Implantation of the lateral cochlear wall for auditory nerve stimulation

Although cochlear implants now regularly achieve gratifying results, traditional intrascalar implants have certain limitations. Extraluminal implants may offset some of these problems by accessing neurons subserving a wider tonotopic range, avoiding intracochlear insertion trauma, and offering alternatives when cochlear obliteration is present. We have investigated the utility of a lateral cochlear wall implant in a normal-hearing cat model with implants at the middle and basal turns, and found successful activation of the auditory nerve at thresholds of 28.1 and 40.6 microA, respectively. No adventitial stimulation of the facial nerve was noted within the dynamic range. Maximum responsiveness was observed with implants of the middle turn of the cochlea, an area that is not reliably approached with current intrascalar implants. These observations support and extend prior observations of the feasibility of extraluminal stimulation of the auditory nerve.     

Response of the primary auditory cortex to electrical stimulation of the auditory nerve in the congenitally deaf white cat

Neural activity plays an important role in the development and maintenance of sensory pathways. However, while there is considerable experience using cochlear implants in both congenitally deaf adults and children, little is known of the effects of a hearing loss on the development of the auditory cortex. In the present study, cortical evoked potentials, field potentials, and multi- and single-unit activity evoked by electrical stimulation of the auditory nerve were used to study the functional organisation of the auditory cortex in the adult congenitally deaf white cat. The absence of click-evoked auditory brainstem responses during the first weeks of life demonstrated that these animals had no auditory experience. Under barbiturate anaesthesia, cortical potentials could be recorded from the contralateral auditory cortex in response to bipolar electrical stimulation of the cochlea in spite of total auditory deprivation. Threshold, morphology and latency of the evoked potentials varied with the location of the recording electrode, with response latency varying from 10 to 20 ms. There was evidence of threshold shifts with site of the cochlear stimulation in accordance with the known cochleotopic organisation of AI. Thresholds also varied with the configuration of the stimulating electrodes in accordance with changes previously observed in normal hearing animals. Single-unit recordings exhibited properties similar to the evoked potentials. Increasing stimulus intensity resulted in an increase in spike rate and a decrease in latency to a minimum of approximately 8 ms, consistent with latencies recorded in AI of previously normal animals (Raggio and Schreiner, 1994). Single-unit thresholds also varied with the configuration of the stimulating electrodes. Strongly driven responses were followed by a suppression of spontaneous activity. Even at saturation intensities the degree of synchronisation was less than observed when recording from auditory brainstem nuclei. Taken together, in these auditory deprived animals basic response properties of the auditory cortex of the congenitally deaf white cat appear similar to those reported in normal hearing animals in response to electrical stimulation of the auditory nerve. In addition, it seems that the auditory cortex retains at least some rudimentary level of cochleotopic organisation.     

Pseudospontaneous activity: stochastic independence of auditory nerve fibers with electrical stimulation

We describe a novel signal processing strategy for cochlear implants designed to emphasize stochastic independence across the excited neural population. The strategy is based on the observation that high rate pulse trains may produce random spike patterns in auditory nerve fibers that are statistically similar to those produced by spontaneous activity in the normal cochlea. We call this activity 'pseudospontaneous'. A supercomputer-based computational model of a population of auditory nerve fibers suggests that different average rates of pseudospontaneous activity can be created by varying the stimulus current of a fixed-amplitude, high-rate pulse train, e.g. 5000 pps. Electrically-evoked compound action potentials recorded in a human cochlear implant subject are consistent with the hypothesis that such a stimulus can desynchronize the fiber population. This desynchronization may enhance neural representation of temporal detail and dynamic range with a cochlear implant and eliminate a major difference between acoustic and electric hearing.     

