found to be electrochemically stable for up to 1-billion-cycles of constant current stimulation pulsing at 8 nC/phase in model-ISF at 37° C.

Fast or Slow? A Comparison Between Two Transcranial Electrical Stimulation Techniques for Eliciting Motor-Evoked Potentials During Supratentorial Surgery.

During intraoperative neurophysiological monitoring of motor pathways, two types of transcranial electrical stimulation are available, i.e., constant-current and constant-voltage stimulation. Few previous studies, performed only during spinal surgery, analyzed and compared them during intraoperative neurophysiological monitoring. The aim of our study was to compare these two stimulation techniques for eliciting motor-evoked potentials during intraoperative neurophysiological monitoring in a group of patients affected by supratentorial lesions. Supratentorial lesions from 16 patients were retrospectively collected and analyzed. Motor-evoked potentials were performed only from transcranial electrical stimulation because the inability to place the subdural strip electrodes correctly did not permit to perform direct cortical stimulation. At the beginning of surgery, in each patient, motor-evoked potentials were monitored by using both "fast-charge" constant-voltage and "slow-charge" constant-current stimulation. Several neurophysiological parameters were collected and compared between the two stimulation techniques by means of statistical analysis. "Fast-charge" constant-voltage stimulation allowed statistically higher efficiency rates for eliciting motor-evoked potentials compared with "slow-charge" constant-current stimulation, both for upper and lower limbs. We also found that threshold and maximal charge as well as charge density were significantly lower during constant-voltage stimulation, thus lowering the potential tissue damage. "Fast-charge" constant-voltage transcranial electrical stimulation is feasible and safe during intraoperative neurophysiological monitoring for supratentorial surgery and may be preferable to "slow-charge" constant-current stimulation.

Design of a Bone-Guided Cochlear Implant Microsystem With Monopolar Biphasic Multiple Stimulations and Evoked Compound Action Potential Acquisition and Its In Vivo Verification

A CMOS bone-guided cochlear implant (BGCI) microsystem is proposed and verified. In the implanted System on Chip (SoC) of the proposed BGCI, the evoked compound action potential (ECAP) acquisition and electrode–tissue impedance measurement (EAEIM) circuit is integrated to measure both ECAP and electrode–tissue impedance for clinical diagnoses. Both positive-/negative-voltage charge pumps and monopolar biphasic constant-current stimulation (CCS) stimulator are designed on-chip to realize monopolar biphasic CCS or double-electrode multiple stimulations with a maximum stimulation current of 1.2 mA and a step of 10 <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\mu \text{A}$ </tex-math></inline-formula> . With the double-electrode multiple stimulations, the electric field can be shifted and localized under the stimulating electrode to stimulate the auditory nerves. The wireless bilateral data telemetry circuits with a full-wave active rectifier and the pulsed load-shift keying (PLSK) modulators/demodulators are designed for power and data transmission. <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">In vivo</i> animal tests on guinea pigs have shown that the Wave III of electrically evoked auditory brainstem responses (EABRs) can be evoked successfully by electrical stimulation. Moreover, the decreasing latency gradient of evoked Wave III has been measured under the double-electrode multiple stimulations where the location of peak electric field can be shifted to the stimulating electrode in the apical site to stimulate the auditory nerves. Thus, the desired frequency resolution and spatial specificity of stimulation can be achieved. Both electrical measurement and <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">in vivo</i> animal tests have verified that the proposed BGCI microsystem is a feasible solution to eliminate the symptoms for patients with high-frequency hearing loss.

Modeling the Impact of Electrode/Tissue Geometry on Electrical Stimulation in Stereo-EEG.

