Location Of Stimulating Electrode Research Articles

Forward Electric Stimulation-Induced Interference in Intracochlear Electrocochleography of Acoustic Stimulation in the Cochlea of Guinea Pigs.

Electric-acoustic stimulation (EAS) uses amplified sound by a hearing aid to stimulate an apical low-frequency region of the cochlea and electrical current from a cochlear implant (CI) to stimulate the basal high-frequency region. EAS recipients had significantly improved speech perception, music appreciation, and hearing function in noise compared to those relying on CI electrical stimulation (ES) alone. However, the interaction between basal ES and apical acoustic stimulation (AS) in the cochlea potentially affects EAS advantages. To investigate ES-AS interaction, we designed a system that recorded the electrically evoked compound action potential (ECAP) and the auditory evoked potential (AEP). We used an intracochlear electrode array to deliver ES at the basal cochlea and detect intracochlear electrocochleography (iECochG) generated from apical AS. Within iECochG, 3 or 6 dB (double or quadruple intensity of ECAP threshold) electric stimulation, 1 ms-forward ES significantly increased CAP amplitudes of 4 kHz/20 dB AS compared to 0 dB ES. Notably, 1 ms-forward 3 dB ES significantly increased CAP amplitudes of 4 kHz/20 dB AS, while 3 or 5 ms-forward ES did not change the CAP amplitudes. The elevation in CAP amplitude of 40 dB/4 kHz AS induced by 1 ms-forward 3 dB ES was significantly lower than that in 20 dB/4 kHz AS. With 1 ms-forward 3 dB ES, AS frequency and stimulating electrode location have no significant impact on relative CAP amplitudes of 20 dB AS. These results suggest that the basal forward ES and the following apical AS could produce a cumulative effect on the auditory nerve response.

Injectable conductive hydrogel can reduce pacing threshold and enhance efficacy of cardiac pacemaker.

Background: Pacemaker implantation is currently used in patients with symptomatic bradycardia. Since a pacemaker is a lifetime therapeutic device, its energy consumption contributes to battery exhaustion, along with its voltage stimulation resulting in local fibrosis and greater resistance, which are all detrimental to patients. The possible resolution for those clinical issues is an injection of a conductive hydrogel, poly-3-amino-4-methoxybenzoic acid-gelatin (PAMB-G), to reduce the myocardial threshold voltage for pacemaker stimulation. Methods: PAMB-G is synthesized by covalently linking PAMB to gelatin, and its conductivity is measured using two-point resistivity. Rat hearts are injected with gelatin or PAMB-G, and pacing threshold is evaluated using electrocardiogram and cardiac optical mapping. Results: PAMB-G conductivity is 13 times greater than in gelatin. The ex vivo model shows that PAMB-G significantly enhances cardiac tissue stimulation. Injection of PAMB-G into the stimulating electrode location at the myocardium has a 4 times greater reduction of pacing threshold voltage, compared with electrode-only or gelatin-injected tissues. Multi-electrode array mapping reveals that the cardiac conduction velocity of PAMB-G group is significantly faster than the non- or gelatin-injection groups. PAMB-G also reduces pacing threshold voltage in an adenosine-induced atrial-ventricular block rat model. Conclusion: PAMB-G hydrogel reduces cardiac pacing threshold voltage, which is able to enhance pacemaker efficacy.

Arc protein expression after unilateral intracranial self-stimulation of the medial forebrain bundle is upregulated in specific nuclei of memory-related areas

