Compound Action Potential Amplitude Research Articles

Neuropathology of vitamin B12 deficiency in the Cd320-/- mouse.

In humans, vitamin B12 deficiency causes peripheral and CNS manifestations. Loss of myelin in the peripheral nerves and the spinal cord (SC) contributes to peripheral neuropathy and motor deficits. The metabolic basis for the demyelination and brain disorder is unknown. The transcobalamin receptor-knockout mouse ( Cd320-/-) develops cobalamin (Cbl) deficiency in the nervous system, with mild anemia. A decreased S-adenosylmethionine: S-adenosylhomocysteine ratio and increased methionine were seen in the brain with no significant changes in neurotransmitter metabolites. The structural pathology in the SC presented as loss of myelin in the axonal tracts with inflammation. The sciatic nerve (SN) showed increased nonuniform, internodal segments suggesting demyelination, and remyelination in progress. Consistent with these changes, the Cd320-/- mouse showed an increased latency to thermal nociception. Further, lower amplitude of compound action potential in the SN suggested that the functional capacity of the heavily myelinated axons were preferentially compromised, leading to loss of peripheral sensation. Although the metabolic basis for the demyelination and the structural and functional alterations of the nervous system in Cbl deficiency remain unresolved, the Cd320-/- mouse provides a unique model to investigate the pathologic consequences of vitamin B12 deficiency. -Arora, K., Sequeira, J. M., Alarcon, J. M., Wasek, B., Arning, E., Bottiglieri, T., Quadros, E. V. Neuropathology of vitamin B12 deficiency in the Cd320-/- mouse.

Electro-Physiology of Coupling Model and Its Impact on Naja Kaouthia Venom Treated Sciatic Nerves of Toad.

Demyelination in peripheral nerves causes dysfunction of slowing down and stoppage of nerve impulses causing many neurological diseases, such as chronic inflammatory demyelinating polyneuropathy, Guillain-Barre syndrome, etc. This paper aims to develop a recovery model having interaction of a demyelinated nerve with a normal myelinated nerve. We validated the model by coupling between peripheral nerve of toad (demyelinated with Naja kaouthia venom) and a normal nerve of toad. An increase in both nerve conduction velocity as well as compound action potential amplitude is observed in the repetition of the experiments indicating gradual recovery of the patients. The significance behind this work is to suppress the malfunctioning of the demyelinated nerve by the normal electro-physiological activity of the normal nerve for speedy recovery using coupling model. The recovery model will be used in the treatment of neurological disorders with the influence of normal neuro physiological properties of a normal adjacent nerve.

Inhibition by non-steroidal anti-inflammatory drugs of compound action potentials in frog sciatic nerve fibers

AimsAlthough antinociception produced by non-steroidal anti-inflammatory drugs (NSAIDs) is partly attributed to nerve conduction inhibition, this has not been thoroughly examined yet. The aim of the present study was to reveal quantitatively how various types of NSAIDs affect compound action potentials (CAPs), a measure of nerve conduction. Main methodsCAPs were recorded from the frog sciatic nerve by using the air-gap method. Key findingsSoaking the sciatic nerve with acetic acid-based NSAIDs (diclofenac and aceclofenac) reduced the peak amplitude of CAP in a concentration-dependent manner; their IC50 values were 0.94 and 0.47 mM, respectively. Other acetic acid-based NSAIDs (indomethacin, acemetacin and etodolac) also inhibited CAPs [the extent of inhibition: some 40% (1 mM), 40% (0.5 mM) and 15% (1 mM), respectively], except for sulindac and felbinac at 1 mM that had no effects on CAP peak amplitudes. A similar inhibition was produced by fenamic acid-based NSAIDs [tolfenamic acid (IC50 = 0.29 mM), meclofenamic acid (0.19 mM), flufenamic acid (0.22 mM) and mefenamic acid] which are similar in chemical structure to diclofenac and aceclofenac; their derivatives (2,6-dichlorodiphenylamine and N-phenylanthranilic acid) also inhibited. On the other hand, salicylic acid-based (aspirin), propionic acid-based (ketoprofen, naproxen, ibuprofen, loxoprofen and flurbiprofen) and enolic acid-based (meloxicam and piroxicam) NSAIDs had no effects on CAP peak amplitudes. SignificanceAt least a part of antinociception produced by NSAIDs used as a dermatological drug to alleviate pain may be attributed to their inhibitory effects on nerve conduction, which depend on the chemical structures of NSAIDs.