Electrical stimulation through depth electrodes is used to map function and seizure onset during stereoelectroencephalography in patients undergoing evaluation for epilepsy surgery. Factors such as electrode design, location, and orientation are expected to impact effects of electrical stimulation. We developed a steady-state finite element model of brain tissue including five layers (skull through white matter) and an implanted electrode to explore the impact of electrode design and placement on the activation of brain tissue by electrical stimulation. We calculated electric potentials, current densities, and volume of tissue activated ( Volact ) in response to constant current bipolar stimulation. We modeled two depth electrode designs (3.5- and 4.43-mm intercontact spacing) and varied electrode location and orientation. The electrode with greater intercontact spacing produced 8% to 23% larger Volact (1% to 16% considering only gray matter). Vertical displacement of the electrodes by half intercontact space increased Volact for upward displacement (6% to 83% for all brain tissue or -5% to 96% gray matter only) and decreased Volact (1% to 16% or 24% to 49% gray matter only) for downward displacement. Rotating the electrode in the tissue by 30° to 60° with respect to the vertical axis increased Volact by 30% to 90% (20%-48% gray matter only). Location and orientation of depth electrodes with respect to surrounding brain tissue have a large impact on the amount of tissue activated during electrical stimulation mapping in stereoelectroencephalography. Electrode design has an impact, although modest for commonly used designs. Individualization of stimulation intensity at each location remains critical, especially for avoiding false-negative results.

From Bioelectronics to Nanobioelectronics: The Biomedical Electronics Translational Research Center [Highlights

Discusses the an evolving theraphy called electrical neuromodulation. This new therapy offers targeted delivery of constant voltage stimulation or constant current stimulation (CCS) to specific neurological sites to enable the alteration of nerve activities. It can influence nerves by releasing transmitters, such as dopamine, and other chemical messengers, including peptides, that can modulate the excitatory and inhibitory functions of neural circuits. The end effect is the normalization of a neural network function from its perturbed state. The presumed mechanisms of electrical neuromodulation could include a depolarizing blockade, the stochastic normalization of neural firing, an axonal blockade, the reduction of neural firing keratosis, and the suppression of neural network oscillations [1]. Although the exact mechanisms of electrical neuromodulation are not known, the procedure’s empirical effectiveness has led to numerous clinical applications.

The mite Varroa destructor lowers the stinging response threshold of honey bees (Apis mellifera)

The ecto-parasitic mite Varroa destructor is an extremely damaging biotic factor of honey bees (Apis mellifera) worldwide. The magnitude of the damage that V. destructor causes to the health of honey bees is well documented, but little is known about how it affects their behavior. For example, it is not known whether parasitism by V. destructor influences the bees’ defensive behavior, and since this behavior has evolutionary and practical implications, its study is of importance. In this research, we used a constant-current stimulator to expose worker bees to a 0.5 mA electric stimulus after being parasitized by Varroa mites to test the hypothesis that V. destructor parasitism affects the stinging response threshold of individual honey bees. Bees exposed to V. destructor parasitism stung significantly faster than control bees in each of three trials (p < 0.05) and thus, it is concluded that the irritation caused by V. destructor reduces the stinging response threshold of honey bees. The implications of these findings are discussed, as well as the need for further studies to understand how V. destructor affects neuronal processes in the honey bee to make them more defensive.

Arousal Promoting Effects of Basal Forebrain are Mediated through Prefrontal Cortex in Rat