BackgroundIntracranial Self-Stimulation (ICSS) of the medial forebrain bundle (MFB) is a deep brain stimulation procedure, which has a powerful enhancement effect on explicit and implicit memory. However, the downstream synaptic plasticity events of MFB-ICSS in memory related areas have not been described thoroughly. This study complements previous work studying the effect of MFB-ICSS on the expression of the activity-regulated cytoskeleton-associated (Arc) protein, which has been widely established as a synaptic plasticity marker. We provide new integrated measurements from memory related regions and take possible regional hemispheric differences into consideration.ResultsArc protein expression levels were analyzed 4.5 h after MFB-ICSS by immunohistochemistry in the hippocampus, habenula, and memory related amygdalar and thalamic nuclei, in both the ipsilateral and contralateral hemispheres to the stimulating electrode location. MFB-ICSS was performed using the same paradigm which has previously been shown to facilitate memory. Our findings illustrate that MFB-ICSS upregulates the expression of Arc protein in the oriens and radiatum layers of ipsilateral CA1 and contralateral CA3 hippocampal regions; the hilus bilaterally, the lateral amygdala and dorsolateral thalamic areas as well as the central medial thalamic nucleus. In contrast, the central amygdala, mediodorsal and paraventricular thalamic nuclei, and the habenular complex did not show changes in Arc expression after MFB-ICSS.ConclusionsOur results expand our knowledge of which specific memory related areas MFB-ICSS activates and, motivates the definition of three functionally separate groups according to their Arc-related synaptic plasticity response: (1) the hippocampus and dorsolateral thalamic area, (2) the central medial thalamic area and (3) the lateral amygdala.

Differential electrical responses in retinal ganglion cell subtypes: effects of synaptic blockade and stimulating electrode location

Objective. Visual prostheses have shown promising results in restoring visual perception to blind patients. The ability to differentially activate retinal ganglion cell (RGC) subtypes could further improve the efficacy of these medical devices. Approach. Using whole-cell patch clamp, we investigated membrane potential differences between ON and OFF RGCs in the mouse retina when their synaptic inputs were blocked by synaptic blockers, and examined the differences in stimulation thresholds under such conditions. By injecting intracellular current, we further confirmed the relationship between RGC stimulation thresholds and resting membrane potentials (RMPs). In addition, we investigated the effects of stimulating electrode location on the differences in stimulation thresholds between ON and OFF RGCs. Main results. With synaptic blockade, ON RGCs became significantly more hyperpolarized (from −61.8 ± 1.4 mV to −70.8 ± 1.6 mV), while OFF RGCs depolarized slightly (from −60.5 ± 0.7 mV to −58.6 ± 0.9 mV). RGC stimulation thresholds were negatively correlated with their RMPs (Pearson r value: −0.5154; p-value: 0.0042). Thus, depriving ON RGCs of synaptic inputs significantly increased their thresholds (from 14.7 ± 1.3 µA to 22.3 ± 2.1 µA) over those of OFF RGCs (from 13.2 ± 0.7 µA to 13.1 ± 1.1 µA). However, with control solution, ON and OFF RGC stimulation thresholds were not significantly different. Finally, placement of the stimulating electrode away from the axon enhanced differences in stimulation thresholds between ON and OFF RGCs, facilitating preferential activation of OFF RGCs. Significance. Since ON and OFF RGCs have antagonistic responses to natural light, achieving differential RGC activation could convey more natural visual information, leading to better visual prosthesis outcomes.

Clinical Paresthesia Atlas Illustrates Likelihood of Coverage Based on Spinal Cord Stimulator Electrode Location

Concordant paresthesia coverage is an independent predictor of pain relief following spinal cord stimulation (SCS). Using aggregate data, our objective is to produce a map of paresthesia coverage as a function of electrode location in SCS. This retrospective analysis used x-rays, SCS programming data, and paresthesia coverage maps from the EMPOWER registry of SCS implants for chronic neuropathic pain. Spinal level of dorsal column stimulation was determined by x-ray adjudication and active cathodes in patient programs. Likelihood of paresthesia coverage was determined as a function of stimulating electrode location. Segments of paresthesia coverage were grouped anatomically. Fisher's exact test was used to identify significant differences in likelihood of paresthesia coverage as a function of spinal stimulation level. In the 178 patients analyzed, the most prevalent areas of paresthesia coverage were buttocks, anterior and posterior thigh (each 98%), and low back (94%). Unwanted paresthesia at the ribs occurred in 8% of patients. There were significant differences in the likelihood of achieving paresthesia, with higher thoracic levels (T5, T6, and T7) more likely to achieve low back coverage but also more likely to introduce paresthesia felt at the ribs. Higher levels in the thoracic spine were associated with greater coverage of the buttocks, back, and thigh, and with lesser coverage of the leg and foot. This paresthesia atlas uses real-world, aggregate data to determine likelihood of paresthesia coverage as a function of stimulating electrode location. It represents an application of "big data" techniques, and a step toward achieving personalized SCS therapy tailored to the individual's chronic pain.

