NMR spectroscopy and brain diseases. Clinical applications

We studied the relationship between auditory activity in the midbrain and selective phonotaxis in females of the treefrog, Pseudacris crucifer. Gravid females were tested in two-stimulus playback tests using synthetic advertisement calls of different frequencies (2600 versus 2875 Hz; 2800 versus 3500 Hz; 2600 versus 3500 Hz). Tests were conducted with and without a background of synthesized noise, which was filtered to resemble the spectrum of a chorus of spring peepers. There were no significant preferences for calls of any frequency in the absence of background noise. With background noise, females preferred calls of 3500 Hz to those of 2600 Hz. Multi-unit recordings of neural responses to synthetic sounds were made from the torus semicircularis of the same females following the tests of phonotaxis. We measured auditory threshold at 25 frequencies (1800-4200 Hz) as well as the magnitude of the neural response when stimulus amplitude was held constant and frequency was varied. This procedure yielded isointensity response contours, which we obtained at six amplitudes in the absence of noise and at the stimulus amplitude used during the phonotaxis tests with background noise. Individual differences in audiograms and isointensity responses were poorly correlated with behavioural data except for the test of 2600 Hz versus 3500 Hz calls in noise. The shape of the neural response contours changed with stimulus amplitude and in the presence of the simulated frog chorus. At 85 dB sound pressure level (SPL), the level at which females were tested, the contours of females were quite flat. The contours were more peaked at lower SPLs as well as during the broadcast of chorus noise and white noise at an equivalent spectrum level (45-46 dB/Hz). Peaks in the isointensity response plots of most females occurred at stimulus frequencies ranging from 3200 to 3400 Hz, frequencies close to the median best excitatory frequency (BEF) of 3357 Hz but higher than the mean of the mid-frequency of the male advertisement call (3011 Hz). Addition of background noise may cause a shift in the neural response-intensity level functions. Our results highlight the well-known nonlinearity of the auditory system and the danger inherent in focusing solely on threshold measures of auditory sensitivity when studying the proximate basis of female choice. The results also show an unexpected effect of the natural and noisy acoustic environment on behaviour and responses of the auditory system. Copyright 1998 The Association for the Study of Animal Behaviour.     

Low-frequency suppression of auditory nerve responses to characteristic frequency tones

The effects of low-frequency (50, 100, 200 and 400 Hz) 'suppressor' tones on responses to moderate-level characteristic frequency (CF) tones were measured in chinchilla auditory nerve fibers. Two-tone interactions were evident at suppressor intensities of 70-100 dB SPL. In this range, the average response rate decreased as a function of increasing suppressor level and the instantaneous response rate was modulated periodically. At suppression threshold, the phase of suppression typically coincided with basilar membrane displacement toward scala tympani, regardless of CF. At higher suppressor levels, two suppression maxima coexisted, synchronous with peak basilar membrane displacement toward scala tympani and scala vestibuli. Modulation and rate-suppression thresholds did not vary as a function of spontaneous activity and were only minimally correlated with fiber sensitivity. Except for fibers with CF < 1 kHz, modulation and rate-suppression thresholds were lower than rate and phase-locking thresholds for the suppressor tones presented alone. In the case of high-CF fibers with low spontaneous activity, excitation thresholds could exceed suppression thresholds by more than 30 dB. The strength of modulation decreased systematically with increasing suppressor frequency. For a given suppressor frequency, modulation was strongest in high-CF fibers and weakest in low-CF fibers. The present findings strongly support the notion that low-frequency suppression in auditory nerve fibers largely reflects an underlying basilar membrane phenomenon closely related to compressive non-linearity.     

