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Subunit contributions to phosphorylation-dependent modulation of bovine rod cyclic nucleotide-gated channels.

Cyclic nucleotide-gated (CNG) channels in rod photoreceptors transduce a decrease in cGMP into hyperpolarization during the light response. Insulin-like growth factor-1 (IGF-1) increases light responses by increasing the cGMP sensitivity of CNG channels, an event mediated by a protein tyrosine phosphatase. Native rod CNG channels are heteromultimers, composed of three CNGA1 subunits and one CNGB1 subunit. Previous studies on heterologously expressed rod CNG channels show that a specific tyrosine in the CNGA1 subunit (Y498) is required for modulation by protein tyrosine phosphatases, protein tyrosine kinases and IGF-1. Here we show that the CNGB1 subunit contains a specific tyrosine (Y1097) that is important for modulation of heteromeric channels by tyrosine phosphorylation. Direct biochemical measurements demonstrate 32P-labelling of CNGA1Y498 and CNGB1Y1097. Replacement of either Y498 of CNGA1 or Y1097 of CNGB1 with phenylalanine reduces modulation, and removal of both tyrosines eliminates modulation. Unlike CNGA1, CNGB1 does not exhibit activity dependence of modulation by tyrosine phosphorylation. Hence both CNGA1 and CNGB1 subunits contribute to phosphorylation-dependent modulation of rod CNG channels, but the phosphorylation states of the two subunits are regulated in different ways.

Animals↗

Mechanisms of H+ modulation of glycinergic response in rat sacral dorsal commissural neurons.

Many ionotropic receptors are modulated by extracellular H+. So far, few studies have directly addressed the role of such modulation at synapses. In the present study, we investigated the effects of changes in extracellular pH on glycinergic miniature inhibitory postsynaptic currents (mIPSCs) as well as glycine-evoked currents (IGly) in mechanically dissociated spinal neurons with native synaptic boutons preserved. H+ modulated both the mIPSCs and IGly biphasically, although it activated an amiloride-sensitive inward current by itself. Decreasing extracellular pH reversibly inhibited the amplitude of the mIPSCs and IGly, while increasing external pH reversibly potentiated these parameters. Blockade of acid-sensing ion channels (ASICs) with amiloride, the selective antagonist of ASICs, or decreasing intracellular pH did not alter the modulatory effect of H+ on either mIPSCs or IGly. H+ shifted the EC50 of the glycine concentration-response curve from 49.3 +/- 5.7 microM at external pH 7.4 to 131.5 +/- 8.1 microM at pH 5.5, without altering the Cl- selectivity of the glycine receptor (GlyR), the Hill coefficient and the maximal IGly, suggesting a competitive inhibition of IGly by H+. Both Zn2+ and H+ inhibited IGly. However, H+ induced no further inhibition of IGly in the presence of a saturating concentration of Zn2+. In addition, H+ significantly affected the kinetics of glycinergic mIPSCs and IGly. It is proposed that H+ and/or Zn2+ compete with glycine binding and inhibit the amplitude of glycinergic mIPSCs and IGly. Moreover, binding of H+ induces a global conformational change in GlyR, which closes the GlyR Cl- channel and results in the acceleration of the seeming desensitization of IGly as well as speeding up the decay time constant of glycinergic mIPSCs. However, the deprotonation rate is faster than the unbinding rate of glycine from the GlyR, leading to reactivation of the undesensitized GlyR after washout of agonist and the appearance of a rebound IGly. H+ also modulated the glycine cotransmitter, GABA-activated current (IGABA). Taken together, the results support a "conformational coupling" model for H+ modulation of the GlyR and suggest that H+ may act as a novel modulator for inhibitory neurotransmission in the mammalian spinal cord.

2-Amino-5-phosphonovalerate↗

Phase-dependent and task-dependent modulation of stretch reflexes during rhythmical hand tasks in humans.