Electrically Evoked Compound Action Potentials Recorded From the Sheep Spinal Cord

The study aims to characterize the electrical response of dorsal column axons to depolarizing stimuli to help understand the mechanisms of spinal cord stimulation (SCS) for the relief of chronic pain. We recorded electrically evoked compound action potentials (ECAPs) during SCS in 10 anesthetized sheep using stimulating and recording electrodes on the same epidural SCS leads. A novel stimulating and recording system allowed artifact contamination of the ECAP to be minimized. The ECAP in the sheep spinal cord demonstrates a triphasic morphology, with P1, N1, and P2 peaks. The amplitude of the ECAP varies along the length of the spinal cord, with minimum amplitudes recorded from electrodes positioned over each intervertebral disc, and maximum amplitudes recorded in the midvertebral positions. This anatomically correlated depression of ECAP also correlates with the areas of the spinal cord with the highest thresholds for stimulation; thus regions of weakest response invariably had least sensitivity to stimulation by as much as a factor of two. The choice of stimulating electrode location can therefore have a profound effect on the power consumption for an implanted stimulator for SCS. There may be optimal positions for stimulation in the sheep, and this observation may translate to humans. Almost no change in conduction velocity (∼100 ms) was observed with increasing currents from threshold to twice threshold, despite increased Aβ fiber recruitment. Amplitude of sheep Aβ fiber potentials during SCS exhibit dependence on electrode location, highlighting potential optimization of Aβ recruitment and power consumption in SCS devices.

Intraspinal Microstimulation Excites Multisegmental Sensory Afferents at Lower Stimulus Levels Than Local α-Motoneuron Responses

Microstimulation within the motor regions of the spinal cord is often assumed to activate motoneurons and propriospinal neurons close to the electrode tip. However, previous work has shown that intraspinal microstimulation (ISMS) in the gray matter activates sensory afferent axons as well as alpha-motoneurons (MNs). Here we report on the recruitment of sensory afferent axons and MNs as ISMS amplitudes increased. Intraspinal microstimulation was applied through microwires implanted in the dorsal horn, intermediate region and ventral horn of the L(5)-L(7) segments of the spinal cord in four acutely decerebrated cats, two of which had been chronically spinalized. Activation of sensory axons was detected with electroneurographic recordings from dorsal roots. Activation of MNs was detected with electromyographic (EMG) recordings from hindlimb muscles. Sensory axons were nearly always activated at lower stimulus levels than MNs irrespective of the stimulating electrode location. EMG response latencies decreased as ISMS stimulus intensities increased, suggesting that MNs were first activated transsynaptically and then directly as intensity increased. ISMS elicited antidromic activity in dorsal root filaments with entry zones up to 17 mm rostral and caudal to the stimulation sites. We posit that action potentials elicited in localized terminal branches of afferents spread antidromically to all terminal branches of the afferents and transsynaptically excite MNs and interneurons far removed from the stimulation site. This may help explain how focal ISMS can activate many MNs of a muscle even though they are distributed in long thin columns.

Can Conventional Peripheral Nerve Stimulators Induce Direct Muscle Depolarization?