Background We recently showed that cholinergic stimulation of prefrontal cortex (PFC), via local carbachol delivery, increased local acetylcholine (ACh) levels and restored wakefulness in sevoflurane-anesthetized rats.[1] PFC receives cholinergic projections from basal forebrain (BF), and activation of cholinergic BF neurons has been shown to promote behavioral arousal.[2] Increase in prefrontal ACh during carbachol-induced wake state reflects BF activation, but it is not known if BF acts via PFC to promote behavioral arousal. The objective of the current study is to test the hypothesis that PFC gates the arousal promoting effects of BF. Methods Under isoflurane anesthesia, Sprague Dawley rats (n=3) were implanted with bipolar wire electrodes (500um diameter) bilaterally into BF (Bregma: posterior 0.48mm, mediolateral 2.0mm, ventral 8.2mm), screw electrodes across the cortex to record electroencephalogram (EEG), and a bilateral guide cannula aimed at PFC (Bregma: anterior 3.0mm, mediolateral 0.5mm, ventral 4.0mm). Another group of Sprague Dawley rats (n=2) was implanted with the electrical stimulation electrodes into piriform cortex (Bregma: posterior 0.48mm, mediolateral 5.0mm, ventral 9.0mm), as a control anatomical site. All coordinates are as per the stereotaxic atlas by Paxinos and Watson.[3] After 7-10 days of post-surgical recovery, we conducted bilateral constant current electrical stimulation of BF (200Hz, 30s ON and 30s OFF - three cycles at 60uA and three cycles at 100uA) in sevoflurane-anesthetized rats (1.9-2.4%) with or without concurrent inactivation of PFC via local bilateral infusion of tetrodotoxin (156µM, 500nL). The same paradigm was used for electrical stimulation of piriform cortex. Results Electrical stimulation of BF in sevoflurane-anesthetized rats induced signs of behavioral arousal (whisker, orofacial and limb movements, and attempts at/regaining of the righting reflex), activated the EEG, and increased the heart (~13%) and respiration (~67%) rate. By contrast, electrical stimulation of BF in the presence of tetrodotoxin in PFC failed to induce behavioral arousal and EEG activation. Electrical stimulation of the control anatomical site (piriform cortex) in sevoflurane-anesthetized rat did not induce behavioral arousal. Conclusions These results suggest that the arousal promoting effects of BF are gated through PFC, potentially through a cholinergic circuit.

Tenderness of the Skin after Chemical Stimulation of Underlying Temporal and Thoracolumbar Fasciae Reveals Somatosensory Crosstalk between Superficial and Deep Tissues.

Musculoskeletal pain is often associated with pain referred to adjacent areas or skin. So far, no study has analyzed the somatosensory changes of the skin after the stimulation of different underlying fasciae. The current study aimed to investigate heterotopic somatosensory crosstalk between deep tissue (muscle or fascia) and superficial tissue (skin) using two established models of deep tissue pain (namely focal high frequency electrical stimulation (HFS) (100 pulses of constant current electrical stimulation at 10× detection threshold) or the injection of hypertonic saline in stimulus locations as verified using ultrasound). In a methodological pilot experiment in the TLF, different injection volumes of hypertonic saline (50–800 µL) revealed that small injection volumes were most suitable, as they elicited sufficient pain but avoided the complication of the numbing pinprick sensitivity encountered after the injection of a very large volume (800 µL), particularly following muscle injections. The testing of fascia at different body sites revealed that 100 µL of hypertonic saline in the temporal fascia and TLF elicited significant pinprick hyperalgesia in the overlying skin (–26.2% and –23.5% adjusted threshold reduction, p < 0.001 and p < 0.05, respectively), but not the trapezius fascia or iliotibial band. Notably, both estimates of hyperalgesia were significantly correlated (r = 0.61, p < 0.005). Comprehensive somatosensory testing (DFNS standard) revealed that no test parameter was changed significantly following electrical HFS. The experiments demonstrated that fascia stimulation at a sufficient stimulus intensity elicited significant across-tissue facilitation to pinprick stimulation (referred hyperalgesia), a hallmark sign of nociceptive central sensitization.

Cutaneous sensation of electrical stimulation waveforms

BackgroundSkin sensation is the primary factor limiting the intensity of transcranial electrical stimulation (tES). It is well established that different waveforms generate different sensations, yet transcranial stimulation has been limited to a relatively small number of prototypical waveforms. ObjectiveWe explore whether alternative stimulation waveforms could substantially reduce skin sensation and thus allow for stronger intensities in tES. MethodsWe systematically tested a range of waveforms in a series of 6 exploratory experiments stimulating human adults on the forearm and in one instance on the head. Subjects were asked to rate skin sensation level on a numerical scale from “none” to “extreme”. ResultsHigh frequency (>1 kHz) monophasic square wave stimulation was found to decrease in sensation with increasing duty cycle, baseline, and frequency, but the sensation was never lower than for constant current stimulation. For the purpose of injecting a net direct current (DC), a constant current is optimal. For stimulation with alternating current (AC), sensation decreased with increasing frequency, consistent with previous reports. Amplitude modulation did not reduce sensation below stimulation with constant AC amplitude, and biphasic square waveforms produced higher sensation levels than biphasic sinusoidal waveforms. Furthermore, for DC stimulation, sensation levels on the arm were similar to those reported on the head. ConclusionOur comparisons of various waveforms for monophasic and biphasic stimulation indicate that conventional DC and AC waveforms may provide the lowest skin sensations levels for transcutaneous electrical stimulation. These results are likely generalizable to tES applications.

