Compound Action Potential Amplitude Research Articles

Ex-vivo systems for neuromodulation: A comparison of ex-vivo and in-vivo large animal nerve electrophysiology

BackgroundLittle research exists on extending ex-vivo systems to large animal nerves, and to the best of our knowledge, there has yet to be a study comparing these against in-vivo data. This paper details the first ex-vivo system for large animal peripheral nerves to be compared with in-vivo results. New MethodDetailed ex-vivo and in-vivo closed-loop neuromodulation experiments were conducted on pig ulnar nerves. Temperatures from 20 °C to 37 °C were evaluated for the ex-vivo system. The data were analysed in the time and velocity domains, and a regression analysis established how evoked compound action potential amplitude and modal conduction velocity (CV) varied with temperature and time after explantation. Main resultsPig ulnar nerves were sustained ex-vivo up to 5 h post-explantation. CV distributions of ex-vivo and in-vivo data were compared, showing closer correspondence at 37 °C. Regression analysis results also demonstrated that modal CV and time since explantation were negatively correlated, whereas modal CV and temperature were positively correlated. Comparison with Existing MethodsPrevious ex-vivo systems were primarily aimed at small animal nerves, and we are not aware of an ex-vivo system to be directly compared with in-vivo data. This new approach provides a route to understand how ex-vivo systems for large animal nerves can be developed and compared with in-vivo data. ConclusionThe proposed ex-vivo system results were compared with those seen in-vivo, providing new insights into large animal nerve activity post-explantation. Such a system is crucial for complementing in-vivo experiments, maximising collected experimental data, and accelerating neural interface development.

Inhibition of compound action potentials in the frog sciatic nerve by inchinkoto, a traditional Japanese medicine used for oral mucositis

ObjectiveThis study aimed to determine the effects of traditional Japanese (Kampo) medicines used to treat oral mucositis on nerve conduction. MethodsThe effects of Kampo medicines, crude drugs, and chemical compounds on compound action potentials (CAPs) were analyzed using extracellular recordings in frog sciatic nerves. ResultsAmong the Kampo medicines, inchinkoto demonstrated the most significant reduction in CAP amplitude, with a half-maximal inhibitory concentration (IC50) of 5.4 mg/mL. Hangeshashinto, shosaikoto, hochuekkito, and juzentaihoto also showed a significant reduction. Regarding inchinkoto, Artemisiae Capillari Spica (artemisia) was the most effective crude drug, with an IC50 of 4.2 mg/mL for CAP amplitude reduction, whereas Gardeniae Fructus (gardenia) exerted no significant effect. However, the combined use of artemisia and gardenia reduced the CAP amplitude more effectively than artemisia alone, indicating a synergistic interaction. The chemical ingredient eugenol from artemisia administered at 1 and 3 mmol/L reduced CAP amplitude, whereas other chemical ingredients administered at 0.1 and 1 mmol/L had no significant effects. ConclusionsInchinkoto exhibited the most effective reduction in CAP amplitude in the sciatic nerve of frogs, primarily through the action of artemisia, with potential synergistic interaction between artemisia and gardenia.

Personalized inference for neurostimulation with meta-learning: a case study of vagus nerve stimulation.

Objective. Neurostimulation is emerging as treatment for several diseases of the brain and peripheral organs. Due to variability arising from placement of stimulation devices, underlying neuroanatomy and physiological responses to stimulation, it is essential that neurostimulation protocols are personalized to maximize efficacy and safety. Building such personalized protocols would benefit from accumulated information in increasingly large datasets of other individuals' responses.Approach. To address that need, we propose a meta-learning family of algorithms to conduct few-shot optimization of key fitting parameters of physiological and neural responses in new individuals. While our method is agnostic to neurostimulation setting, here we demonstrate its effectiveness on the problem of physiological modeling of fiber recruitment during vagus nerve stimulation (VNS). Using data from acute VNS experiments, the mapping between amplitudes of stimulus-evoked compound action potentials (eCAPs) and physiological responses, such as heart rate and breathing interval modulation, is inferred.Main results. Using additional synthetic data sets to complement experimental results, we demonstrate that our meta-learning framework is capable of directly modeling the physiology-eCAP relationship for individual subjects with much fewer individually queried data points than standard methods.Significance. Our meta-learning framework is general and can be adapted to many input-response neurostimulation mapping problems. Moreover, this method leverages information from growing data sets of past patients, as a treatment is deployed. It can also be combined with several model types, including regression, Gaussian processes with Bayesian optimization, and beyond.

