The neurotoxicity of acrylamide

The experiments described in this thesis compared conventional methods of screening for neurotoxins with potential electrophysiological and pharmacological tests in an attempt to improve the sensitivity of detection of progressive distal neuropathy. Adult male albino mice were dosed orally with the neurotoxicant acylamide and subjected to a test of limb strength and co-ordination and a functional observational battery. These methods established a no observable effect level of 10 mg/kg. A dose of 200 mg/kg resulted in abnormalities of gait and reduced limb strength and/or co-ordination. Analysis of the in vitro 'jitter' of the latency of trains of action potentials evoked at a frequency of 30 Hz in the mouse phrenic nerve/hemidiaphragm preparation showed this technique to be unsuitable for detection of the early phases of acrylamide induced peripheral neuropathy (l00 mg/kg). The evoked and spontaneous twitch responses of the hemidiaphragm preparation following in vitro exposure to the organophosphorous anticholinesterase compound ecothiopate were altered by in vivo pre treatment with acrylamide. Acrylamide caused an increase in the time course of the potentiation of stimulated twitches and a decrease in the maximum potentiation. Spontaneous twitches were reduced in amplitude and frequency. These effects occurred at an acrylamide dose level insufficient to cause clinical signs of neuropathy. Investigations into the mechanisms underlying these observations yielded the following observations. Analysis of miniature endplate potentials at this dose level indicated prolongation of the life of acetylcholine in the synaptic cleft but the implied decrease in cholinesterase activity could not be demonstrated biochemically or histologically. The electrical excitability of the nerve terminal region of phrenic motor nerves was reduced following acrylamide although a possible compromise of antidromic action potential conduction could not be confirmed. There was no histopathological evidence of neuropathy at this dose level. Further exploration of this phenomenon is desirable in order to ascertain whether the effect is specific to acrylamide and/or ecothiopate and to elucidate the mechanisms behind these novel observations.

Pulse shaping in mode-locked ring-cavity fibre lasers

By means of extensive numerical modelling we have demonstrated the possibility of nonlinear pulse shaping in a mode-locked fibre laser using control of the intra-cavity propagation dynamics by adjustment of the normal net dispersion and integrated gain. Beside self-similar mode-locking, the existence of a novel type of pulse shaping regime that produces pulses with a triangular temporal intensity profile and a linear frequency chirp has been observed.

Parabolic optical pulses under the action of the third-order dispersion

Recent developments in nonlinear optics reveal an interesting class of pulses with a parabolic intensity profile in the energy-containing core and a linear frequency chirp that can propagate in a fiber with normal group-velocity dispersion. Parabolic pulses propagate in a stable selfsimilar manner, holding certain relations (scaling) between pulse power, width, and chirp parameter. In the additional presence of linear amplification, they enjoy the remarkable property of representing a common asymptotic state (or attractor) for arbitrary initial conditions. Analytically, self-similar (SS) parabolic pulses can be found as asymptotic, approximate solutions of the nonlinear Schr¨odinger equation (NLSE) with gain in the semi-classical (largeamplitude/small-dispersion) limit. By analogy with the well-known stable dynamics of solitary waves - solitons, these SS parabolic pulses have come to be known as similaritons. In practical fiber systems, inherent third-order dispersion (TOD) in the fiber always introduces a certain degree of asymmetry in the structure of the propagating pulse, eventually leading to pulse break-up. To date, there is no analytic theory of parabolic pulses under the action of TOD. Here, we develop aWKB perturbation analysis that describes the effect of weak TOD on the parabolic pulse solution of the NLSE in a fiber gain medium. The induced perturbation in phase and amplitude can be found to any order. The theoretical model predicts with sufficient accuracy the pulse structural changes induced by TOD, which are observed through direct numerical NLSE simulations.

Parabolic optical pulses under the action of the third-order dispersion

Recent developments in nonlinear optics reveal an interesting class of pulses with a parabolic intensity profile in the energy-containing core and a linear frequency chirp that can propagate in a fiber with normal group-velocity dispersion. Parabolic pulses propagate in a stable selfsimilar manner, holding certain relations (scaling) between pulse power, width, and chirp parameter. In the additional presence of linear amplification, they enjoy the remarkable property of representing a common asymptotic state (or attractor) for arbitrary initial conditions. Analytically, self-similar (SS) parabolic pulses can be found as asymptotic, approximate solutions of the nonlinear Schr¨odinger equation (NLSE) with gain in the semi-classical (largeamplitude/small-dispersion) limit. By analogy with the well-known stable dynamics of solitary waves - solitons, these SS parabolic pulses have come to be known as similaritons. In practical fiber systems, inherent third-order dispersion (TOD) in the fiber always introduces a certain degree of asymmetry in the structure of the propagating pulse, eventually leading to pulse break-up. To date, there is no analytic theory of parabolic pulses under the action of TOD. Here, we develop aWKB perturbation analysis that describes the effect of weak TOD on the parabolic pulse solution of the NLSE in a fiber gain medium. The induced perturbation in phase and amplitude can be found to any order. The theoretical model predicts with sufficient accuracy the pulse structural changes induced by TOD, which are observed through direct numerical NLSE simulations.

Pulse shaping in mode-locked ring-cavity fibre lasers

By means of extensive numerical modelling we have demonstrated the possibility of nonlinear pulse shaping in a mode-locked fibre laser using control of the intra-cavity propagation dynamics by adjustment of the normal net dispersion and integrated gain. Beside self-similar mode-locking, the existence of a novel type of pulse shaping regime that produces pulses with a triangular temporal intensity profile and a linear frequency chirp has been observed.