Representation of acoustic signals in the eighth nerve of the Tokay gecko. II. Masking of pure tones with noise

Acoustic signals are generally encoded in the peripheral auditory system of vertebrates by a duality scheme. For frequency components that fall within the excitatory tuning curve, individual eighth nerve fibers can encode the effective spectral energy by a spike-rate code, while simultaneously preserving the signal waveform periodicity of lower frequency components by phase-locked spike-train discharges. To explore how robust this duality of representation may be in the presence of noise, we recorded the responses of auditory fibers in the eighth nerve of the Tokay gecko to tonal stimuli when masking noise was added simultaneously. We found that their spike-rate functions reached plateau levels fairly rapidly in the presence of noise, so the ability to signal the presence of a tone by a concomitant change in firing rate was quickly lost. On the other hand, their synchronization functions maintained a high degree of phase-locked firings to the tone even in the presence of high-intensity masking noise, thus enabling a robust detection of the tonal signal. Critical ratios (CR) and critical bandwidths showed that in the frequency range where units are able to phaselock to the tonal periodicity, the CR bands were relatively narrow and the bandwidths were independent of noise level. However, to higher frequency tones where phaselocking fails and only spike-rate codes apply, the CR bands were much wider and depended upon noise level, so that their ability to filter tones out of a noisy background degraded with increasing noise levels. The greater robustness of phase-locked temporal encoding contrasted with spike-rate coding verifies a important advantage in using lower frequency signals for communication in noisy environments.     

Sensitivity analysis of kernel estimates: implications in nonlinear physiological system identification

Many techniques have been developed for the estimation of the Volterra/Wiener kernels of nonlinear systems, and have found extensive application in the study of various physiological systems. To date, however, we are not aware of methods for estimating the reliability of these kernels from single data records. In this study, we develop a formal analysis of variance for least-squares based nonlinear system identification algorithms. Expressions are developed for the variance of the estimated kernel coefficients and are used to place confidence bounds around both kernel estimates and output predictions. Specific bounds are developed for two such identification algorithms: Korenberg's fast orthogonal algorithm and the Laguerre expansion technique. Simulations, employing a model representative of the peripheral auditory system, are used to validate the theoretical derivations, and to explore their sensitivity to assumptions regarding the system and data. The simulations show excellent agreement between the variances of kernel coefficients and output predictions as estimated from the results of a single trial compared to the same quantities computed from an ensemble of 1000 Monte Carlo runs. These techniques were validated with white and nonwhite Gaussian inputs and with white Gaussian and nonwhite non-Gaussian measurement noise on the output, provided that the output noise source was independent of the test input.     

Auditory filter shapes of normal-hearing and hearing-impaired listeners in continuous broadband noise

Listeners with sensorineural hearing impairment typically exhibit auditory processing deficits such as reduced frequency and/or temporal resolution. Such deficits may represent separate sequela of auditory pathology or may result directly from the sensitivity loss and the requirement to listen at high levels. To assess the impact of increased thresholds on frequency resolution, auditory filter characteristics were determined for hearing-impaired and normal-hearing listeners at 500 and 2000 Hz in the presence of continuous broadband noise meant as a rough simulation of hearing loss. In the fitting procedure, the low-frequency skirt of the derived auditory filter was allowed to vary as a function of signal level, permitting different filter shapes to be estimated at high versus low signal levels. Listeners with moderate hearing losses at 2000 Hz demonstrated near-normal auditory filter shapes for lower signal levels, but increasingly broad and asymmetric filters as signal level was raised. At 500 Hz, where hearing losses were mild, filter bandwidths increased little at the higher signal levels. The presence of broadband noise had essentially no effect on filter shapes of either listener group. The filter shape abnormalities demonstrated by listeners with moderate hearing loss, which were not observed in normal-hearing listeners at the same signal levels, indicate that poor frequency resolution in these patients for high-intensity stimuli does not follow directly from decreased sensitivity, but instead reflects an independent pathology.     