Middle latency responses to electrical stimulation of the auditory nerve in unanaesthetized guinea pigs

Middle latency responses (MLR) to sinusoidal and pulsatile electrical stimulation (ES) of the cochlea and to acoustical stimulation (AS) were evaluated in awake guinea pigs with chronically implanted electrodes. The ear, which was later electrically stimulated, was deafened by local intracochlear application of gentamicin, the opposite ear was left intact. Waveforms and P1-P2 interpeak intervals of the electrically evoked MLR (ES-MLR) were similar to those evoked by acoustical stimulation of the intact ear (AS-MLR) and the latencies of the ES-MLR were shorter by about 1-3 ms. Thresholds of ES-MLR in the frequency range 0.5-32 kHz increased with increasing ES frequency (slope 3.2 dB/octave), thresholds were 3.5-9.5 dB lower for intracochlear than for extracochlear ES. Dynamic ranges for ES-MLR varied between 6-20 dB. MLR amplitude-intensity functions for ES were steeper (slope 2-12 microV/dB) than those for AS (slope 0.2-2 microV/dB). Maximal ES-MLR amplitudes exceeded usually 1.5-3 times the amplitudes of the acoustically evoked MLR. Both types of stimulations evoked larger MLR amplitudes to contralateral stimulation than to ipsilateral stimulation (average ratio = 4.1 +/- 2.2 for AS and 3.3 +/- 2.2 for ES). Because of the relatively long latency and therefore insensitivity to electrical artifact, the ES-MLR can be used for the evaluation of different strategies of the electrical stimulation of the cochlea in awake guinea pig.     

Cumulation of the tendency to segregate auditory streams: resetting by changes in location and loudness

In four experiments, the accumulation, over time, of a tendency to hear separate high and low streams in a sequence of high (H) and low (L) tones, presented in a galloping rhythm (HLH-HLH-...), was studied. Each trial was composed of two parts, an induction sequence, then a test sequence, with no break between them. The test sequence was always heard at the far left. When the induction sequence and the test sequence were identical, the presence of the induction sequence increased the tendency for the test sequence to split into two streams. However, when the sequences differed in location (cued by differences in interaural timing or intensity over headphones and by loudspeaker placement in a free field) or when they differed in loudness, the accumulation of the segregative tendency was reset, and the test sequence sounded more integrated. When the induction sequence changed in location or loudness in gradual steps toward the value of the test sequence, resetting was much less. It appears that the accumulation of information about streams in different frequency regions is sensitive to sudden changes in parameters, even when they affect the frequency regions equally. This prevents the system from accumulating data across unrelated events.     

"Recalibrating" the auditory system: The perception of loudness.

Listening to relatively intense tones at one frequency and weak tones at another makes the latter relatively louder. The auditory system's relative response to low-frequency (f?) and high-frequency (f?) tones depends on the separation between f? and f?. When f? and f? differ little, loudness matches change little with shifts in mean sound pressure levels (SPLs) at each frequency; but when f? and f? differ more, matches change markedly, showing how the auditory system "recalibrates" its responses to f? and f?. The magnitude of recalibration and its frequency bandwidth also depend to a modest degree on the range of SPLs, their mean level, and the experimental paradigm. The representation of loudness reflects the processing and recalibration of multidimensional peripheral inputs within a higher level, context-sensitive (adaptation-like) mechanism. Other perceptual modalities show evidence of analogous mechanisms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Electrical stimulation of the auditory nerve. I. Correlation of physiological responses with cochlear status