Phase-dependent and task-dependent modulation of reflexes has been extensively demonstrated in leg muscles during locomotory activity. In contrast, the modulation of reflex responses of hand muscles during rhythmic movement is poorly documented. The objective of this study was to determine whether comparable reflex modulation occurs in muscles controlling finger motions during rhythmic, fine-motor tasks akin to handwriting. Twelve healthy subjects performed two rhythmic tasks while reflexes were evoked by mechanical perturbations applied at various phases of each task. Electromyograms (EMGs) were recorded from four hand muscles, and reflexes were averaged during each task relative to the movement phase. Stretch reflexes in all four muscles were found to be modulated in amplitude with respect to the phase of the rhythmic tasks, and also to vary distinctly with the tasks being conducted. The extent and pattern of reflex modulation differed between muscles in the same task, and between tasks for the same muscle. Muscles with a primary role in each task showed a higher correlation between reflex response and background EMG than other muscles. The results suggest that the modulation patterns observed may reflect optimal strategies of central-peripheral interactions in controlling the performance of fine-motor tasks. As with comparable studies on locomotion, the phase-dependency of the stretch reflexes implies a dynamically fluctuating role of proprioceptive feedback in the control of the hand muscles. The clear task-dependency is also consistent with a dynamic interaction of sensory feedback and central programming, presumably adapted to facilitate the successful performance of the different fine-motor tasks.

Adult↗

Rate dependency of beta-adrenergic modulation of repolarizing currents in the guinea-pig ventricle.

Beta-adrenergic stimulation modulates ventricular currents and sinus cycle length (CL). We investigated how changes in CL affect the current induced by isoprenaline (Iso) during the action potential (AP) of guinea-pig ventricular myocytes. Action-potential clamp was applied at CLs of 250 and 1000 ms to measure: (1) the net current induced by 0.1 microm Iso (I(Iso)); (2) the L-type Ca2+ current I(CaL) and slow delayed rectifier current I(Ks) components of I(Iso) (I(IsoCa) and I(IsoK)), identified as the Iso-induced current sensitive to nifedipine and HMR1556, respectively; and (3) I(Iso) persisting after inhibition of both I(Ca) and I(Ks) (I(isoR)). The pause dependency of I(Ks) and its modulation were evaluated in voltage-clamp experiments. The rate dependency of the duration of the action potential at 90% repolarization (APD90) and its modulation by isoprenaline were tested in current-clamp experiments. At a CL of 250 ms I(Iso) was inward during initial repolarization and reversed at 59% of APD90. At a CL of 1000 ms I(Iso) became mostly inward in all cells. Switching to shorter CL did not change I(IsoCa) and I(IsoK) amplitudes, but moved their peak amplitudes to earlier repolarization; I(IsoR) was independent of CL. Acceleration of I(IsoK) at shorter CL was based on faster pause dependency of I(Ks) activation rate. The 'restitution' of activation rates was modulated by isoprenaline. The APD90-CL relation was rotated anticlockwise by isoprenaline and crossed the control curve at a CL of 150 ms (400 beats min(-1)). We conclude that: (1) isoprenaline induced markedly different current profiles according to pacing rate, involving CL-dependent I(Ca) and I(Ks) modulation; (2) the effect of isoprenaline on APD90 was CL dependent, and negligible during tachycardia; and (3) during sympathetic activation, repolarization stability may involve matched modulation of sinus rate and repolarizing currents.

Action Potentials↗

Neurosteroid modulation of respiratory rhythm in rats during the perinatal period.