Boesenbergia rotunda Ethanolic Extract Inhibits Compound Action Potentials via Opioid Receptors

Boesenbergia rotunda, traditionally used to relieve stomach, abdomen, joint, muscle, and rheumatic pain was also reported for its antinociceptive effect on a mouse model. However, the possible pain relief effect of Boesenbergia rotunda ethanolic extract (BREE) via the inhibition to the neural pain pathway remains to be elucidated. This study investigated the inhibitory effect of BREE on compound action potentials (CAPs) and the possible involvement of the opioid receptors. The changes in the CAPs amplitudes of the frog’s sciatic nerves were evaluated following the exposure to three different dosages of BREE (1, 3 and 10 mg/ml and morphine (3 mg/ml). In another set of experiment, the nerves were pretreated with a non-selective opioid receptor antagonist, naloxone (0.1 mg/ml), before exposing the nerve to BREE (1 mg/ml) to investigate the involvement of opioid receptors in the CAPs inhibitory mechanism. The outcome showed a reduction in the CAPs amplitudes when treated with BREE (1, 3 and 10 mg/ml) whereby the effect was reversible. The CAPs inhibition by BREE was absent when the opioid receptors were blocked. Taken together, these findings suggest that BREE-induced CAPs amplitude reduction involves the activation of opioid receptors.

EFFECTS OF SELENIUM ON AXON AND MYELIN HEALING IN AN EXPERIMENTAL SCIATIC NERVE INJURY MODEL

Objective: Although, the neuroprotective effects of selenium are known, its effect on peripheral nerve injury is not clear. The study was aimed to investigate whether selenium prevents axonal and myelin damage in experimental sciatic nerve injury. Materials and Methods: Twenty-eight male Wistar albino rats were divided into four groups (n=7 in each): control (C), selenium (S), injury (I), and selenium-treated injury (SI). Injury was generated by 30 second of compression via Yasargil aneurysm clip on the sciatic nerve of rats in the I and SI groups. Then, selenium was given to the S and SI groups as 1.5 mg/ kg by oral gavage at 1st, 24th, 48th and 72nd hour after surgery. According to the experimental protocol, electrophysiological, histological, and biochemical tests were performed end of the day 4. Results: Whereas the amplitude of compound action potential, nerve conduction velocity, average axon diameter, myelin thickness, myelinated/unmyelinated axons and SOD activity in red blood cells of the I group were significantly lower than those of the C, S and SI groups, the serum MDA levels of the I group were significantly higher than those of the C, S and SI groups. Conclusion: The findings of this study show that selenium decreases axonal and myelin damage after sciatic nerve injury and that this neuroprotective effect of selenium is at least partially mediated by oxidant/antioxidant mechanisms.  

What can stimulus polarity and interphase gap tell us about auditory nerve function in cochlear-implant recipients?

Modeling studies suggest that differences in neural responses between polarities might reflect underlying neural health. Specifically, large differences in electrically evoked compound action potential (eCAP) amplitudes and amplitude-growth-function (AGF) slopes between polarities might reflect poorer peripheral neural health, whereas more similar eCAP responses between polarities might reflect better neural health. The interphase gap (IPG) has also been shown to relate to neural survival in animal studies. Specifically, healthy neurons exhibit larger eCAP amplitudes, lower thresholds, and steeper AGF slopes for increasing IPGs. In ears with poorer neural survival, these changes in neural responses are generally less apparent with increasing IPG. The primary goal of this study was to examine the combined effects of stimulus polarity and IPG within and across subjects to determine whether both measures represent similar underlying mechanisms related to neural health. With the exception of one measure in one group of subjects, results showed that polarity and IPG effects were generally not correlated in a systematic or predictable way. This suggests that these two effects might represent somewhat different aspects of neural health, such as differences in site of excitation versus integrative membrane characteristics, for example. Overall, the results from this study suggest that the underlying mechanisms that contribute to polarity and IPG effects in human CI recipients might be difficult to determine from animal models that do not exhibit the same anatomy, variance in etiology, electrode placement, and duration of deafness as humans.