The purpose of the present study was to evaluate evoked potential and single fibre responses to biphasic current pulses in animals with varying degrees of cochlear pathology, and to correlate any differences in the physiological response with status of the auditory nerve. Six cats, whose cochleae ranged from normal to a severe neural loss (< 5% spiral ganglion survival), were used. Morphology of the electrically evoked auditory brainstem response (EABR) was similar across all animals, although electrophonic responses were only observed from the normal animal. In animals with extensive neural pathology, EABR thresholds were elevated and response amplitudes throughout the dynamic range were moderately reduced. Analysis of single VIIIth nerve fibre responses were based on 207 neurons. Spontaneous discharge rates among fibres depended on hearing status, with the majority of fibres recorded from deafened animals exhibiting little or no spontaneous activity. Electrical stimulation produced a monotonic increase in discharge rate, and a systematic reduction in response latency and temporal jitter as a function of stimulus intensity for all fibres examined. Short-duration current pulses elicited a highly synchronous response (latency < 0.7 ms), with a less well synchronized response sometimes present (0.7-1.1 ms). There were, however, a number of significant differences between responses from normal and deafened cochleae. Electrophonic activity was only present in recordings from the normal animal, while mean threshold, dynamic range and latency of the direct electrical response varied with cochlear pathology. Differences in the ability of fibres to follow high stimulation rates were also observed; while neurons from the normal cochlea were capable of 100% entrainment at high rates (600-800 pulses per second (pps)), fibres recorded from deafened animals were often not capable of such entrainment at rates above 400 pps. Finally, a number of fibres in deafened animals showed evidence of 'bursting', in which responses rapidly alternated between high entrainment and periods of complete inactivity. This bursting pattern was presumably associated with degenerating auditory nerve fibres, since it was not recorded from the normal animal. The present study has shown that the pathological response of the cochlea following a sensorineural hearing loss can lead to a number of significant changes in the patterns of neural activity evoked via electrical stimulation. Knowledge of the extent of these changes have important implications for the clinical application of cochlear implants.     

Electric nerve stimulation (ENS): 70 clinical cases of bi-block aided by an electric bipolar signal

The paper describes medical informatics discipline and deals with decision support systems in more details. It describes the process of decision making using diagnostic and therapeutic decision making cycle and two sources of medical knowledge-scientific and empirical knowledge. It shows different approaches for development of computer supported decision systems and presents some examples of their use in medical practice.     

Transcutaneous electric nerve stimulation: a therapy that promises help in chronic pain

An 84-year-old patient with heparin-induced thrombocytopenia (HIT), global cardiac decompensation, and acute renal failure underwent a cardiosurgical intervention using an extracorporeal circuit. For systemic anticoagulation danaparoid (Orgaran) was applied as a heparin substitute preoperatively and maintained for systemic anticoagulation during ECC despite it being eliminated by the kidney. The postoperative recovery was prolonged due to bleeding complications. During cardiopulmonary bypass (216 min) the target level of anti-factor Xa was 1.5 UI/ml. This required continuous infusion and an occasional bolus of danaparoid. Coagulation in the extracorporeal circuit was observed twice at plasma levels below 1.4 IU/ml. There were no thromboembolic or neurologic events. We did not retransfuse blood from the extracorporeal circuit or the cardiotomy reservoir after bypass, but because elimination of danaparoid was impaired in this patient and there is no neutraliser available antifactor Xa postoperatively exceeded 0.6 IU/ml for 30 hours. Diffuse bleeding with tamponade resulted. Weaning the patient from the respirator was achieved 12 hours after the last re-exploration. From the 4th postoperative day 750 IU of danaparoid were administered twice daily subcutaneously for thrombosis prevention. On the 6th postoperative day discharge from the ICU was possible. We conclude that the application of danaparoid for cardiopulmonary bypass in patients suffering from acute renal failure may be complicated by hemorrhage.     

Chronic electrical stimulation of the auditory nerve at high stimulus rates: a physiological and histopathological study

The ubiquitous distribution of peroxisomes and the identification of a number of inherited diseases associated with peroxisomal dysfunction indicate that peroxisomes play an essential part in cellular metabolism. Some of the most important metabolic functions of peroxisomes include the synthesis of plasmalogens, bile acids, cholesterol and dolichol, and the oxidation of fatty acids (very long chain fatty acids > C22, branched chain fatty acids (e.g. phytanic acid), dicarboxylic acids, unsaturated fatty acids, prostaglandins, pipecolic acid and glutaric acid). Peroxisomes are also responsible for the metabolism of purines, polyamines, amino acids, glyoxylate and reactive oxygen species (e.g. O-2 and H2O2). Peroxisomal diseases result from the dysfunction of one or more peroxisomal metabolic functions, the majority of which manifest as neurological abnormalities. The quantitation of peroxisomal metabolic functions (e.g. levels of specific metabolites and/or enzyme activity) has become the basis of clinical diagnosis of diseases associated with the organelle. The study of peroxisomal diseases has also contributed towards the further elucidation of a number of metabolic functions of peroxisomes.     