Neurosteroids regulate neuronal excitability and are expressed at particularly high levels in the CNS during the perinatal period. Further, neurosteroid levels are increased by a variety of stressors including hypoxia, asphyxia, parturition, ethanol exposure and infection. One mechanism by which neurosteroids regulate neuronal activity is by negative or positive modulation of GABA(A) receptor function. Perinatal respiration is strongly modulated by GABAergic synaptic drive, and GABA release is increased during hypoxia to contribute to hypoxia-induced depression of neonatal ventilation. Here, we use in vitro and in vivo rat models to test the hypothesis that GABA(A) receptor-mediated modulation of perinatal respiration is markedly influenced by the presence of neurosteroids. The principal finding of this study was that the efficacy of GABA(A) receptor-mediated modulation of respiratory membrane potential and rhythmogenesis is markedly enhanced by allopregnanolone and depressed by dehydroepiandrosterone sulphate. These data demonstrate that the modulation of breathing via GABA(A) receptor activation will be determined by the overall balance of negative and positive neurosteroid modulators within respiratory nuclei. This adds a level of complexity that must be considered when examining the depression of breathing in mammals associated with various behavioural states and pathogenic conditions such as apnoea and sudden death suspected to be associated with central respiratory dysfunction.

Action Potentials↗

Simulation of progressive deformities in adolescent idiopathic scoliosis using a biomechanical model integrating vertebral growth modulation.

While the etiology and pathogenesis of adolescent idiopathic scoliosis are still not well understood, it is generally recognized that it progresses within a biomechanical process involving asymmetrical loading of the spine and vertebral growth modulation. This study intends to develop a finite element model incorporating vertebral growth and growth modulation in order to represent the progression of scoliotic deformities. The biomechanical model was based on experimental and clinical observations, and was formulated with variables integrating a biomechanical stimulus of growth modulation along directions perpendicular (x) and parallel (y, z) to the growth plates, a sensitivity factor beta to that stimulus and time. It was integrated into a finite element model of the thoracic and lumbar spine, which was personalized to the geometry of a female subject without spinal deformity. An imbalance of 2 mm in the right direction at the 8th thoracic vertebra was imposed and two simulations were performed: one with only growth modulation perpendicular to growth plates (Sim1), and the other one with additional components in the transverse plane (Sim2). Semi-quantitative characterization of the scoliotic deformities at each growth cycle was made using regional scoliotic descriptors (thoracic Cobb angle and kyphosis) and local scoliotic descriptors (wedging angle and axial rotation of the thoracic apical vertebra). In all simulations, spinal profiles corresponded to clinically observable configurations. The Cobb angle increased non-linearly from 0.3 degree to 34 degrees (Sim1) and 20 degrees (Sim2) from the first to last growth cycle, adequately reproducing the amplifying thoracic scoliotic curve. The sagittal thoracic profile (kyphosis) remained quite constant. Similarly to clinical and experimental observations, vertebral wedging angle of the thoracic apex progressed from 2.6 degrees to 10.7 degrees (Sim1) and 7.8 degrees (Sim2) with curve progression. Concomitantly, vertebral rotation of the thoracic apex increased of 10 degrees (Sim1) and 6 degrees (Sim2) clockwise, adequately reproducing the evolution of axial rotation reported in several studies. Similar trends but of lesser magnitude (Sim2) suggests that growth modulation parallel to growth plates tend to counteract the growth modulation effects in longitudinal direction. Overall, the developed model adequately represents the self-sustaining progression of vertebral and spinal scoliotic deformities. This study demonstrates the feasibility of the modeling approach, and compared to other biomechanical studies of scoliosis it achieves a more complete representation of the scoliotic spine.

Adolescent↗

Sensitivity of helium beam-modulator design to uncertainties in biological data.