Parallel Evaluation of Two Potassium Channel Blockers in Restoring Conduction in Mechanical Spinal Cord Injury in Rat.

Myelin damage is a hallmark of spinal cord injury (SCI), and potassium channel blocker (PCB) is proven effective to restore axonal conduction and regain neurological function. Aiming to improve this therapy beyond the U.S. Food and Drug Administration-approved 4-aminopyridine (4-AP), we have developed multiple new PCBs, with 4-aminopyridine-3-methanol (4-AP-3-MeOH) being the most potent and effective. The current study evaluated two PCBs, 4-AP-3-MeOH and 4-AP, in parallel in both ex vivo and in vivo rat mechanical SCI models. Specifically, 4-AP-3-MeOH induced significantly greater augmentation of axonal conduction than 4-AP in both acute and chronic injury. 4-AP-3-MeOH had no negative influence on the electrical responsiveness of rescued axons whereas 4-AP-recruited axons displayed a reduced ability to follow multiple stimuli. In addition, 4-AP-3-MeOH can be applied intraperitoneally at a dose that is at least 5 times higher (5 mg/kg) than that of 4-AP (1 mg/kg) in vivo. Further, 5 mg/kg of 4-AP-3-MeOH significantly improved motor function whereas both 4-AP-3-MeOH (1 and 5 mg/kg) and, to a lesser degree, 4-AP (1 mg/kg) alleviated neuropathic pain-like behavior when applied in rats 2 weeks post-SCI. Based on these and other findings, we conclude that 4-AP-3-MeOH appears to be more advantageous over 4-AP in restoring axonal conduction because of the combination of its higher efficacy in enhancing the amplitude of compound action potential, lesser negative effect on axonal responsiveness to multiple stimuli, and wider therapeutic range in both ex vivo and in vivo application. As a result, 4-AP-3-MeOH has emerged as a strong alternative to 4-AP that can complement the effectiveness, and even partially overcome the shortcomings, of 4-AP in the treatment of neurotrauma and degenerative diseases where myelin damage is implicated.

Hinokitiol inhibits compound action potentials in the frog sciatic nerve

Hinokitiol (β-thujaplicin) is a natural tropolone derivative contained in Chamaecyparis taiwanensis that has various actions including anti-inflammatory activities. Various plant-derived compounds inhibit compound action potentials (CAPs) in a manner dependent on the chemical structure of the compounds; however, the effects of hinokitiol on nerve conduction have not been examined. To determine whether hinokitiol inhibits CAPs and, if so, the chemical structure of hinokitiol that is important in this inhibition, we examined the effects of hinokitiol and its related compounds on fast-conducting CAPs using the frog sciatic nerve and the air-gap method. Hinokitiol concentration-dependently reduced the peak amplitude of CAPs with a half-maximal inhibitory concentration (IC50) value of 0.54mM. A stereoisomer of hinokitiol, γ-thujaplicin, also inhibited CAPs. Although hinokitiol has hydroxyl, carbonyl and isopropyl groups, all of which are bound to its seven-membered ring, tropolone, which lacks the isopropyl group, had no effects on CAPs. Moreover, CAPs were unaffected by kojic acid, which lacks an isopropyl group, and also by guaiazulene, which has an isopropyl group but not carbonyl or hydroxyl groups. Biosol and 4-isopropylphenol, which have isopropyl and hydroxyl groups bound to their six-membered ring, reduced CAP peak amplitudes. This 4-isopropylphenol's activity was more effective than 4-isopropylcyclohexanol and phenol, and less effective than 4-tert-butylphenol and 4-tert-amylphenol; isopropylbenzene had no effects on CAPs. These results indicate that hinokitiol inhibits frog CAPs, possibly through interaction involving its isopropyl, carbonyl and hydroxyl groups. Hinokitiol, therefore, has an ability to inhibit nerve conduction, which contributes partly to the pharmacological actions of hinokitiol.