Low-cost stimulation resistant electromyography

Surface Electromyography (sEMG) is the non-invasive measurement of skeletal muscle contraction bio-potentials. Measuring sEMG of a stimulated muscle can prove particularly difficult due to large scale and long lasting stimulation-induced artefacts: if an sEMG device does not account for such artefacts, its measurements can be swamped and components damaged. sEMG has been used in a wide range of clinical and biomedical fields, providing measures such as muscular fatigue and subject intent. The recording of sEMG can prove difficult due to signal contamination such as movement artefact and mains interference.There are very few commercial sEMG devices that contain protection against large stimulation voltages or measures to reduce artefact transient times. Furthermore, most commercial or research level designs are not open source; these designs are effectively an inflexible black box to researchers and developers.This research presents the design, test and validation of an open source sEMG design, able to record muscle bio-potentials concurrently to electrical stimulation. The open source, low-cost nature of the design provides accessibility to researchers without the time and cost associated with design development. The design has been tested on the forearms of four able-bodied subjects during 25 Hz constant current stimulation, and has been shown to record subject volitional sEMG and M-wave without saturation.

Intraoperative transcranial facial motor evoked potential monitoring in surgery of cerebellopontine angle tumors predicts early and late postoperative facial nerve function

ObjectiveWe propose a novel method that predicts facial nerve function (FNF) calculated from the drop and recovery of facial motor evoked potential (FMEP) amplitude ratio during the surgery of cerebellopontine angle tumors. MethodsWe enrolled 73 patients with cerebellopontine angle tumor, and used a biphasic, constant current, and suprathreshold stimulation (BCS) protocol to record FMEP of the orbicularis oris. We measured the intraoperative minimum-to-baseline amplitude ratio (MBR), the final-to-baseline amplitude ratio (FBR), and the recovery value (RV). RV was measured by subtracting MBR from FBR. Using those values, we evaluated FNF both at early postoperative (EP) and late postoperative (LP) periods. ResultsWe successfully obtained 62 FMEP readings. Facial palsies occurred in 22 patients during the EP period, and 14 patients recovered during the LP period. Both MBR and FBR showed a significant correlation with FNF in the EP period. RV showed a good predictive power of FNF recovery during the LP period for the first time. ConclusionsRV is a new and useful predictor of FNF recovery. MBR can be an intraoperative predictor of FNF in the EP period. SignificanceFNF outcome in the early and late postoperative periods can be predicted by FMEP.

Silenced SOX2-OT alleviates ventricular arrhythmia associated with heart failure by inhibiting NLRP3 expression via regulating miR-2355-3p.