Peripheral nerve stimulation by time-varying magnetic fields

PURPOSE: A study was performed to assess the stimulation threshold for healthy adults using sinusoidally oscillating gradients. METHOD: One hundred thirteen healthy adults were examined in the study. ECG and physiological parameters were measured. All measurements were performed of both the head and the abdomen. The subjects were measured in the supine position with the region of interest positioned in the center of the gradient coils. The measurement was performed for three orthogonal, four oblique, and double oblique orientations. RESULTS: No volunteer reported painful, severe stimulation. The mean thresholds for peripheral stimulation in head and body measurement were similar: 85.5% of stimulation during examination of the head and 87.6% during measurements of the abdomen were reported when the y-gradient was used. CONCLUSION: The greatest frequency of reported stimulations occurs when the y-gradient is used. This was confirmed by the results and supports the hypothesis that orthogonal to the y-axis the body has its largest conductive loop, resulting in the strongest peripheral stimulation.     

Visualisation of nitric oxide released by nerve stimulation

We have visualised nitric oxide (NO) released from the electrically stimulated myenteric plexus and hypogastric nerve. NO was visualised by a reaction with luminol and hydrogen peroxide to generate photons which were counted using a microscope coupled to a photon counting camera. Electrical stimulation of the tissues induced an increase in photon counts which was frequency-dependent and prevented by inhibition of the NO synthase or by tetrodotoxin. The light emitted during nerve stimulation was not only observed at the nerve terminals but also at the axon and soma. Our results indicate that NO released from the whole nerve cell may affect target cells surrounding all parts of the nitrergic neuron. Thus, NO functions as a unique mechanism of synaptic and non-synaptic communication in the nervous system.     

Bradycardia induced by intravascular versus direct stimulation of the vagus nerve

Ricin is a heterodimeric cytotoxin composed of RTB, a galactose binding lectin, and RTA, an enzymatic N-glycosidase. The toxin is endocytosed, and after intracellular routing, RTA is translocated to the cytoplasm where it inactivates ribosomes resulting in a loss of host cell protein synthesis and cell death. We show for the first time that the cytotoxicity against cultured T cells by several RTA mutants is directly proportional to the enzyme activity of RTA, suggesting this is a reliable system to measure translocation effects. Large discrepancies between cytotoxicity and enzyme action for a given pair of toxins are therefore attributable to differences in cell binding, uptake, or membrane translocation. Fluid phase uptake and cytotoxicity of isolated RTA are essentially identical to that of the single chain toxin PAP. This important finding suggests that RTA, and the A chain of class 2 RIPs in general, has not evolved special translocation signals to complement the increased target cell binding facilitated by RTB. Experiments with the lectin RCA and with ebulin suggest those toxins have diminished cytotoxicity probably mediated by comparative deficiencies in B chain binding. Addition of a KDEL sequence to RTA increases fluid phase uptake, consistent with the notion that transport to the ER is important for cytotoxicity. Fusion of MBP or GST to the amino terminus of RTA has little effect on enzyme action or cytotoxicity. This result is not altered by protease inhibitors, suggesting the fusion proteins are probably not cleaved prior to translocation of the toxic A chain and implying that the toxins can carry large passenger proteins into the cytoplasm, an observation with interesting potential for analytical and therapeutic chemistry.     