A model for the responses of low-frequency auditory-nerve fibers in cat

A computational model was developed for the responses of low-frequency auditory-nerve (AN) fibers in cat. The goal was to produce realistic temporal response properties and average discharge rates in response to simple and complex stimuli. Temporal and average-rate properties of AN responses change as a function of sound-pressure level due to nonlinearities in the auditory periphery. The input stage of the AN model is a narrow-band filter that simulates the mechanical tuning of the basilar membrane. The parameters of this filter vary continuously as a function of stimulus level via a feedback mechanism, simulating the compressive nonlinearity associated with the mechanics of the basilar membrane. A memoryless, saturating nonlinearity and two low-pass filters simulate transduction and membrane properties of the inner hair cell (IHC). A diffusion model for the IHC-AN synapse introduces adaptation. Finally, a nonhomogeneous Poisson process, modified by absolute and relative refractoriness, provides the output discharge times. Responses to several different stimuli are presented. These responses illustrate nonlinear temporal response properties that cannot be achieved with linear models for AN fibers.     

Spike train encoding by regular-spiking cells of the visual cortex

1. To study the encoding of input currents into output spike trains by regular-spiking cells, we recorded intracellularly from slices of the guinea pig visual cortex while injecting step, sinusoidal, and broadband noise currents. 2. When measured with sinusoidal currents, the frequency tuning of the spike responses was markedly band-pass. The preferred frequency was between 8 and 30 Hz, and grew with stimulus amplitude and mean intensity. 3. Stimulation with broadband noise currents dramatically enhanced the gain of the spike responses at low and high frequencies, yielding an essentially flat frequency tuning between 0.1 and 130 Hz. 4. The averaged spike responses to sinusoidal currents exhibited two nonlinearities: rectification and spike synchronization. By contrast, no nonlinearity was evident in the averaged responses to broadband noise stimuli. 5. These properties of the spike responses were not present in the membrane potential responses. The latter were roughly linear, and their frequency tuning was low-pass and well fit by a single-compartment passive model of the cell membrane composed of a resistance and a capacitance in parallel (RC circuit). 6. To account for the spike responses, we used a "sandwich model" consisting of a low-pass linear filter (the RC circuit), a rectification nonlinearity, and a high-pass linear filter. The model is described by six parameters and predicts analog firing rates rather than discrete spikes. It provided satisfactory fits to the firing rate responses to steps, sinusoids, and broadband noise currents. 7. The properties of spike encoding are consistent with temporal nonlinearities of the visual responses in V1, such as the dependence of response frequency tuning and latency on stimulus contrast and bandwidth. We speculate that one of the roles of the high-frequency membrane potential fluctuations observed in vivo could be to amplify and linearize the responses to lower, stimulus-related frequencies.     

Frequency tuning and spontaneous activity in the auditory nerve and cochlear nucleus magnocellularis of the barn owl Tyto alba

Single-unit recordings were obtained from the brain stem of the barn owl at the level of entrance of the auditory nerve. Auditory nerve and nucleus magnocellularis units were distinguished by physiological criteria, with the use of the response latency to clicks, the spontaneous discharge rate, and the pattern of characteristic frequencies encountered along an electrode track. The response latency to click stimulation decreased in a logarithmic fashion with increasing characteristic frequency for both auditory nerve and nucleus magnocellularis units. The average difference between these populations was 0.4-0.55 ms. The average most sensitive thresholds were approximately 0 dB SPL and varied little between 0.5 and 9 kHz. Frequency-threshold curves showed the simple V shape that is typical for birds, with no indication of a low-frequency tail. Frequency selectivity increased in a gradual, power-law fashion with increasing characteristic frequency. There was no reflection of the unusual and greatly expanded mapping of higher frequencies on the basilar papilla of the owl. This observation is contrary to the equal-distance hypothesis that relates frequency selectivity to the spatial representation in the cochlea. On the basis of spontaneous rates and/or sensitivity there was no evidence for distinct subpopulations of auditory nerve fibers, such as the well-known type I afferent response classes in mammals. On the whole, barn owl auditory nerve physiology conformed entirely to the typical patterns seen in other bird species. The only exception was a remarkably small spread of thresholds at any one frequency, this being only 10-15 dB in individual owls. Average spontaneous rate was 72.2 spikes/s in the auditory nerve and 219.4 spikes/s for nucleus magnocellularis. This large difference, together with the known properties of endbulb-of-Held synapses, suggests a convergence of approximately 2-4 auditory nerve fibers onto one nucleus magnocellularis neuron. Some auditory nerve fibers as well as nucleus magnocellularis units showed a quasiperiodic spontaneous discharge with preferred intervals in the time-interval histogram. This phenomenon was observed at frequencies as high as 4.7 kHz.     