Acoustically Evoked Compound Action Potentials Recorded From Cochlear Implant Users With Preserved Acoustic Hearing.

Less traumatic intracochlear electrode design and the introduction of the soft surgery technique allow for the preservation of low-frequency acoustic hearing in many cochlear implant (CI) users. Recently, new electrophysiologic methods have also been developed that allow acoustically evoked peripheral responses to be measured in vivo from an intracochlear electrode. These recordings provide clues to the status of peripheral auditory structures. Unfortunately, responses generated from the auditory nerve (auditory nerve neurophonic [ANN]) are somewhat difficult to record because they are smaller than the hair cell responses (cochlear microphonic). Additionally, it is difficult to completely segregate the ANN from the cochlear microphonic, complicating the interpretation and limiting clinical applications. The compound action potential (CAP) is a synchronous response of multiple auditory nerve fibers and may provide an alternative to ANN where the status of the auditory nerve is of primary interest. This study is a within-subject comparison of CAPs recorded using traditional stimuli (clicks and 500 Hz tone bursts) and a new stimulus (CAP chirp). We hypothesized that the chirp stimulus might result in a more robust CAP than that recorded using traditional stimuli, allowing for a more accurate assessment of the status of the auditory nerve. Nineteen adult Nucleus L24 Hybrid CI users with residual low-frequency hearing participated in this study. CAP responses were recorded from the most apical intracochlear electrode using a 100 μs click, 500 Hz tone bursts, and chirp stimuli presented via the insert phone to the implanted ear. The chirp stimulus used in this study was CAP chirp generated using parameters from human-derived band CAPs ( Chertoff et al. 2010 ). Additionally, nine custom chirps were created by systematically varying the frequency sweep rate of the power function used to construct the standard CAP chirp stimulus. CAPs were recorded using all acoustic stimuli, allowing for within-subject comparisons of the CAP amplitude, threshold, percentage of measurable CAP responses, and waveform morphology. Considerable variation in response morphology was apparent across stimuli and stimulation levels. Clicks and CAP chirp significantly evoked identifiable CAP response more compared to 500 Hz tone bursts. At relatively high stimulation levels, the chirp-evoked CAPs were significantly larger in amplitude and less ambiguous in morphology than the click-evoked CAPs. The status of residual acoustic hearing at high frequencies influenced the likelihood that a CAP could be reliably recorded. Subjects with better preserved hearing at high frequencies had significantly larger CAP amplitudes when CAP chirp was used. Customizing the chirp stimulus by varying the frequency sweep rates significantly affected the CAP amplitudes; however, pairwise comparisons did not show significant differences between chirps. CAPs can be measured more effectively using broadband acoustic stimuli than 500 Hz tone bursts in CI users with residual low-frequency acoustic hearing. The advantage of using CAP chirp stimulus relative to standard clicks is dependent on the extent of preserved acoustic hearing at high frequencies and the stimulus level. The chirp stimulus may present an attractive alternative to standard clicks or tone bursts for this CI population when the goal is to record robust CAP responses.

Supercharge End-to-Side Motor Transfer to a Long Nerve Graft to Enhance Motor Regeneration: An Experimental Rat Study.

Long nerve grafts are prone to chronic denervation, often resulting in unsatisfactory clinical outcomes. The authors aim to investigate whether supercharge end-to-side (SETS) motor nerve transfers to a long nerve graft can potentially enhance nerve regeneration and functional outcomes. A reversed long nerve graft was interposed between the C6 and the musculocutaneous nerve in 48 rats. The motor nerves near the C6 proximally and the musculocutaneous nerve distally were chosen for SETS transfer to the long nerve graft. There were four groups: (A) nerve graft only, (B) proximal SETS transfer, (C) distal SETS transfer, and (D) proximal and distal double SETS transfers. A grooming test was assessed at 4, 8, 12, and 16 weeks postoperatively. Biceps weight, compound muscle action potential amplitude, tetanic contraction force, and histomorphometric analysis of the musculocutaneous nerve were evaluated at 16 weeks. Long nerve grafts that received SETS transfers (groups B, C, and D) showed superior results compared with the control group. Proximal SETS transfer had significantly better outcomes than distal SETS transfer in electrodiagnostic parameters, whereas double SETS transfer had the highest axonal count and biceps compound muscle action potential amplitude. SETS motor transfers to long nerve grafts can effectively improve functional outcome and optimize nerve graft regeneration to the target nerve. Long nerve grafts yield suboptimal functional results. The experimental study showed that SETS motor transfer to a long nerve graft improves muscle functional outcomes. A double motor SETS transfer provides the best results. Proximal SETS transfer might have more benefits over distal transfer.