Compound action potential inhibition produced by various antidepressants in the frog sciatic nerve

Although an inhibition of action potential conduction in nerve fibers possibly contributes to at least a part of antinociception produced by analgesics and the adjuvants, it has not been fully examined yet how the conduction inhibition differs in extent among their drugs. We investigated the effects of various antidepressants used as analgesic adjuvants on compound action potentials (CAPs) recorded from the frog sciatic nerve by using the air-gap method. The results were compared with those of the other adjuvants that were reported previously. Antidepressants, duloxetine (serotonin and noradrenaline reuptake inhibitor, SNRI), fluoxetine (selective serotonin reuptake inhibitor, SSRI), amitriptyline (tricyclic tertiary amine), desipramine (tricyclic secondary amine) and maprotiline (tetracyclic secondary amine), reduced the peak amplitude of the CAP with half-maximal inhibitory concentration (IC50) values of 0.23, 1.5, 0.26, 1.6 and 0.95mM, respectively. Trazodone (non-SNRI, -SSRI, -tricyclic and -tetracyclic antidepressant) at 1.0mM reduced CAP amplitude by about 50%. The duloxetine and amitriptyline values were comparable to those of lamotrigine and carbamazepine (antiepileptics), dexmedetomidine (α2-adrenoceptor agonist) and ropivacaine, levobupivacaine and pramoxine (local anesthetics). The fluoxetine, desipramine, maprotiline and trazodone values were similar to those of oxymetazoline (α2-adrenoceptor agonist) and lidocaine, cocaine, procaine and prilocaine (local anesthetics). The antidepressants’ IC50 values were much larger than that of tetracaine (local anesthetic). In conclusion, the six antidepressants inhibited CAPs with efficacies comparable to some antiepileptics, α2-adrenoceptor agonists and local anesthetics. It was suggested that antidepressants inhibit nerve conduction with efficacies comparable to those of the other adjuvants.

Intraoperative force and electrocochleography measurements in an animal model of cochlear implantation

To preserve residual hearing, techniques for monitoring and reducing the effects of trauma during cochlear implant surgery are being developed. This study examines the relationships between intraoperative recordings (electrode insertion force and electrocochleography), trauma, and hearing loss after cochlear implantation. The study also evaluated the efficacy of intravenous steroids for reducing hearing loss after implantation. Thirty-two normal-hearing guinea pigs were randomly implanted with electrode arrays of differing stiffness (‘hard’ or ‘soft’). These arrays used an intracochlear electrode to record electrode insertion force and electrocochleography responses to a multi-frequency acoustic stimulus during implantation. Additionally, sub-cohorts of animals were administered intravenous saline (‘control’) or dexamethasone (‘steroid’) prior to surgery. Subsequent hearing loss was assessed using electrocochleography recordings from the round window membrane prior to surgery and 4 weeks after implantation. After 4 weeks, cochleae were harvested and imaged with thin sheet laser imaging microscopy. After 4 weeks, compound action potential (CAP) thresholds did not differ between steroid and control groups. The CAP amplitude at low-mid frequencies decreased after implantation with a hard electrode, an effect which was partly negated by administering steroids. A decrease in the ‘intraoperative’ CAP amplitude preceded the reporting of insertion resistance by the surgeon by 5.94 s (±4.03 s SEM). Intraoperative CAP declines were also correlated with higher grades of trauma (r = 0.56, p < 0.01) and greater hearing loss (r = 0.56, p < 0.01). This relationship was not repeated with intraoperative cochlear microphonics. A rise in intraoperative force, which preceded the reporting of resistance by 0.71 s (±0.15 s SEM), was correlated with trauma (r = 0.400, p = 0.04) but not hearing loss (r = 0.297, p = 0.27). Preserving intraoperative CAP amplitudes during implantation was predictive of an atraumatic insertion and reduced post-implantation hearing loss. A rise in force usually preceded the reporting of resistance, although by less than 1 s. These results suggest that intraoperative CAPs may offer a more robust feedback mechanism for improving hearing preservation rates than cochlear microphonic and electrode insertion force recordings, especially considering the rapid changes in insertion force and relatively slow human reaction times. Pre-operative steroids were effective in reversing loss of CAP amplitude with hard electrodes and evoked by lower frequency tones, which suggests a possible role in reducing synaptopathy.