BackgroundNucleotide‐binding oligomerization domain‐like receptor family pyrin domain containing 3 (NLRP3) inflammasomes are the most important factors in ventricular arrhythmia associated with heart failure (VA‐HF). However, how the relationship between lncRNA and NLRP3 inflammasomes is regulated in VA‐HF has not been investigated in detail. Thus, we aimed to determine the effects of SOX2‐overlapping transcripts (SOX2‐OT) by targeting NLRP3 in rats with VA‐HF.MethodsWe established rats (SPF, male, weight: 240 ± 10 g) with VA‐HF by aortic coarctation and constant‐current stimulation, then injected them with small interfering SOX2‐OT and anti‐miR‐2355‐3p. Six weeks later, SOX2‐OT and miR‐2355‐3p expression was measured using the quantitative reverse transcriptase‐polymerase chain reaction and NLRP3, ASC, caspase‐1, IL‐1β, and TGF‐β1 expression were measured by Western blot analysis; the ventricular chambers were histopathologically analyzed by staining with hematoxylin and eosin, Masson trichrome, and Picro Sirius Red and reactive oxygen species (ROS) levels were assessed by flow cytometry. The targeting relationship between miR‐2355‐3p and SOX2‐OT or NLRP3 was verified using dual‐luciferase reporter gene assays.ResultsThe expression of SOX2‐OT and levels of NLRP3 inflammasomes gradually increased in normal rats, and in those with heart failure and with VA‐HF. Silencing SOX2‐OT expression inhibited NLRP3, ASC, caspase‐1, IL‐1β, and TGF‐β1 expression and ROS production, reduced the degrees of cardiomyocyte necrosis and fibrosis and alleviated cardiac dysfunction in rats with VA‐HF. MicroR‐2355‐3p can bind the SOX2‐OT and the 3′‐untranslated region of NLRP3. Inhibiting miR‐2355‐3p reversed the effect of SOX2‐OT in rats with VA‐HF.ConclusionsSilencing SOX2‐OT alleviated cardiac dysfunction in rats by reducing the activation of NLRP3 inflammasomes via regulating miR‐2355‐3p.

Intraoperative Lumbar Muscle Motor Evoked Potential Monitoring With Transcortical Stimulation

Stimulating electrodes for lower extremity motor-evoked potential (LE-MEP) monitoring with transcortical stimulation are usually placed on the medial side of motor cortex convexity, which is not lower extremity but lumbar motor area. Lumbar MEP may be elicited with lower stimulation intensity than LE-MEP through this location, and it is useful to monitor lower extremity motor function intraoperatively. Intraoperative lumbar and LE-MEP monitoring with transcortical stimulation during surgery of 12 patients with lesions involving the motor cortex from January 2012 to February 2019 at Shinshu University Hospital were reviewed retrospectively. Stimulations were delivered by a train of 5 pulses of anodal constant current stimulation. Stimulating electrode position was determined by motor cortex mapping. Recording needle electrodes were placed on bilateral lumbar muscles and contralateral leg muscles. The threshold-level stimulation method was used for MEP monitoring. The thresholds, monitoring result, and postoperative motor function of lumbar and lower extremities were compared. The mean baseline thresholds were 19.9 ± 8.9 mA for lumbar MEP and 26.5 ± 11.5 mA for LE-MEP (P= 0.02). Patterns of intraoperative monitoring changes were the same between lumbar and LE-MEP monitoring. Lumbar MEP was stimulated with lower stimulation intensity than the LE-MEP with the same intraoperative pattern of waveform changes in 12 patients. Lumbar MEP monitoring may be useful for preserving the corticospinal tract of lower extremities intraoperatively.

Deep Brain Stimulation Impedance Decreases Over Time Even When Stimulation Settings Are Held Constant.

Objectives: To study whether and to what extent the therapeutic impedance and current change under long-term deep brain stimulation (DBS) with constant stimulation settings, which could inform the role of constant current stimulation.Methods: Therapy impedance and current measurements were retrospectively collected from patients with Parkinson’s disease (PD) undergoing DBS of the subthalamic nucleus (STN) or essential tremor (ET) undergoing ventral intermediate nucleus (VIM). Baseline and follow-up measurements were obtained for intervals of at least 6 months without changes in stimulation settings. The single longest interval of constant stimulation for each electrode was included. Temporal trends in impedance and current were analyzed as absolute and relative differences and as the rate of change.Results: Impedance and current data from 79 electrodes (60 in STN, 19 in VIM) in 44 patients (32 with PD, 12 with ET) met inclusion criteria. The duration between baseline and follow-up measurements with constant stimulation settings was 17 months (median, with an interquartile range of 12–26 months) in the mixed group. Therapy impedance decreased by 27 ± 12 Ω/year (mean ± 2 standard errors; p < 0.0001), and therapy current increased at a rate of 0.142 ± 0.063 mA/year (p < 0.0001). Similar results were observed in the STN and VIM subgroups.Conclusions: Impedance decreases gradually over time, even when stimulation settings are kept constant. The rate of decrease is smaller than previously reported, suggesting that changes in stimulation settings contribute to impedance drift. Stimulation-independent impedance drift is gradual but relevant to constant-current programming.