In Vivo Efficacy of a Novel, Sutureless Coaptation Device for Repairing Peripheral Nerve Defects.

Although microsuture neurorrhaphy is the accepted clinical standard treatment for severed peripheral nerves, this technique requires microsurgical proficiency and still often fails to provide adequate nerve approximation for effective regeneration. Entubulation utilizing commercially available conduits may enhance the technical quality of the nerve coaptation and potentially provide a proregenerative microenvironment, but still requires precise suture placement. We developed a sutureless nerve coaptation device, Nerve Tape®, that utilizes Nitinol microhooks embedded within a porcine small intestinal submucosa backing. These tiny microhooks engage the outer epineurium of the nerve, while the backing wraps the coaptation to provide a stable, entubulated repair. In this study, we examine the impact of Nerve Tape on nerve tissue and axonal regeneration, compared with repairs performed with commercially available conduit-assisted or microsuture-only repairs. Eighteen male New Zealand white rabbits underwent a tibial nerve transection, immediately repaired with (1) Nerve Tape, (2) conduit plus anchoring sutures, or (3) four 9-0 nylon epineurial microsutures. At 16 weeks postinjury, the nerves were re-exposed to test sensory and motor nerve conduction, measure target muscle weight and girth, and perform nerve tissue histology. Nerve conduction velocities in the Nerve Tape group were significantly better than both the microsuture and conduit groups, while nerve compound action potential amplitudes in the Nerve Tape group were significantly better than the conduit group only. Gross morphology, muscle characteristics, and axon histomorphometry were not statistically different between the three repair groups. In the rabbit tibial nerve repair model, Nerve Tape offers similar regeneration efficacy compared with conduit-assisted and microsuture-only repairs, suggesting minimal impact of microhooks on nerve tissue.

ANXIETY AND DEPRESSION IN TYPE 2 DIABETES MELLITUS: A STUDY INCLUDING NERVE CONDUCTION STUDY AND NEUROPATHIC PAIN

Objective: It is known that neuropathy, neuropathic pain and psychiatric disorders are associated with diabetes mellitus (DM). It was aimed to find out whether there is a relationship between nerve conduction study findings, neuropathic pain, depression and anxiety.
 
 Material and Methods: Type 2 DM patients that applied to our clinical neurophysiology laboratory between September 2021 and January 2022 were included in this study. Median, ulnar, sural, peroneal and posterior tibial nerve conduction studies were performed on the patients. Douleur Neuropathique 4 Questions (DN4) was applied to the patients to evaluate neuropathic pain. Hospital Anxiety and Depression Scale (HADS) was applied to the patients. Anxiety (HADS-A) and depression (HADS-S) scores, which are the two subsections of HADS, were included in the analysis.
 
 Results: Forty DM patients (27 males, 13 females) were included in the study. The mean age of the patients was 57.9±12.7 (min-max 23-83) years. The number of patients with neuropathic pain, polyneuropathy according to neurophysiological findings, abnormal HADS-A and HADS-D scores were 32 (80%), 23 (58%), 17 (43%), and 24 (60%), respectively. Neuropathic pain was present in 22 (96%) and 10 (59%) of the patients with and without polyneuropathy, respectively. Neuropathic pain was found in 22 (92%) patients with depression and 16 (63%) patients without depression (p=0.046). Among patients with neuropathic pain, compound nerve action potential amplitudes of median, ulnar and sural nerves were lower than those without neuropathic pain (p=0.011, p=0.027, p

Intraoperative Electrically Evoked Compound Action Potential Growth and Maximum Amplitudes in Hearing Preservation Cochlear Implant Recipients.