Assessment of sensory block in epidural anaesthesia by electric stimulation

The onset of sensory block in lumbar epidural anesthesia was investigated in 26 patients, aged 18 to 84 years, employing the loss of discrimination to cold and pinprick, as well as by determining threshold electric stimulation (threshold intensities). A standard dose of 2% mepivacaine with adrenaline, 5 micrograms.ml-1, (0.1 ml per cm body height) was given and the patients' ability to discriminate stimuli within dermatomes T8, T10, T12, L2, L4 and S1 was investigated at five min intervals for 30 min after injection. From the results of the study it is concluded that i) The interval to peak analgesic efficacy of the anaesthetic solution used is < 30 min when assessments are based on the patients' ability to discriminate cold or pinprick but > 30 min when determinations of threshold intensities are employed. ii) Cold discrimination is lost earlier than discrimination to pinprick and at lower threshold intensities. iii) Threshold intensities describe the time course of onset of sensory block more precisely than results of testing by cold or pinprick. iv) The onset of sensory block was found to be positively correlated to the age of patients in the following respects: a) Threshold intensities during early onset in all investigated dermatomes except L2. b) Intensity of block in T8, T10, and S1 at the end of the study period. c) Time to loss of discrimination to cold and pinprick in T12, L2 and S1, and d) Threshold intensities at loss of discrimination to cold and pinprick. We propose that determinations of threshold intensities offer distinct advantages over conventional testing by cold and pinprick discrimination, especially when detailed analyses of the sensory blocking effects of local anaesthetic drugs are being investigated.     

Reductions in self-injury produced by transcutaneous electrical nerve stimulation

Transcutaneous electrical nerve stimulation is used to reduce pain but also may be useful for self-injurious behavior (SIB). In the current investigation, a microcurrent electromedical device, classified as a transcutaneous electrical nerve stimulator (TENS), was applied with a man with Down syndrome who displayed SIB that persisted in the absence of social contingencies. Although clinically significant results were not maintained, a clear difference in the rates of SIB during active and inactive TENS was observed.     

Directional masking of phase locking in the amphibian auditory nerve

Directional masking in the amphibian auditory periphery was investigated by presenting frogs with a continuous tone from above and a continuous broadband noise from four different horizontal directions. This paradigm mimics the natural situation in which frogs are located in three-dimensional space and interference can and does arise from any direction. Intracellular recordings were made from single auditory-nerve fibers of the anesthetized adult leopard frogs using a dorsal approach. Vector strength (VS) and the mean preferred firing phase (MP) were measured for 94 low-frequency fibers. Thirty-six percent of the fibers demonstrated direction sensitivity of noise masking of VS. Most fibers exhibited a maximum decrease in VS at 90 degrees or 270 degrees noise incident angle and a minimum decrease in VS at 0 degrees or 180 degrees noise incident angle, suggesting higher noise susceptibility to the lateral fields than to the anterior or posterior field. Forty-nine percent of the fibers demonstrated direction sensitivity of noise masking of MP. Maximum shift in MP occurred most often at 90 degrees or 180 degrees noise incident angle, whereas minimum shift in MP occurred most frequently at 0 degrees or 270 degrees noise incident angle, suggesting higher noise susceptibility to the ipsilateral or posterior field than to the contralateral or anterior field. The difference in the directionality patterns of VS and MP suggests different mechanisms underlying noise masking of these two measures of phase locking in the amphibian auditory nerve.     

Peculiarity of soleus motor potentials evoked by transcranial magnetic stimulation and electrical stimulation of tibial nerve

Fas (Apo-1/CD95) ligand (FasL) is a cytotoxic molecule used by T lymphocytes and natural killer cells for target-cell killing and by nonmalignant and malignant cells in the suppression of immune responses. In this study, FasL expression in B- and T-cell non-Hodgkin's lymphomas was investigated by paraffin immunohistochemical analysis. FasL expression was found to be weak in nonaggressive lymphomas (chronic lymphocytic leukemia/small lymphocytic lymphoma, lymphoplasmacytoid lymphoma, Grade 1 follicular center cell lymphoma) and mantle cell lymphoma but strong in aggressive B-cell lymphomas (diffuse large B-cell lymphoma, Burkitt's-lymphoma). Precursor B-lymphoblastic lymphomas were more heterogeneous, with expression varying from weak to strong. In T-cell lymphomas (anaplastic large-cell lymphoma; peripheral T-cell lymphoma, unspecified), strong FasL expression was observed. Apparently, FasL expression is not limited to neoplasms derived from T cells or natural killer cells, and it might play a supporting role in the progression of non-Hodgkin's lymphomas.