In Response: We thank Dr. Kopman for his thoughtful comments on our article. He expresses quite nicely the differences between the excitability of nerve and muscle by comparing their strength-duration curves. These curves show the current (y-axis) that must be applied for a given stimulus duration (x-axis) to depolarize either nerve or muscle. The figure shows that, irrespective of duration of stimulus applied, muscle requires a larger current than nerve to be depolarized, and the difference is approximately one order of magnitude. However, this difference between nerve and muscle is greater for short stimuli. In other words, the chronaxie, which is the stimulus duration required to elicit a response at twice the rheobase, is greater for muscle than nerve. Dr. Kopman suggests correctly that increasing stimulus duration could decrease the difference in excitability between nerve and muscle (1). However, we think that an increase in stimulus duration from 0.2 to 0.3 ms is unlikely to affect the likelihood of direct muscle stimulation. Dr. Kopman did not accurately reproduce Mortimer's (2) Figure. The figure should have been drawn with a logarithmic x-axis. As shown in the redrawn figure (Fig. 1), the 0.2-ms and 0.3-ms durations are both in the range where the excitability gap between nerve and muscle is wide. The chronaxie is at least 10 times less in nerve (1 ms) than in muscle (>10 ms).Figure 1.: Redrawn figure from Mortimer 2). The difference between currents required to stimulate nerve and muscle with pulse durations of 0.2 and 0.3 ms is indicated.There are few data in the peer-reviewed literature about strength-duration curves in paralyzed muscle. In 1974, paralyzed muscle of cats was stimulated at supramaximal current for nerve stimulation. The resulting contraction was 3.5%–7% of that obtained in non paralyzed muscle; the smaller number was obtained with shorter duration stimulation (3). These data were obtained with needle electrodes, and the use of surface electrodes might produce different results. Recently, the differential response to short and long pulses was used in the diagnosis of denervation, as denervated muscle responds only to long (1 ms to >20 ms) pulses (4). However, the difference in excitability between nerve and muscle is not infinite, and direct muscle stimulation may occur in practice with stimulation at the wrist or at the hand. In our study, (5) we had evidence of direct muscle stimulation with stimulation at the wrist in two patients. In practice, such an occurrence can be detected by 1) absence of fade, 2) small amplitude of the twitch, and 3) disappearance of the response when the location of stimulating electrodes is changed (Fig. 2).Figure 2.: Original tracings from a patient who showed direct muscle stimulation with electrodes at the wrist but not at the hand. The dose of rocuronium was 0.6 mg/kg. Direct muscle stimulation in the presence of a neuromuscular blocking drug can be recognized by the small amplitude of response (in this case 3%), and lack of fade. The response disappeared when stimulating electrodes were applied elsewhere. Only two such occurrences were observed in our study, with wrist stimulation in both cases.Marie-Eve Nepveu, MD François Donati, PhD, MD, FRCPC Louis-Philippe Fortier, MSc, MD, FRCPC Department of Anesthesia Université de Montréal Hôpital Maisonneuve-Rosemont Montréal, Québec, Canada [email protected]

Identifying the Source of Radial Nerve Afferents that Inhibit Biceps Brachii

Electrical stimulation of the brachioradialis branch of the radial nerve inhibits the discharge of motor units in biceps brachii. Because the distal portion of brachialis is also innervated by a branch of the radial nerve, however, there is uncertainty over the origin of the inhibitory projection to the motor units in biceps brachii. PURPOSE: To determine the extent to which inhibition of the biceps brachii motor neuron pool with radial nerve stimulation is mediated by afferent projections from the brachioradialis or brachialis. METHODS: Stimulating electrode location was optimized for both the brachioradialis and brachialis branches of the radial nerve by observing the electrically evoked motor responses from the interference electromyogram of both muscles. Six male subjects produced low elbow flexion forces (2.8 ± 1.6 %MVC) to maintain the discharge of a biceps brachii motor unit at 11.1 ±0.8 pps. Stimulation was applied every 2 – 3 s with a 30-ms delay after the discharge of the motor unit. Stimulus intensity was 0.9x motor threshold (MT). Pre- and post-stimulus time histograms were constructed from the 108 ±12 stimuli that occurred during the discharge of the motor units. The influence of the two stimulus locations was assessed on the same biceps brachii motor unit. Inhibition was quantified as the percent change from the pre- to post-stimulus interspike intervals. RESULTS: Seven motor units were recorded for each stimulation location. To determine the selectivity of stimulation, motor thresholds were identified for both muscles at each stimulation site. There was a limited capacity to selectively stimulate either nerve branch; the stimulus intensity (0.9x MT) for each muscle corresponded to ∼0.73x MT for the other muscle. Despite this limited selectivity, the magnitude of inhibition on biceps brachii motor units was significantly less (P <0.05) when stimulation was optimized for the brachialis branch of the radial nerve (3.4 %) than the brachioradialis branch (6.5 %). CONCLUSION: These data suggest that either there are fewer inhibitory afferent projections from radial nerve-innervated brachialis than from brachioradialis or that brachialis afferents do not inhibit biceps brachii motor units and the observed inhibition was due to activation of brachioradialis afferents at a lower stimulus intensity. Inhibition of biceps brachii motor units with radial nerve stimulation appears to be primarily mediated by afferents from the brachioradialis muscle. Supported by NINDS R01 NS43275.