The goal in designing beam-modulating devices for heavy charged-particle therapy is to achieve uniform biological effects across the spread-peak region of the beam. To accomplish this, the linear-quadratic model for cell survival has been used to describe the biological response of the target cells to charged-particle radiation. In this paper, the sensitivity of the beam-modulator design in the high-dose region to the values of the linear-quadratic variables alpha and beta has been investigated for a 215-MeV/u helium beam, and implications for higher LET beams are discussed. The major conclusions of this work are that, for helium over the LET range of 2 to 16 keV/mu, uncertainties in measuring alpha and beta for a given cell type which are of the order of 20% or less have a negligible effect on the beam-modulator design (i.e., on the slope of the spread Bragg peak); uncertainties less than or equal to 10% in the dose-averaged LET at each depth are unimportant; and, if the linear-quadratic variables for the tumor differ from those used in the beam-modulator design by a constant factor between about 0.5 and 3, then the resultant nonuniformity in the photon-equivalent dose delivered to the tumor is within +/- 25%. It is also shown that for any ion, if the nominal values of alpha or beta used by the beam-modulator design program differ from their actual values by a constant factor, then the maximum errors possible in the beam-modulator design may be characterized by two limiting depth-dose curves such that the ratio of the dose at the proximal end of the spread Bragg curve to the dose at the distal end of the spread peak is given by alpha distal/alpha prox for the steepest curve, and square root of beta distal/beta prox for the flattest curve.

Cell Survival↗

The influence of angular misalignment on fixed-portal intensity modulated radiation therapy.

A method has been developed to estimate potential dose errors due to linear accelerator angular setting misalignments of Intensity Modulated Radiation Therapy (IMRT) treatments. A first-order approximation to the dose error at a point is modeled as the dot product of the dose gradient and the shift vector of the point due to the rotational error. The analysis method is applied to a previously published set of optimized fluences for a 50 MV IMRT pelvis irradiation. Three of the published cases exhibiting a wide range of modulation are presented; a rectangular open field, a field optimized for a static multileaf collimator defining the portal outline coupled with a single broad bremsstrahlung profile modulation, and a fully modulated field using a physical modulator. To examine the energy dependence of angle setting errors, the study is repeated using the same fluence distributions, but with a dose-spread kernel appropriate for a 6 MV photon beam. The collimator angle error is set to 2 degree, and the dose error determined with both a centrally located isocenter and an isocenter chosen to model a split-field geometry. The dose error due to a 2 degree gantry setting error is assessed at a plane 10 cm distal to the isocenter. The mathematical form of the dose error due to couch motion is similar to the other two errors, so the dose error resulting from a couch angle missetting is not presented. The magnitude of the errors is largest for the 6 MV beam, while the volume encompassed by the errors is greater for the 50 MV beam. The gantry error yields the largest dose error values, with the 6 MV modulated case presenting dose errors of greater than 40%.

Humans↗

Frequency modulation detection interference produced by asynchronous and nonsimultaneous interferers.

The effect of asynchronous and nonsimultaneous interferers on detection of sinusoidal frequency modulation (FM) was compared with the effect of a synchronous interferer. In a two-interval, two-alternative forced-choice (2I-2AFC) adaptive procedure, listeners had to detect FM with a modulation frequency of 15 Hz, imposed on a 1-kHz sinusoidal carrier (the target). The 200-ms target was presented either alone (baseline condition), or with an interferer whose timing relative to the target was varied. The interferer was a 2.3-kHz sinusoidal carrier which was also frequency modulated at a rate of 15 Hz. Experiment one showed that thresholds for detection of FM increased significantly, both with a synchronous FM interferer, and also with asynchronous interferers (starting 200 ms before and stopping 200 ms after the target). Moreover, "gapped" interferers that were turned off during presentation of the target (presented for 200 ms before and for 200 ms after the target but not simultaneously) produced the same significant increase in thresholds as an asynchronous interferer that was not interrupted. In contrast, thresholds were not affected by the presence of a gapped unmodulated sinusoidal interferer. Experiment two showed that increasing the duration of the silent gap (centered on presentation of the target) between FM interferers from 200 to 600 ms did not abolish the interference. Thus nonsimultaneous FM interferers produced frequency modulation detection interference (FMDI) even when the silent gap between the interferers and target clearly led to the interferers and target being perceived as separate auditory objects. A possible explanation for the findings is the existence of an asymmetry in perception of steady and modulated sounds, as recently proposed by Cusack and Carlyon [Br. J. Audiol. 34.2, 112 (2000)]. Alternative explanations in terms of ringing in a hypothetical modulation filter bank and adaptation seem unlikely.