Continuous intense noise masks auditory feedback and inner speech.

During World War II, the late S. S. Stevens (1972) concluded that continuous intense noise does not degrade human performance, except by masking auditory cues. In the 1950s (1953, 1954, 1955, 1957, 1958), D. E. Broadbent claimed that continuous intense noise does affect people directly, by a mechanism other than masking. But recent experimental checks indicate that masking of the auditory feedback cues occurred in Broadbent's early experiments and in experiments reported subsequently by others. The auditory feedback tells the man that his response has been recorded. This is a help when there is a confusing directional relationship between control and display, when the control buttons are difficult to locate, and when considerable control pressure is required. Sometimes the auditory feedback helps to augment inadequate visual feedback. The remaining experiments in which continuous intense noise reliably degrades performance involve verbal working memory. Here, the noise can be said to interfere with or mask inner speech. Yet current explanations of the detrimental effects of continuous intense noise usually follow Broadbent and ignore masking in favor of nonspecific concepts like distraction, the funneling of attention, or overarousal. (70 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Temporal frequency modulates reaction time responses to first-order and second-order motion.

This study investigated the effect of temporal frequency and modulation depth on reaction times for discriminating the direction of first-order (luminance-defined) and second-order (contrast-defined) motion, equated for visibility using equal multiples of direction-discrimination threshold. Results showed that reaction times were heavily influenced by temporal frequency, especially in the case of second-order motion. At 1 Hz, reaction times were faster for first-order compared with second-order motion. As temporal frequency increased, reaction times for first-order motion decreased slightly, but those for second-order motion decreased more rapidly. At 8 Hz, reaction times for second-order motion were, in many cases, faster than those for first-order motion. Reaction times decreased as stimulus modulation depth increased at approximately the same rate for both motion types. The findings demonstrate that behavioral response latencies to first-order and second-order motion are dependent on specific stimulus parameters and may, in some cases, be shorter in response to second-order compared with first-order motion. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Normal median near nerve potential

In routine studies of sensory nerve conduction, only fibers > or = 7 microns in diameter are analyzed. The late components which originate from thinner fibers are not detected. This explains why a normal sensory action potential (SAP) may be recorded in patients with peripheral neuropathies and sensory loss. In the present study we investigated the late component of the median SAP with a near nerve needle electrode technique in 14 normal volunteers (7 men and 7 women), aged 34.5 +/- 14.8 years. The stimulus consisted of rectangular pulses of 0.2-ms duration at a frequency of 1 Hz with an intensity at least 6 times greater than the threshold value for the main component. Five hundred to 2000 sweep averagings were performed. The duration of analysis was 40 or 50 ms and the wave analysis frequency was 200 (-6 dB/oct) to 3000 Hz (-12 dB/oct). We used an apparatus with a two-channel amplifier system, 200 M omega or more of entry impedance and a noise level of 0.7 microVrms or less. The main component mean amplitude, conduction velocity and latency and the late component mean amplitude, conduction velocity and latency were respectively (mean +/- SD): 26.5 +/- 5.42 microV, 56.8 +/- 5.42 m/s, 3.01 +/- 0.31 ms, 0.12 +/- 0.04 microV, 16.4 +/- 2.95 m/s and 10.6 +/- 2.48 ms. More sophisticated equipment has an internal noise of 0.6 microVrms. These data demonstrate that the technique can now be employed to study thin fiber neuropathies, like in leprosy, using commercial electromyographs, even in non-academic practices.     