Inhibitory effects of cardamonin on compound action potentials in frog sciatic nerves and the possible involvement of opioidergic pathway

Introduction: Active compounds derived from plants are able to inhibit nerve conduction. Cardamonin, a naturally occurring chalcone, manifests anti-nociceptive, anti-inflammatory and anti-neuropathy properties. Consequently, cardamonin may potentially inhibit nerve action potential, whereby, it affects the nerve conduction. Compound action potential is the sum of the activity which is measured from a nerve trunk. Objective: The study was conducted to investigate the inhibitory effect of cardamonin on compound action potentials and its possible mechanism of action on frog sciatic nerve. Methodology: Compound action potentials were recorded from frog sciatic nerve by using the AD instrument. Sciatic nerve was isolated from the frog and placed in Ringer’s solution. Stimulating electrodes were used to stimulate the nerve and recording electrodes were used to record compound action potentials. Compound action potential of the nerve were recorded before and after treatments [vehicle, cardamonin (0.5, 1 & 2 mg/ml) & morphine (3mg/ml)]. To investigate the involvement of opioidergic system, the nerve were pre-treated with naloxone and followed by cardamonin. All the data were recorded and analysed via LabTutor software. The data were analysed by using Two-way ANOVA followed by Bonferonni’s post hoc test with significant value at P < 0.05. Results: The outcomes showed that all the doses of cardamonin significantly reduced the peak amplitude of compound action potential in frog sciatic nerves. Besides, co-treatment of naloxone and cardamonin significantly (P < 0.001) reversed the effect of cardamonin on peak amplitude of compound action potential, suggesting the involvement of opioid receptors to inhibit nerve conduction. Conclusion: Cardamonin reduces the nerve signal conduction via activation of opioid receptors to modulate pain and contribute to the analgesic effects.

The pattern of involvement of the lower limb nerves in diabetic neuropathy among children with type I diabetes mellitus

Background: Diabetic peripheral neuropathy (DPN) involves both sensory and motor nerves; from pathological point of view it can cause demyelinating neuropathy (evident by increase in latency and decrease in conduction-velocity [CV]) as well as axonal degeneration neuropathy (evident by decrease in amplitude) of compound action potential. However there is controversy on which is the most affected nerve and nerve conduction study (NCS) parameter in DPN.

Maximal number of pre-synaptic ribbons are formed in cochlear region corresponding to middle frequency in mice

Objective: To investigate whether there are more quantitative pre-synaptic ribbons formed in the cochlear region corresponding to middle-frequency in cochlea of mice.Methods: Counts of pre-synaptic ribbons were performed using immunostaining and laser confocal microscopy. Hearing thresholds and function of ribbon synapses were estimated by auditory brain response (ABR) and compound action potential (CAP). Cochlear mapping has been achieved to match the frequencies and corresponding regions along the cochlear spiral.Results: The number of pre-synaptic ribbons in per inner hair cell (IHC) has been found to increase gradually from the base turn, the maximal quantity appeared at the region of 50–70% from the apex. Next, ABR thresholds showed that there was the lowest ABR threshold in the frequency around 8–16 kHz, corresponding to the region of 50–70% from the apex according to the cochlear mapping. Further, CAP amplitudes were estimated, and the maximal value identified at the same frequency (8–16 kHz).Conclusions: Maximal number of pre-synaptic ribbons is formed in the cochlear region of middle frequency in mice, coupling with the lowest ABR threshold and highest CAP amplitudes. Our study shows that the middle frequency (8–16 kHz) could be the most sensitive region to sound stimuli in mice.