Cerebellopontine Angle Surgery Assisted by Continuous Mapping of the Facial Nerve Via the Ultrasonic Aspirator.

Cerebellopontine angle (CPA) surgery carries the risk of lesioning the facial nerve. The goal of preserving the integrity of the facial nerve is usually pursued with intermittent electrical stimulation using a handheld probe that is alternated with the resection. We report our experience with continuous electrical stimulation delivered via the ultrasonic aspirator (UA) used for the resection of a series of vestibular schwannomas. A total of 17 patients with vestibular schwannomas, operated on between 2010 and 2018, were included in this study. A constant-current stimulator was coupled to the UA used for the resection, delivering square-wave pulses throughout the resection. The muscle responses from upper and lower face muscles triggered by the electrical stimulation were displayed continuously on multichannel neurophysiologic equipment. The careful titration of the electrical stimulation delivered through the UA while tapering the current intensity with the progression of the resection was used as the main strategy. All operations were performed successfully, and facial nerve conduction was maintained in all patients except one, in whom a permanent lesion of the facial nerve followed a miscommunication to the neurosurgeon. The coupling of the electrical stimulation to the UA provided the neurosurgeon with an efficient and cost-effective tool and allowed a safe resection. Positive responses were obtained from the facial muscles with low current intensity (lowest intensity: 0.1 mA). The availability of a resection tool paired with a stimulator allowed the surgeon to improve the surgical workflow because fewer interruptions were necessary to stimulate the facial nerve via a handheld probe.

Activated iridium oxide film (AIROF) electrodes for neural tissue stimulation

Objective. Iridium oxide films are commonly used as a high charge-injection electrode material in neural devices. Yet, few studies have performed in-depth assessments of material performance versus film thickness, especially for films grown on three-dimensional (instead of planar) metal surfaces in neutral pH electrolyte solutions. Further, few studies have investigated the driving voltage requirements for constant-current stimulation using activated iridium oxide (AIROF) electrodes, which will be a key constraint for future use in wirelessly powered neural devices. Approach. In this study, iridium microwire probes were activated by repeated potential pulsing in room temperature phosphate buffered saline (pH 7.1–7.3). Electrochemical measurements were recorded in three different electrolyte conditions for probes with different geometric surface areas (GSAs) as the AIROF thickness was increased. Main results. Maintaining an anodic potential bias during the inter-pulse interval was required for AIROF electrodes to deliver charge levels considered necessary for neural stimulation. Potential pulsing for 100–200 cycles was sufficient to achieve charge injection levels of 2.5 mC cm−2 (50 nC/phase in a biphasic pulse) in PBS with 2000 µm2 iridium probes. Increasing the electrode surface area to 3000 µm2 and 4000 µm2 significantly increased charge-injection capacity, reduced the driving voltage required to deliver a fixed amount of charge, and reduced polarization of the electrodes during constant-current pulsing. Significance. This study establishes methods for choosing an activation protocol and a desired GSA for three-dimensional iridium electrodes suitable for neural tissue insertion and stimulation, and provides guidelines for evaluating electrochemical performance of AIROF using model saline solutions.

In Vivo Intracellular Recording of Type-Identified Rat Spinal Motoneurons During Trans-Spinal Direct Current Stimulation.