Nonlinear analysis of visual evoked potentials elicited by color stimulation

The relationship between chromatically modulated stimuli and visual evoked potentials (VEPs) was considered. VEPs of normal subjects elicited by chromatically modulated stimuli were measured under several color adaptations, and their binary kernels were estimated. Up to the second-order, binary kernels obtained from VEPs were so characteristic that the VEP-chromatic modulation system showed second-order nonlinearity. First-order binary kernels depended on the color of the stimulus and adaptation, whereas second-order kernels showed almost no difference. This result indicates that the waveforms of first-order binary kernels reflect perceived color (hue). This supports the suggestion that kernels of VEPs include color responses, and could be used as a probe with which to examine the color visual system.     

Effect of sodium benzoate on cerebral and hepatic energy metabolites in spf mice with congenital hyperammonemia

The outer hair cell (OHC) is known to have the ability to change its length in response to voltage changes across its membrane. The apparent function of this OHC motility is to enhance the tuning of the basilar membrane. The model presented in this paper represents the displacement-to-voltage and voltage-to-displacement transducers of the OHC explicitly, each as low-pass filter functions. The model results show that this OHC representation is sufficient to provide a model of cochlear mechanics with mechanical tuning at the inner hair cell which is comparable to the threshold tuning curves observed in single auditory nerve fibers. The enhancement of tuning provided by OHC motility can be interpreted as the combined action of a cochlear amplifier and a second filter. This model demonstrates that realistic cochlear tuning does not require intrinsic resonance in any cochlear structure other than the basilar membrane.     

Modeling inhibition of type II units in the dorsal cochlear nucleus

Type II units in the dorsal cochlear nucleus (DCN) are characterized by vigorous but nonmonotonic responses to best frequency tones as a function of sound pressure level, and relatively weak responses to noise. A model of DCN neural circuitry was used to explore two hypothetical mechanisms by which neurons may be endowed with type II unit response properties. Both mechanisms assume that type II units receive excitatory input from auditory nerve (AN) fibers and inhibitory input from an unspecified class of cochlear nucleus interneurons that also receive excitatory AN input. The first mechanism, a lateral inhibition (LI) model, supposes that type II units receive inhibitory input from a number of narrowly tuned interneurons whose best frequencies (BFs) flank the BF of the type II unit. Tonal stimuli near BF result in only weak inhibitory input, but broadband stimuli recruit enough lateral inhibitors to greatly weaken the type II unit response. The second mechanism, a wideband inhibition (WBI) model, supposes that type II units receive inhibitory input from interneurons that are broadly tuned so that they respond more vigorously to broadband stimuli than to tones. Physiological and anatomical evidence points to the possible existence of such a class of neurons in the cochlear nucleus. The model extends an earlier computer model of an iso-frequency DCN patch to multiple frequency slices and adds a population of interneurons to provide the inhibition to model type II units (called 12-cells). The results show that both mechanisms accurately simulate responses of type II units to tones and noise. An experimental paradigm for distinguishing the two mechanisms is proposed.     

Differential susceptibility of diaphragm muscle fibers to neuromuscular transmission failure

The pattern of glycogen utilization was used to determine whether various muscle fiber types in the rat diaphragm are differentially susceptible to neuromuscular transmission failure. Muscle segments from the midcostal region were repetitively stimulated directly or via the phrenic nerve at 10 or 75 Hz. Muscle fiber types were classified histochemically as type I, IIa, or IIb. The amount of muscle fiber glycogen depletion with direct stimulation depended on stimulation rate (75 Hz > 10 Hz) and fiber type (IIb > IIa > I). However, with nerve stimulation, muscle fiber glycogen depletion did not display the same dependency on stimulation rate (10 Hz > 75 Hz), although with stimulation at 10 Hz, the same rank order of fiber depletion was observed (IIb > IIa > I). This rank order of depletion was reversed (I > IIa > IIb) during repetitive stimulation of the nerve at 75 Hz. By intermittently stimulating the muscle directly during continuous nerve stimulation, we determined that neuromuscular transmission failure contributed significantly to the force decline after 2 min of stimulation at 75 Hz but relatively little to the force decline after 2 min of stimulation at 10 Hz. A significantly greater fraction of the force decline could be attributed to neuromuscular transmission failure with repetitive bouts of stimulation at 10 Hz. We conclude that neuromuscular transmission failure causes a significant portion of the force decline after 8 min of stimulation at 10 and 75 Hz, that all diaphragm fiber types are susceptible to neuromuscular transmission failure, but that type IIb fibers are particularly susceptible at higher frequencies of stimulation.     