Electrically evoked compound action potentials (eCAPs) obtained from cochlear implant (CI) recipients reflect responsiveness of the auditory nerve to electrical stimulation. The recent use of atraumatic electrode arrays and expansion of CI candidacy to listeners with greater residual hearing may lead to increased clinical utility of intraoperative eCAP recordings. To examine the effect of electrode array (slim modiolar versus slim straight) on suprathreshold intraoperative eCAP recordings in hearing preservation CI recipients. A secondary goal was to examine potential clinical applications of intraoperative eCAPs for predicting immediate hearing preservation and speech perception outcomes. Retrospective study of 113 adult hearing preservation CI candidates implanted from 2015 to 2019 with either a slim modiolar or slim straight electrode array. Intraoperative eCAP growth functions and maximum amplitudes were obtained at several intracochlear electrodes and examined as a function of implanted array and hearing preservation status, while controlling for electrode impedance. From basal to apical electrodes, progressively larger eCAP amplitudes and steeper slopes were recorded. Steeper eCAP slopes at apical electrodes were also seen for recipients of the slim modiolar array (versus slim straight). Suprathreshold eCAP responses did not differ as a function of hearing preservation and were not associated with speech recognition. More robust eCAP responses were obtained from apical electrodes, which is consistent with better low-frequency thresholds in hearing preservation recipients. This effect was compounded by type of electrode array. Results also suggest that intraoperative, suprathreshold eCAPs cannot be used to predict the success of hearing preservation surgery or performance with the CI.

Minimum Detectable Differences in Electrocochleography Measurements: Bayesian-Based Predictions.

Physiology of the cochlea and auditory nerve can be assessed with electrocochleography (ECochG), a technique that involves measuring auditory evoked potentials from an electrode placed near or within the cochlea. Research, clinical, and operating room applications of ECochG have in part centered on measuring the auditory nerve compound action potential (AP) amplitude, the summating potential (SP) amplitude, and the ratio of the two (SP/AP). Despite the common use of ECochG, the variability of repeated amplitude measurements for individuals and groups is not well understood. We analyzed ECochG measurements made with a tympanic membrane electrode in a group of younger normal-hearing participants to characterize the within-participant and group-level variability for the AP amplitude, SP amplitude, and SP/AP amplitude ratio. Results show that the measurements have substantial variability and that, especially with smaller sample sizes, significant reduction in variability can be obtained by averaging measurements across repeated electrode placements within subjects. Using a Bayesian-based model of the data, we generated simulated data to predict minimum detectable differences in AP and SP amplitudes for experiments with a given number of participants and repeated measurements. Our findings provide evidence-based recommendations for the design and sample size determination of future experiments using ECochG amplitude measurements, and the evaluation of previous publications in terms of sensitivity to detecting experimental effects on ECochG amplitude measurements. Accounting for the variability of ECochG measurements should result in more consistent results in the clinical and basic assessments of hearing and hearing loss, either hidden or overt.

Corticospinal and spinal adaptations following lower limb motor skill training: a meta-analysis with best evidence synthesis.

Motor skill training alters the human nervous system; however, lower limb motor tasks have been less researched compared to upper limb tasks. This meta-analysis with best evidence synthesis aimed to determine the cortical and subcortical responses that occur following lower limb motor skill training, and whether these responses are accompanied by improvements in motor performance. Following a literature search that adhered to the PRISMA guidelines, data were extracted and analysed from six studies (n = 172) for the meta-analysis, and 11 studies (n = 257) were assessed for the best evidence synthesis. Pooled data indicated that lower limb motor skill training increased motor performance, with a standardised mean difference (SMD) of 1.09 being observed. However, lower limb motor skill training had no effect on corticospinal excitability (CSE), Hoffmann's reflex (H-reflex) ormuscle compound action potential (MMAX)amplitude. The best evidence synthesis found strong evidence for improved motor performance and reduced short-interval cortical inhibition (SICI) following lower limb motor skill training, with conflicting evidence towards the modulation of CSE. Taken together, this review highlights the need for further investigation on how motor skill training performed with the lower limb musculature canmodulate corticospinal responses. This will also help us to better understand whether these neuronal measures are underpinning mechanisms that support an improvement in motor performance.