Chronic intracochlear electrical stimulation in neonatally deafened cats: Effects of intensity and stimulating electrode location

An earlier study conducted in this laboratory suggested that chronic intracochlear electrical stimulation at moderate current levels can at least partially delay or prevent the retrograde degeneration of primary auditory (spiral ganglion) neurons that otherwise is progressive after neonatal deafness induced by ototoxic drug administration. Increased survival of spiral ganglion neurons was observed within the basal cochlear region near the stimulating bipolar electrode pairs, while in more apical regions there was no significant difference between the stimulated and control cochleas. The mechanisms underlying this maintenance of spiral ganglion neurons induced by chronic electrical stimulation are uncertain, especially since increased neuronal survival was observed over broader sectors of the ganglion than would be expected to be directly activated by the bipolar electrodes and moderate stimulation intensity (6 dB above electrically evoked auditory brainstem response threshold) used. In this report, data are presented from a second series of neonatally deafened and chronically stimulated cats. The parameters for chronic electrical stimulation were manipulated in two simple ways. First, the intensity of the electrical stimulus was reduced from the earlier study, while the duration of chronic stimulation periods was increased, and secondly, two different intracochlear positions of stimulating electrodes were employed in different experimental groups. Results indicate that electrical stimulation of the cochlea at an extremely low intensity (2 dB above electrically evoked auditory brainstem response threshold) is sufficient to at least partially prevent or delay ganglion cell degeneration in the deafened cochlea. In addition, data suggest a differential distribution of the maintained or conserved ganglion cells, such that when the stimulating electrode pair was positioned near the base of the cochlea increased ganglion survival was observed in a more basal cochlear sector, while stimulation at a more apical site resulted in increased neuronal survival extending to more apical regions.

A comparison of the acoustical and electrically induced auditory brainstem response in the guinea pig

Electrical and Acoustical Auditory Brainstem Responses (ABRs) in a guinea pig model are compared in order to better define the characteristics of electrical stimulation. Also, the effects of the stimulating electrode location are being investigated because of its implications for cochlear implant design. The active electrodes are positioned in the basal and apical turns, while the return electrodes are placed in the eustachian tube and temporalis muscle. ABR morphology, wave latencies, and central conduction time are among the parameters studied. Electrode placement appears to have little effect on wave latencies or amplitudes. The acoustical and electrical wave morphologies differ. Latencies and central conduction time are shorter for electrical than for acoustical stimulation.

Functional validation of projection topography in the nigrostriatal dopamine system

Anatomical investigations have revealed that the nigrostriatal pathway is topographically organised. In two experiments, nigrostriatal topography was investigated with catecholamine specific procedures, using paradigms which reflect the functional activity of dopaminergic neurones. Data were analysed with the intention of discovering possible relationships between the mesencephalic location of stimulating electrodes or injection cannulae, the extent and location of dopamine histofluorescence depletion within the striatum, and the effects of amphetamine and apomorphine on rotational behaviour. In animals pretreated with 250 mg/kgα-methyl- p-tyrosine it was found that unilateral stimulation with medially-placed nigral electrodes produced maximal depletion of dopamine histofluorescence in anterior dorso-medial regions of the striatum, while laterally-located electrodes principally depleted posterior, ventro-lateral areas. In the second experiment, 2 μg of 6-hydroxydopamine in a volume of 0.5 μl was injected unilaterally at varying loci within the ventral midbrain of animals pre-treated with desmethylimipramine (25 mg/kg). It was discovered that the lateral injection coordinate was significantly associated with both the extent and location of the depletion of dopamine-related fluorescence from the ipsilateral striatum. Rotational behaviour, induced by dopamine-agonists was related firstly, to the overall extent of dopamine depletion from the striatum, and secondly, the contraversive turning induced by apomorphine in particular was related to the dorsoventral coordinate of the mesencephalic 6-hydroxydopamine injection. The results provide functional validation for the pattern of topographical projection within the nigrostriatal dopaminergic system proposed on the basis of intracellular tracing techniques.