Alterations in Auditory Electrophysiological Responses Associated With Temporary Suppression of Tinnitus Induced by Low-Level Laser Therapy: A Before-After Case Series.

Introduction: Tinnitus is the phantom auditory perception of sound in the absence of an external or internal acoustic stimulus. The treatment is difficult due to multiple etiologies and great psychological influence. The purpose of this study was to determine alterations in auditory physiological and electrophysiological responses associated with temporary suppression of tinnitus induced by low-level laser (LLL) irradiation. Methods: This study was conducted on 20 subjects with subjective tinnitus. All subjects signed the informed consent form and satisfied all the study eligibility criteria. Visual analog scale (VAS) for loudness, loudness matching of tinnitus (LMT), pitch matching of tinnitus (PMT), Persian-tinnitus questionnaire (P-TQ) and Persian-tinnitus handicap inventory (P-THI) were conducted pre- and post-low level laser therapy (LLLT) for all the subjects. Electrocochleography (ECochG) and distortion product otoacoustic emissions (DPOAEs) were recorded in 11 subjects. Continuous wave diode lasers, including red (630 nm) and infra-red (808 nm) were applied, and were both designed by the Canadian Optic and Laser (COL) Center. Twelve sessions of laser therapy were performed, 2 sessions per week for each subject. Total dose was 120 Joule/ ear/session. Results: LLL irradiation could cause a significant decrease in subjective tests scores consisting of VAS for loudness, PMT, P-TQ, P-THI, but did not result in a significant improvement of objective evaluating parameters except for compound action potential (CAP) amplitude. Conclusion: LLLT might be a subjectively effective treatment for short-term improvement of tinnitus. Defining a new protocol for optimizing LLLT parameters may be an option to improve parameters of objective tests.

P284 Early differential diagnostic between axonal and demyelinating form of Guillain-Barré syndrome in children

Aim of our work was to determine specificity and sensitivity of conduction studies parameters for differential diagnostics between acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN) in children. Methods 38 children were enrolled: 20 controls (7–14 years old) and 18 patients with AMAN or AIDP, later established according to current criteria. All patients undergo conduction studies on 3–7 day from the first symptoms occurrence. Conduction velocity (CV) and distal compound action potential (CMAP) amplitudes were evaluated for nn. Tibialis, Peroneus, Medianus, Ulnaris;CV and amplitude of sensory nerve action potential (SNAP) were registered for nn Medianus, Suralis, Peroneus superficialis et Ulnaris. ROC-analysis was applied for sensitivity and specificity evaluation. Results Significantly lower SNAP amplitude for n.Medianus was registered in AIDP group comparing with controls and AMAN. For AMAN development, SNAP amplitude for n. Medianus >8.9 μ V was a value with very good predictive ability (AUROC > 0.8), SNAP amplitude for n.Peroneus superficialis >3.6 μ B and CMAP amplitude for n.Peroneus ⩽0.4 m A were values with a good predictive ability (AUROC > 0.7). Conclusions Conduction studies parameters on the early stage of Guillain-Barre syndrome in children are specific enough for differential diagnostics between AMAN and AIDP in children. SNAP amplitudes for n.Medianus >8.9 μ V, n.Peroneus superficialis >3.6 μ A and CMAP amplitude for n.Peroneus ⩽0.4 m A and CV along the motor pathways remains within normal values are parameters that may indicate to AMAN diagnosis.