An invertebrate model in examining the effect of acute ferric iron exposure on proprioceptive neurons

Iron is an essential element for plant and animal life and is found in soil, fresh waters and marine waters. The Fe3+ ion is a vital prosthetic group and cofactor to mitochondrial electron transport complexes and numerous proteins involved in normal functioning. Despite its importance to life-sustaining processes, overexposure results in toxicity. For example, ferric iron (Fe3+) accumulation in the mammalian central nervous system is associated with various neurological disorders. Although current literature addresses the long-term effects of Fe3+ overload, fewer studies exist examining the effects of acute exposure. Using the blue crab (Callinectes sapidus), we investigate the effects of acute Fe3+ overload on proprioception within the propodite-dactylopodite (PD) nerve. For proprioceptive studies, 10- and 20-mM ferric chloride and ferric ammonium citrate solutions were used at 5- and 20- min exposure times. Exposure to 20 mM concentrations of ferric chloride and ferric ammonium citrate reduced excitability in proprioceptive neurons. Thus, Fe3+ likely blocks stretch-activated channels or voltage-gated Na+ channels. The depressive effects of Fe3+ are partly reversible following saline washout, indicating cells are not acutely damaged. Gadolinium (GdCl3, 1 and 10 mM) was used to examine the effects of an additional trivalent ion comparator. Gd3+ depressed PD nerve compound action potential amplitude while increasing the compound action potential duration. This study is relevant in demonstrating the dose-dependent effects of acute Fe3+ and Gd3+ exposure on proprioception and provides a model system to further investigate the mechanisms by which metals act on the nervous system.

Astaxanthin-folic acid combined treatment potentiates neuronal regeneration and functional recovery after brachial plexus avulsion and reimplantation.

Brachial plexus avulsion (BPA), which commonly occurs in neonatal birth injuries and car accidents, severely disrupts spinal cord segments and nerve roots. Avulsion is usually located in the transitional zone at the junction of spinal nerve roots and starting point of the spinal cord, which places heavy disability burdens on patients due to sensory and motor function loss in the innervated areas. Primary mechanical injuries and secondary pathogenesis, such as inflammatory infiltration and oxidative stress, lead to inefficient management and poor prognosis. Astaxanthin (AST) has a strong ability to bleach singlet oxygen and capture free radicals, quench singlet oxygen and trap free radicals, and folic acid (FC) can effectively inhibit the inflammatory response. This study aimed to investigate the therapeutic effects of AST and FC on BPA. The 24 h after BPA was considered the acute phase of the injury, and the combination of AST and FC had the best therapeutic effect due to the synergistic effect of AST’s antioxidant and FC’s anti-inflammatory properties. At 6 weeks after BPA, AST-FC promoted the recovery of biceps motor functions, increased myofiber diameter, enlarged the amplitude of musculocutaneous nerve-biceps compound action potential, and improved Terzis grooming test (TGT) scores. Meanwhile, more functional ventral horn motor neurons in the spinal cord were maintained. In conclusion, AST-FC combined therapy has a potential role in the clinical management of BPA since it can effectively alleviate oxidative stress and the inflammatory response in the acute phase of BPA, increase the survival rate of neurons, and promote neuronal regeneration and recovery of motor functions in the late stage of BPA.

The effect of stretching on nerve excitability

Nerves are frequently stretched during movement. We investigate here the effect of stretch on nerve excitability within the framework of the soliton theory. This thermodynamic theory for nerve pulse propagation relies on the presence of a melting transition in the nerve membrane. In this transition, the area of the nerve membrane and the nerve thickness change. It depends on thermodynamic variables including temperature, the chemical potentials of anesthetics and on hydrostatic pressure. A further variable relevant for movement science is the the stretching of nerves, i.e., a tension in the nerve caused by muscle contraction, the bending of joints and the pulling on extremities. We show here that the soliton theory predicts a decrease in nerve excitability upon stretching. This becomes evident in a reduction of the amplitude of compound action potentials and in the suppression of reflexes. We compare these predictions with medical findings.

Mother and sibling interactions during the preweaning period influence myelination and impulse propagation of the sensory sural nerve in the adult rat.

To investigate whether mother and sibling interactions during the preweaning period influence the histological and electrophysiological characteristics of the sensory sural nerve (SUn) in the adult rat, litters composed of 1, 3, 6, 9, and 12 male pups (P) were formed and the pups routinely weighed until postnatal day 60 (PND60). At PND9, 3P and 6P litters showed greater body weight than pups without siblings or from 9P or 12P litters, and such differences in weight were maintained until adulthood. Analysis of maternal licking at PND8 and 9 showed that pups from large litters received fewer licks than pups from small size litters. At PND60, SUn of rats from 6P and 9P litters had greater compound action potential (CAP) amplitude and a higher proportion of axons with large myelin thickness than nerves from rats of 1P, 3P, or 12P litters. SUn of heaviest rats from 9P and 12P litters had greater CAP area and myelination than the lightest rats from the same litters. We propose that a complex interplay of sensory, social, and nutritional factors arising from mother and littermate interactions during the preweaning period influence myelination and the propagation of action potentials in the SUn of adult rats.