Intracellular recording of spinal motoneurons in vivo provides a "gold standard" for determining the cells' electrophysiological characteristics in the intact spinal network and holds significant advantages relative to classical in vitro or extracellular recording techniques. An advantage of in vivo intracellular recordings is that this method can be performed on adult animals with a fully mature nervous system, and therefore many observed physiological mechanisms can be translated to practical applications. In this methodological paper, we describe this procedure combined with externally applied constant current stimulation, which mimics polarization processes occurring within spinal neuronal networks. Trans-spinal direct current stimulation (tsDCS) is an innovative method increasingly used as a neuromodulatory intervention in rehabilitation after various neurological injuries as well as in sports. The influence of tsDCS on the nervous system remains poorly understood and the physiological mechanisms behind its actions are largely unknown. The application of the tsDCS simultaneously with intracellular recordings enables us to directly observe changes of motoneuron membrane properties and characteristics of rhythmic firing in response to the polarization of the spinal neuronal network, which is crucial for the understanding of tsDCS actions. Moreover, when the presented protocol includes the identification of the motoneuron with respect to an innervated muscle and its function (flexor versus extensor) as well as the physiological type (fast versus slow) it provides an opportunity to selectively investigate the influence of tsDCS on identified components of spinal circuitry, which seem to be differently affected by polarization. The presented procedure focuses on surgical preparation for intracellular recordings and stimulation with an emphasis on the steps which are necessary to achieve preparation stability and reproducibility of results. The details of the methodology of the anodal or cathodal tsDCS application are discussed while paying attention to practical and safety issues.

Both reaching and grasping are impacted by temporarily induced paresthesia

Along with visual feedback, somatosensory feedback provides the nervous system with information regarding movement performance. Somatosensory system damage disrupts the normal feedback process, which can lead to a pins and needles sensation, or paresthaesia, and impaired movement control. The present study assessed the impact of temporarily induced median nerve paresthaesia, in individuals with otherwise intact sensorimotor function, on goal-directed reaching and grasping movements. Healthy, right-handed participants performed reach and grasp movements to five wooden Efron shapes, of which three were selected for analysis. Participants performed the task without online visual feedback and in two somatosensory conditions: 1) normal; and 2) disrupted somatosensory feedback. Disrupted somatosensory feedback was induced temporarily using a Digitimer (DS7AH) constant current stimulator. Participants’ movements to shapes 15 or 30 cm to the right of the hand’s start position were recorded using a 3 D motion analysis system at 300 Hz (Optotrak 3 D Investigator). Analyses revealed no significant differences for reaction time. Main effects for paresthaesia were observed for temporal and spatial aspects of the both the reach and grasp components of the movements. Although participants scaled their grip aperture to shape size under paresthaesia, the movements were smaller and more variable. Overall participants behaved as though they perceived they were performing larger and faster movements than they actually were. We suggest the presence of temporally induced paresthaesia affected online control by disrupting somatosensory feedback of the reach and grasp movements, ultimately leading to smaller forces and fewer corrective movements.

Implementation of New Technology in Patients with Chronic Deep Brain Stimulation: Switching from Non-Rechargeable Constant Voltage to Rechargeable Constant Current Stimulation

Introduction: Deep brain stimulation (DBS) for movement disorders has been mainly performed with constant voltage (CV) technology. More recently also constant current (CC) systems have been developed which theoretically might have additional advantages. Furthermore, rechargeable (RC) system implantable pulse generators (IPG) are increasingly being used rather than the former solely available non-rechargeable (NRC) IPGs. Objective: To provide a systematic investigation how to proceed and adapt settings when switching from CV NRC to CC RC technology. Methods: We prospectively collected data from 11 consecutive patients (10 men, mean age at DBS implantation 52.6 ± 14.0 years) with chronic DBS for dystonia (n = 7), Parkinson disease (n = 3), and essential tremor (n = 1) who underwent IPG replacement switching from a CV NRC system (Activa® PC; Medtronic®) to a CC RC system (Vercise® RC; Boston Scientific®). Systematic assessments before and after IPG replacement were performed. Results: DBS technology switching at the time of IPG replacement due to battery depletion was at a mean of 108.5 ± 46.2 months of chronic DBS. No perioperative complications occurred. Clinical outcome was stable with overall mild improvements or deteriorations, which could be dealt with in short-term follow-up. Patients were satisfied with the new RC IPG. Conclusions: This study confirms both the safety and feasibility of switching between different DBS technologies (CV to CC, NRC to RC, different manufacturers) in patients with chronic DBS. Furthermore, it shows how the management can be planned using available information from the previous DBS settings. Individual assessment is needed and might partly be related to the DBS target and the underlying disease. MR safety might be a problem with such hybrid systems.