Adolescent↗

Auditory nerve fiber responses to electric stimulation: modulated and unmodulated pulse trains.

Many modern cochlear implants use sound processing strategies that stimulate the cochlea with modulated pulse trains. Rubinstein et al. [Hear. Res. 127, 108 (1999)] suggested that representation of the modulator in auditory nerve responses might be improved by the addition of a sustained, high-rate, desynchronizing pulse train (DPT). In addition, activity in response to the DPT may mimic the spontaneous activity (SA) in a healthy ear. The goals of this study were to compare responses of auditory nerve fibers in acutely deafened, anesthetized cats elicited by high-rate electric pulse trains delivered through an intracochlear electrode with SA, and to measure responses of these fibers to amplitude-modulated pulse trains superimposed upon a DPT. Responses to pulse trains showed variability from presentation to presentation, but differed from SA in the shape of the envelope of the interval histogram (IH) for pulse rates above 4.8 kpps (kilo pulses per second). These IHs had a prominent mode near 5 ms that was followed by a long tail. Responses to modulated biphasic pulse trains resembled responses to tones in intact ears for small (<10%) modulation depths, suggesting that acousticlike responses to sinusoidal stimuli might be obtained with a DPT. However, realistic responses were only observed over a narrow range of levels and modulation depths. Improved coding of complex stimulus waveforms may be achieved by signal processing strategies for cochlear implants that properly incorporate a DPT.

Acoustic Stimulation↗

Interaction between adenosine triphosphate and mechanically induced modulation of electrically evoked otoacoustic emissions.

It was shown previously that electrically evoked otoacoustic emissions (EEOAEs) can be amplitude modulated by low-frequency bias tones and enhanced by application of adenosine triphosphate (ATP) to scala media. These effects were attributed, respectively, to the mechano-electrical transduction (MET) channels and ATP-gated ion channels on outer hair cell (OHC) stereocilia, two conductance pathways that appear to be functionally independent and additive in their effects on ionic current through the OHC. In the experiments described here, the separate influences of ATP and MET channel bias on EEOAEs did not combine linearly. Modulated EEOAEs increased in amplitude, but lost modulation at the phase and frequency of the bias tone (except at very high sound levels) after application of ATP to scala media, even though spectral components at the modulation sideband frequencies were still present. Some sidebands underwent phase shifts after ATP. In EEOAEs modulated by tones at lower sound levels, substitution of the original phase values restored modulation to the waveform, which then resembled a linear summation of the separate effects of ATP and low-frequency bias. While the physiological meaning of this procedure is not clear, the result raises the possibility that a secondary effect of ATP on one or more nonlinear stages in the transduction process, which may have caused the phase shifts, obscured linear summation at lower sound levels. In addition, "acoustic enhancement" of the EEOAE may have introduced nonlinear interaction at higher levels of the bias tones.

Adenosine Triphosphate↗

Spectral models of additive and modulation noise in speech and phonatory excitation signals.

The article presents spectral models of additive and modulation noise in speech. The purpose is to learn about the causes of noise in the spectra of normal and disordered voices and to gauge whether the spectral properties of the perturbations of the phonatory excitation signal can be inferred from the spectral properties of the speech signal. The approach to modeling consists of deducing the Fourier series of the perturbed speech, assuming that the Fourier series of the noise and of the clean monocycle-periodic excitation are known. The models explain published data, take into account the effects of supraglottal tremor, demonstrate the modulation distortion owing to vocal tract filtering, establish conditions under which noise cues of different speech signals may be compared, and predict the impossibility of inferring the spectral properties of the frequency modulating noise from the spectral properties of the frequency modulation noise (e.g., phonatory jitter and frequency tremor). The general conclusion is that only phonatory frequency modulation noise is spectrally relevant. Other types of noise in speech are either epiphenomenal, or their spectral effects are masked by the spectral effects of frequency modulation noise.