Preparation of Rat Sciatic Nerve for Ex Vivo Neurophysiology.

Ex vivo preparations enable the study of many neurophysiological processes in isolation from the rest of the body while preserving local tissue structure. This work describes the preparation of rat sciatic nerves for ex vivo neurophysiology, including buffer preparation, animal procedures, equipment setup and neurophysiological recording. This work provides an overview of the different types of experiments possible with this method. The outlined method aims to provide 6 h of stimulation and recording on extracted peripheral nerve tissue in tightly controlled conditions for optimal consistency in results. Results obtained using this method are A-fibre compound action potentials (CAP) with peak-to-peak amplitudes in the millivolt range over the entire duration of the experiment. CAP amplitudes and shapes are consistent and reliable, making them useful to test and compare new electrodes to existing models, or the effects of interventions on the tissue, such as the use of chemicals, surgical alterations, or neuromodulatory stimulation techniques. Both conventional commercially available cuff electrodes with platinum-iridium contacts and custom-made conductive elastomer electrodes were tested and gave similar results in terms of nerve stimulus strength-duration response.

Spironolactone Ameliorates Cochlear Implant Induced Endolymphatic Hydrops.

Endolymphatic hydrops (EH) has been observed in both animal and human cochleae following cochlear implant (CI) surgery. We tested whether EH could be eliminated by administration of mineralocorticoid steroid antagonist spironolactone and explored the electrophysiological consequences of this. Sixty-four adult guinea pigs underwent cochlear implantation with a dummy electrode. Animals then survived either 2, 7, or 28 days. Auditory function was monitored by recording electrocochleography from the round window membrane preimplantation, and on the last day of the experiment. Spironolactone or control solution was added to animals' feed for 7 days (if they survived that long) beginning immediately prior to surgery. The presence of EH was determined using thin-sheet laser imaging microscopy. Treatment with spironolactone resulted in significant reduction in EH in the second cochlear turn 7 days postimplantation. In all animals, the compound action potential (CAP) threshold was elevated 2 days postimplantation, but for most frequencies had recovered substantially by 28 days. There was no treatment effect on CAP thresholds. SP/AP ratios were elevated at day 2. The amplitude growth of the CAP did not differ between test and control groups at any time after implantation. EH can be suppressed by antagonism of mineralocorticoid receptors in the week after cochlear implantation. Reduction in EH did not lead to any change in hearing, and there was no indication of synaptopathy signalled by reduced CAP amplitude at high sound intensities. We found no electrophysiological evidence that EH early after implantation impacts negatively upon preservation of residual hearing.

Early Expression of MMP-9 Predicts Recovery of Tibialis Anterior after Sciatic Nerve Crush Injury.

Background:The purpose of this study was to assess the expression of molecular markers and epineural blood flow after differing degrees of nerve injury to identify potential tools to predict nerve recovery in a rat sciatic nerve model.Methods:A total of 72 rats were divided into nine groups. Each group was subjected to one of three crush injuries, created by applying one of three vascular clamps for 30 seconds. Vascularity was assessed with laser Doppler flowmetry before and after crush, and at nonsurvival surgery. Nonsurvival surgeries were performed 6 hours, 2 weeks, or 6 weeks later with nerve conduction studies and muscle strength testing. Expression of matrix metalloproteinase 9 (MMP-9) and matrix metalloproteinase 2 (MMP-2) in each nerve was quantified using with enzyme linked immunosorbent analysis.Results:Persistent hyperemia was noted in the zone of injury compared with baseline at 2 weeks and 6 weeks in the groups that displayed incomplete recovery. Expression of MMP-9 at 6 hours increased with increasing severity of crush and was inversely related to tibialis anterior muscle force recovery. The ratio of MMP-9:MMP-2 expression correlated well with recovery of compound nerve action potential amplitude at 6 weeks.Conclusions:Resolution of nerve hyperemia may correlate with nerve recovery from trauma, but early measures of nerve blood flow after injury are not prognostic of recovery. Ratio of MMP-9:MMP-2 expression 6 hours after injury correlates with recovery of compound nerve action potential at 6 weeks, while MMP-9 expression alone predicts tibialis anterior recovery. These findings together suggest that increased MMP-9 expression is a potentially useful marker of more severe nerve injury.