Prolonged low-level noise-induced plasticity in the peripheral and central auditory system of rats

Prolonged low-level noise exposure alters loudness perception in humans, presumably by decreasing the gain of the central auditory system. Here we test the central gain hypothesis by measuring the acute and chronic physiologic changes at the level of the cochlea and inferior colliculus (IC) after a 75-dB SPL, 10–20-kHz noise exposure for 5weeks. The compound action potential (CAP) and summating potential (SP) were used to assess the functional status of the cochlea and 16 channel electrodes were used to measure the local field potentials (LFP) and multi-unit spike discharge rates (SDR) from the IC immediately after and one-week post-exposure. Measurements obtained immediately post-exposure demonstrated a significant reduction in supra-threshold CAP amplitudes. In contrast to the periphery, sound-evoked activity in the IC was enhanced in a frequency-dependent manner consistent with models of enhanced central gain. Surprisingly, one-week post-exposure supra-threshold responses from the cochlea had not only recovered, but were significantly larger than normal, and thresholds were significantly better than controls. Moreover, sound-evoked hyperactivity in the IC was sustained within the noise exposure frequency band but suppressed at higher frequencies. When response amplitudes representing the neural output of the cochlea and IC activity at one-week post exposure were compared with control animal responses, a central attenuation phenomenon becomes evident, which may play a key role in understanding why low-level noise can sometimes ameliorate tinnitus and hyperacusis percepts.

Assessment of Ipsilateral Efferent Effects in Human via ECochG.

Development of electrophysiological means to assess the medial olivocochlear (MOC) system in humans is important to further our understanding of the function of that system and for the refinement and validation of psychoacoustical and otoacoustic emission methods which are thought to probe the MOC. Based on measurements in anesthetized animals it has been hypothesized that the MOC-reflex (MOCR) can enhance the response to signals in noise, and several lines of evidence support such a role in humans. A difficulty in these studies is the isolation of efferent effects. Efferent activation can be triggered by acoustic stimulation of the contralateral or ipsilateral ear, but ipsilateral stimulation is thought to be more effective. However, ipsilateral stimulation complicates interpretation of effects since these sounds can affect the perception of other ipsilateral sounds by mechanisms not involving olivocochlear efferents. We assessed the ipsilaterally evoked MOCR in human using a transtympanic procedure to record mass-potentials from the cochlear promontory or the niche of the round window. Averaged compound action potential (CAP) responses to masked probe tones of 4 kHz with and without a precursor (designed to activate the MOCR but not the stapedius reflex) were extracted with a polarity alternating paradigm. The masker was either a simultaneous narrow band noise masker or a short (20-ms) tonal ON- or OFF-frequency forward masker. The subjects were screened for normal hearing (audiogram, tympanogram, threshold stapedius reflex) and psychoacoustically tested for the presence of a precursor effect. We observed a clear reduction of CAP amplitude by the precursor, for different masking conditions. Even without an MOCR, this is expected because the precursor will affect the response to subsequent stimuli via neural adaptation. To determine whether the precursor also activated the efferent system, we measured the CAP over a range of masker levels, with or without precursor, and for different types of masker. The results show CAP reduction consistent with the type of gain reduction caused by the MOCR. These results generally support psychoacoustical paradigms designed to probe the efferent system as indeed activating the MOCR system, but not all observations are consistent with this mechanism.

Delayed changes in auditory status in cochlear implant users with preserved acoustic hearing

This retrospective review explores delayed-onset hearing loss in 85 individuals receiving cochlear implants designed to preserve acoustic hearing at the University of Iowa Hospitals and Clinics between 2001 and 2015. Repeated measures of unaided behavioral audiometric thresholds, electrode impedance, and electrically evoked compound action potential (ECAP) amplitude growth functions were used to characterize longitudinal changes in auditory status. Participants were grouped into two primary categories according to changes in unaided behavioral thresholds: (1) stable hearing or symmetrical hearing loss and (2) delayed loss of hearing in the implanted ear. Thirty-eight percent of this sample presented with delayed-onset hearing loss of various degrees and rates of change. Neither array type nor insertion approach (round window or cochleostomy) had a significant effect on prevalence. Electrode impedance increased abruptly for many individuals exhibiting precipitous hearing loss; the increase was often transient. The impedance increases were significantly larger than the impedance changes observed for individuals with stable or symmetrical hearing loss. Moreover, the impedance changes were associated with changes in behavioral thresholds for individuals with a precipitous drop in behavioral thresholds. These findings suggest a change in the electrode environment coincident with the change in auditory status. Changes in ECAP thresholds, growth function slopes, and suprathreshold amplitudes were not correlated with changes in behavioral thresholds, suggesting that neural responsiveness in the region excited by the implant is relatively stable. Further exploration into etiology of delayed-onset hearing loss post implantation is needed, with particular interest in mechanisms associated with changes in the intracochlear environment.