Fourier Analysis↗

Dynamics of frequency and amplitude modulations in vocalizations produced by eastern towhees, Pipilo erythrophthalmus.

Eastern towhees, Pipilo erythrophthalmus (Emberizidae, Passeriformes), appear to estimate source-SPL using spectral or temporal variables. Nevertheless, vocalizations are dynamic by nature and it remains unclear whether subjects pay attention to correlations between discrete variables or pay attention to the dynamics that these variables summarize. Sine functions are used to describe coarse (slow, < 10 Hz) frequency and amplitude modulations in towhee calls and correlations between variables are identified. Towhee calls are also finely (rapidly, > 400 Hz) modulated in both amplitude and frequency. Fine amplitude and frequency modulations correlate well (occur in phase) over relatively low fundamental frequencies (< approximately 3.5 kHz) and tend to have greater amplitudes and frequencies over these same frequencies. Modulations and correlations between modulations might exist due to stable dynamic interactions that occur within and between the physical forces that function to produce modulations in vocalizations. Results support the hypothesis that towhees communicate within separate sound frequency channels defined to each side of approximately 3.5 kHz.

Animals↗

Frequency modulation detection in cochlear implant subjects.

Frequency modulation (FM) detection was investigated in acoustic and electric hearing to characterize cochlear-implant subjects' ability to detect dynamic frequency changes and to assess the relative contributions of temporal and spectral cues to frequency processing. Difference limens were measured for frequency upward sweeps, downward sweeps, and sinusoidal FM as a function of standard frequency and modulation rate. In electric hearing, factors including electrode position and stimulation level were also studied. Electric hearing data showed that the difference limen increased monotonically as a function of standard frequency regardless of the modulation type, the modulation rate, the electrode position, and the stimulation level. In contrast, acoustic hearing data showed that the difference limen was nearly a constant as a function of standard frequency. This difference was interpreted to mean that temporal cues are used only at low standard frequencies and at low modulation rates. At higher standard frequencies and modulation rates, the reliance on the place cue is increased, accounting for the better performance in acoustic hearing than for electric hearing with single-electrode stimulation. The present data suggest a speech processing strategy that encodes slow frequency changes using lower stimulation rates than those typically employed by contemporary cochlear-implant speech processors.

Adult↗

Auditory processing of real and illusory changes in frequency modulation (FM) phase.

Auditory processing of frequency modulation (FM) was explored. In experiment 1, detection of a tau-radians modulator phase shift deteriorated as modulation rate increased from 2.5 to 20 Hz, for 1- and 6-kHz carriers. In experiment 2, listeners discriminated between two 1-kHz carriers, where, mid-way through, the 10-Hz frequency modulator had either a phase shift or increased in depth by deltaD% for half a modulator period. Discrimination was poorer for deltaD = 4% than for smaller or larger increases. These results are consistent with instantaneous frequency being smoothed by a time window with a total duration of about 110 ms. In experiment 3, the central 200-ms of a 1-s 1-kHz carrier modulated at 5 Hz was replaced by noise, or by a faster FM applied to a more intense 1-kHz carrier. Listeners heard the 5-Hz FM continue at the same depth throughout the stimulus. Experiments 4 and 5 showed that, after an FM tone had been interrupted by a 200-ms noise, listeners were insensitive to the phase at which the FM resumed. It is argued that the auditory system explicitly encodes the presence, and possibly the rate and depth, of FM in a way that does not preserve information on FM phase.

Auditory Threshold↗

Spectral fine-structures of low-frequency modulated distortion product otoacoustic emissions.