Simultaneous measurement of human auditory nerve and brainstem potentials: Effects of upward spread of excitation

Acoustic clicks evoke strong synchrony of auditory-nerve (AN) fibers, thereby eliciting a compound action potential (CAP); however, synchrony is reduced by the delay of the cochlear traveling wave. Upward-frequency chirps compensate for this delay, resulting in larger CAPs evoked by chirps than clicks. Our model simulations of CAPs suggest that chirps presented at high intensities (100 dB peSPL) adapt basal AN fibers via upward spread of excitation of low-frequency chirp components. This adaptation results in less-than-or-equal-to CAP amplitudes and distorted CAP morphology compared to CAPs evoked by clicks. Simulations show that these effects on CAP amplitude and morphology can be avoided by reducing the amplitude of the low-frequency components of the chirp (i.e., modified chirp). Here we present CAPs from 12 young adults with NH, which for high stimulus intensities, exhibit reduced amplitudes and broader CAP morphology for chirps than clicks, whereas CAP amplitudes for modified chirps exceed those for clicks, consistent with model simulations. The distorted CAP morphology in response to high-level chirps is consistent with adaptation of AN responses and broad cochlear excitation. Interestingly, the deleterious effects of high-level chirps on CAP amplitude and morphology are reduced or absent in simultaneous recordings of the auditory brainstem response.

Firing Rate Adaptation of the Human Auditory Nerve Optimizes Neural Signal-to-Noise Ratios.

Several physiological mechanisms act on the response of the auditory nerve (AN) during acoustic stimulation, resulting in an adjustment in auditory gain. These mechanisms include-but are not limited to-firing rate adaptation, dynamic range adaptation, the middle ear muscle reflex, and the medial olivocochlear reflex. A potential role of these mechanisms is to improve the neural signal-to-noise ratio (SNR) at the output of the AN in real time. This study tested the hypothesis that neural SNRs, inferred from non-invasive assessment of the human AN, improve over the duration of acoustic stimulation. Cochlear potentials were measured in response to a series of six high-level clicks embedded in a series of six lower-level broadband noise bursts. This paradigm elicited a compound action potential (CAP) in response to each click and to the onset of each noise burst. The ratio of CAP amplitudes elicited by each click and noise burst pair (i.e., neural SNR) was tracked over the six click/noise bursts. The main finding was a rapid (< 24ms) increase in neural SNR from the first to the second click/noise burst, consistent with a real-time adjustment in the response of the auditory periphery toward improving the SNR of the signal transmitted to the brainstem. Analysis of cochlear microphonic and ear canal sound pressure recordings, as well as the time course for this improvement in neural SNR, supports the conclusion that firing rate adaptation is likely the primary mechanism responsible for improving neural SNR, while dynamic range adaptation, the middle ear muscle reflex, and the medial olivocochlear reflex played a secondary role on the effects observed in this study. Real-time improvements in neural SNR are significant because they may be essential for robust encoding of speech and other relevant stimuli in the presence of background noise.

Surgical Procedures Required for Measurement Reduce Nerve Conduction Velocity: An In Vivo and In Vitro Comparative Study

Background: Although in vitro methods have disadvantages, they are still commonly used to measure nerve conduction velocity (NCV) in experimental studies. Therefore, this study was designed to demonstrate the effect of the surgical procedures required for in vitro methods on nerve fibers and the effect of in vivo and in vitro methods on the results of electrophysiological measurements. Methods: Rats were assigned to the in vivo (control-1, injury-1, and diabetic-1) and in vitro (control-2, injury-2, and diabetic-2) groups. The NCV and compound action potential amplitudes were measured, and the nerve fibers were histologically examined. Results: Damaged axons and myelin sheaths were observed in the control-2 group. The electrophysiological values of the in vitro groups were lower than those of the in vivo groups. Furthermore, these values were lower for the diabetic and injury groups than for the control groups. Conclusions: This study showed that the surgical procedures required for the in vitro method reduced the measured values. Owing to the previous and current disadvantages of the in vitro method, the in vivo method was more sensitive for the NCV measurement. Moreover, measurements can be performed using the current in vivo method for small nerve fibers.