Single olivocochlear neurons in the guinea pig. I. Binaural facilitation of responses to high-level noise

Single medial olivocochlear (MOC) neurons were recorded from the cochlea of the anesthetized guinea pig. We used tones and noise presented monaurally and binaurally and measured responses for sounds up to 105 dB sound pressure level (SPL). For monaural sound, MOC neuron firing rates were usually higher for noise bursts than tone bursts, a situation not observed for afferent fibers of the auditory nerve that were sampled in the same preparations. MOC neurons also differed from afferent fibers in having less saturation of response. Some MOC neurons had responses that continued to increase even at high sound levels. Differences between MOC and afferent responses suggest that there is convergence in the pathway to olivocochlear neurons, possibly a combination of inputs that are at the characteristic frequency (CF) with others that are off the CF. Opposite-ear noise almost always facilitated the responses of MOC neurons to sounds in the main ear, the ear that best drives the unit. This binaural facilitation depends on several characteristics that pertain to the main ear: it is higher in neurons having a contralateral main ear (contra units), it is higher at main-ear sound levels that are moderate (approximately 65 dB SPL), and it is higher in neurons with low discharge rates to main-ear stimuli. Facilitation also depends on parameters of the opposite-ear sound: facilitation increases with noise level in the opposite ear until saturating, is greater for continuous noise than noise bursts, and is usually greater for noise than for tones. Using optimal opposite-ear facilitators and high-level stimuli, the firing rates of olivocochlear neurons range up to 140 spikes/s, whereas for moderate-level monaural stimuli the rates are <80 spikes/s. At high sound levels, firing rates of olivocochlear neurons increase with CF, an increase that may compensate for the known lower effectiveness of olivocochlear synapses on outer hair cells responding to high frequencies. Overall, our results demonstrate a high MOC response for binaural noise and suggest a prominent role for the MOC system in environments containing binaural noise of high level.     

Frequency tuning of basilar membrane and auditory nerve fibers in the same cochleae

Responses to tones of a basilar membrane site and of auditory nerve fibers innervating neighboring inner hair cells were recorded in the same cochleae in chinchillas. At near-threshold stimulus levels, the frequency tuning of auditory nerve fibers closely paralleled that of basilar membrane displacement modified by high-pass filtering, indicating that only relatively minor signal transformations intervene between mechanical vibration and auditory nerve excitation. This finding establishes that cochlear frequency selectivity in chinchillas (and probably in mammals in general) is fully expressed in the vibrations of the basilar membrane and renders unnecessary additional ("second") filters, such as those present in the hair cells of the cochleae of reptiles.     

Guanylate cyclase activity in the inner ear and auditory nerve of the rat

Novel molecular mediation in the sound transductional process is implicitly suggested. We investigated the presence of the cGMP-synthesis enzyme, guanylate cyclase, in Corti's organ and auditory nerve of the rat. The soluble guanylate cyclase activity found was sensitive to changes of sound intensity in the different acoustic media used, suggesting a potential role for the system that involves this enzyme. The guanylate cyclase activity appeared to be inversely related (in the inner ear) with the sound intensity to which the animals were exposed; different behavior was observed for the auditory nerve. The enzymatic activity found in Corti's organ, a direct bio-receptor of sound, represents the first reported enzymatic activity of this type in this tissue, which apparently could be influenced by the intensity of a physical stimulus such as sound. Finally, an adequate ionic environment appears to play a potential role in the expression of the changes observed, indicating that it may function according to the requirements of the biological sensor.