Biasing of the cochlear partition with a low-frequency tone can produce an amplitude modulation of distortion product otoacoustic emissions (DPOAEs) in gerbils. In the time domain, odd- versus even-order DPOAEs demonstrated different modulation patterns depending on the bias tone phase. In the frequency domain, multiple sidebands are presented on either side of each DPOAE component. These sidebands were located at harmonic multiples of the biasing frequency from the DPOAE component. For odd-order DPOAEs, sidebands at the even-multiples of the biasing frequency were enhanced, while for even-order DPOAEs, the sidebands at the odd-multiples were elevated. When a modulation in DPOAE magnitude was presented, the magnitudes of the sidebands were enhanced and even greater than the DPOAEs. The amplitudes of these sidebands varied with the levels of the bias tone and two primary tones. The results indicate that the maximal amplitude modulations of DPOAEs occur at a confined bias and primary level space. This can provide a guide for optimal selections of signal conditions for better recordings of low-frequency modulated DPOAEs in future research and applications. Spectral fine-structure and its unique relation to the DPOAE modulation pattern may be useful for direct acquisition of cochlear transducer nonlinearity from a simple spectral analysis.

Acoustic Stimulation↗

Differential sensitivity to tonal frequency and to the rate of amplitude modulation of broadband noise by normally hearing listeners.

Differential sensitivities for tones which varied in frequency (containing cues for place and periodicity) and for broadband noise which varied in the rate of sinusoidal amplitude modulation (presumably containing only a periodicity cue) were measured at common frequencies and modulation rates of the stimulus for four normally hearing listeners. A forced-choice adaptive psychophysical procedure was used in all measurements. Through 60 Hz, tonal-frequency and rate discrimination were similar (on average, 2.5-3.0 Hz) across listeners. From 80-400 Hz, differential sensitivity for tones was between 1.0 and 2.0 Hz, whereas values for rate discrimination increased almost linearly from about 3.6 to 122.0 Hz. Apparently, differential sensitivities for both tonal frequency and modulation rate are mediated similarly, presumably by the same (periodicity) mechanism, through 60 Hz. Above 60 Hz, the listener is more sensitive to differences in tonal frequency than modulation rate. Detection thresholds for sinusoidal amplitude modulation of noise also were measured for these listeners. An average modulation threshold function was obtained and a half-power frequency was estimated for the function at 60 Hz; from this value a time constant of 2.65 ms may be derived, which is consistent with time constants measured by other psychophysical methods. These data further point to some change in perceptual quality above about 60 Hz, that frequency above which we found tonal-frequency and rate discrimination functions to separate.

Adult↗

Lateralization of sinusoidally amplitude-modulated tones: effects of spectral locus and temporal variation.

It has long been recognized that listeners are sensitive to interaural temporal disparities (ITDs) of low-frequency (i.e., below 1600 Hz) stimuli. Within the last three decades, it has often been demonstrated that listeners are also sensitive to ITDs within the envelope of high-frequency, complex stimuli. Because these studies, for the most part, employed discrimination tasks, few data exist concerning the extent of laterality produced by ITDs as a function of the spectral locus of the stimulus. To this end, we employed an acoustic "pointing" task in which listeners varied the interaural intensity difference of a 500-Hz narrow-band noise (the pointer) so that it matched the intracranial position of a second, experimenter-controlled stimulus (the target). Targets were sinusoidally amplitude-modulated tones centered on 500 Hz, 1, 2, 3, or 4 kHz and modulated at rates ranging from 50 to 800 Hz. Targets were presented with either the entire waveform delayed or with only the envelope delayed. Our results suggest that: (1) for low-frequency targets, lateralization is influenced by ITDs in the envelope but is dominated by ITDs in the fine structure; (2) for high-frequency targets, envelope-based delays produce displacements of the acoustic images which are affected greatly by the rate of modulation; rather large extents of laterality could be produced with high rates of modulation; these data are consistent with those obtained previously in discrimination experiments; (3) for low rates of modulation (e.g., 100 Hz), delays of the entire waveform (both envelope and fine structure) produce much greater displacements of the acoustic image for low-frequency than for high-frequency targets (where fine-structure-based cues are not utilizable); (4) there appear to be no consistent relations among extent of laterality, rate of modulation, and the frequency of the carrier within and across listeners.

Adult↗