Outer Hair Cell and Auditory Nerve Function in Speech Recognition in Quiet and in Background Noise.

The goal of this study was to describe the contribution of outer hair cells (OHCs) and the auditory nerve (AN) to speech understanding in quiet and in the presence of background noise. Fifty-three human subjects with hearing ranging from normal to moderate sensorineural hearing loss were assayed for both speech in quiet (Word Recognition) and speech in noise (QuickSIN test) performance. Their scores were correlated with OHC function as assessed via distortion product otoacoustic emissions, and AN function as measured by amplitude, latency, and threshold of the VIIIth cranial nerve Compound Action Potential (CAP) recorded during electrocochleography (ECochG). Speech and ECochG stimuli were presented at equivalent sensation levels in order to control for the degree of hearing sensitivity across patients. The results indicated that (1) OHC dysfunction was evident in the lower range of normal audiometric thresholds, which demonstrates that OHC damage can produce “Hidden Hearing Loss,” (2) AN dysfunction was evident beginning at mild levels of hearing loss, (3) when controlled for normal OHC function, persons exhibiting either high or low ECochG amplitudes exhibited no statistically significant differences in neither speech in quiet nor speech in noise performance, (4) speech in noise performance was correlated with OHC function, (5) hearing impaired subjects with OHC dysfunction exhibited better speech in quiet performance at or near threshold when stimuli were presented at equivalent sensation levels. These results show that OHC dysfunction contributes to hidden hearing loss, OHC function is required for optimum speech in noise performance, and those persons with sensorineural hearing loss exhibit better word discrimination in quiet at or near their audiometric thresholds than normal listeners.

Contralateral Inhibition of Click- and Chirp-Evoked Human Compound Action Potentials.

Cochlear outer hair cells (OHC) receive direct efferent feedback from the caudal auditory brainstem via the medial olivocochlear (MOC) bundle. This circuit provides the neural substrate for the MOC reflex, which inhibits cochlear amplifier gain and is believed to play a role in listening in noise and protection from acoustic overexposure. The human MOC reflex has been studied extensively using otoacoustic emissions (OAE) paradigms; however, these measurements are insensitive to subsequent “downstream” efferent effects on the neural ensembles that mediate hearing. In this experiment, click- and chirp-evoked auditory nerve compound action potential (CAP) amplitudes were measured electrocochleographically from the human eardrum without and with MOC reflex activation elicited by contralateral broadband noise. We hypothesized that the chirp would be a more optimal stimulus for measuring neural MOC effects because it synchronizes excitation along the entire length of the basilar membrane and thus evokes a more robust CAP than a click at low to moderate stimulus levels. Chirps produced larger CAPs than clicks at all stimulus intensities (50–80 dB ppeSPL). MOC reflex inhibition of CAPs was larger for chirps than clicks at low stimulus levels when quantified both in terms of amplitude reduction and effective attenuation. Effective attenuation was larger for chirp- and click-evoked CAPs than for click-evoked OAEs measured from the same subjects. Our results suggest that the chirp is an optimal stimulus for evoking CAPs at low stimulus intensities and for assessing MOC reflex effects on the auditory nerve. Further, our work supports previous findings that MOC reflex effects at the level of the auditory nerve are underestimated by measures of OAE inhibition.