Effects of the rate of formant-frequency variation on the grouping of formants in speech perception

How speech is separated perceptually from other speech remains poorly understood. Recent research suggests that the ability of an extraneous formant to impair intelligibility depends on the modulation of its frequency, but not its amplitude, contour. This study further examined the effect of formant-frequency variation on intelligibility by manipulating the rate of formant-frequency change. Target sentences were synthetic three-formant (F1?+?F2?+?F3) analogues of natural utterances. Perceptual organization was probed by presenting stimuli dichotically (F1?+?F2C?+?F3C; F2?+?F3), where F2C?+?F3C constitute a competitor for F2 and F3 that listeners must reject to optimize recognition. Competitors were derived using formant-frequency contours extracted from extended passages spoken by the same talker and processed to alter the rate of formant-frequency variation, such that rate scale factors relative to the target sentences were 0, 0.25, 0.5, 1, 2, and 4 (0?=?constant frequencies). Competitor amplitude contours were either constant, or time-reversed and rate-adjusted in parallel with the frequency contour. Adding a competitor typically reduced intelligibility; this reduction increased with competitor rate until the rate was at least twice that of the target sentences. Similarity in the results for the two amplitude conditions confirmed that formant amplitude contours do not influence across-formant grouping. The findings indicate that competitor efficacy is not tuned to the rate of the target sentences; most probably, it depends primarily on the overall rate of frequency variation in the competitor formants. This suggests that, when segregating the speech of concurrent talkers, differences in speech rate may not be a significant cue for across-frequency grouping of formants.

Effects of differences in fundamental frequency on across-formant grouping in speech perception

In an isolated syllable, a formant will tend to be segregated perceptually if its fundamental frequency (F0) differs from that of the other formants. This study explored whether similar results are found for sentences, and specifically whether differences in F0 (?F0) also influence across-formant grouping in circumstances where the exclusion or inclusion of the manipulated formant critically determines speech intelligibility. Three-formant (F1 + F2 + F3) analogues of almost continuously voiced natural sentences were synthesized using a monotonous glottal source (F0 = 150 Hz). Perceptual organization was probed by presenting stimuli dichotically (F1 + F2C + F3; F2), where F2C is a competitor for F2 that listeners must resist to optimize recognition. Competitors were created using time-reversed frequency and amplitude contours of F2, and F0 was manipulated (?F0 = ±8, ±2, or 0 semitones relative to the other formants). Adding F2C typically reduced intelligibility, and this reduction was greatest when ?F0 = 0. There was an additional effect of absolute F0 for F2C, such that competitor efficacy was greater for higher F0s. However, competitor efficacy was not due to energetic masking of F3 by F2C. The results are consistent with the proposal that a grouping “primitive” based on common F0 influences the fusion and segregation of concurrent formants in sentence perception.

Build-up of auditory stream segregation induced by tone sequences of constant or alternating frequency and the resetting effects of single deviants

A sequence of constant-frequency tones can promote streaming in a subsequent sequence of alternating-frequency tones, but why this effect occurs is not fully understood and its time course has not been investigated. Experiment 1 used a 2.0-s-long constant-frequency inducer (10 repetitions of a low-frequency pure tone) to promote segregation in a subsequent, 1.2-s test sequence of alternating low- and high-frequency tones. Replacing the final inducer tone with silence substantially reduced reported test-sequence segregation. This reduction did not occur when either the 4th or 7th inducer was replaced with silence. This suggests that a change at the induction/test-sequence boundary actively resets build-up, rather than less segregation occurring simply because fewer inducer tones were presented. Furthermore, Experiment 2 found that a constant-frequency inducer produced its maximum segregation-promoting effect after only three tones—this contrasts with the more gradual build-up typically observed for alternating-frequency sequences. Experiment 3 required listeners to judge continuously the grouping of 20-s test sequences. Constant-frequency inducers were considerably more effective at promoting segregation than alternating ones; this difference persisted for ~10 s. In addition, resetting arising from a single deviant (longer tone) was associated only with constant-frequency inducers. Overall, the results suggest that constant-frequency inducers promote segregation by capturing one subset of test-sequence tones into an ongoing, preestablished stream, and that a deviant tone may reduce segregation by disrupting this capture. These findings offer new insight into the dynamics of stream segregation, and have implications for the neural basis of streaming and the role of attention in stream formation. (PsycINFO Database Record (c) 2013 APA, all rights reserved)

Formant-frequency variation and its effects on across-formant grouping in speech perception

How speech is separated perceptually from other speech remains poorly understood. In a series of experiments, perceptual organisation was probed by presenting three-formant (F1+F2+F3) analogues of target sentences dichotically, together with a competitor for F2 (F2C), or for F2+F3, which listeners must reject to optimise recognition. To control for energetic masking, the competitor was always presented in the opposite ear to the corresponding target formant(s). Sine-wave speech was used initially, and different versions of F2C were derived from F2 using separate manipulations of its amplitude and frequency contours. F2Cs with time-varying frequency contours were highly effective competitors, whatever their amplitude characteristics, whereas constant-frequency F2Cs were ineffective. Subsequent studies used synthetic-formant speech to explore the effects of manipulating the rate and depth of formant-frequency change in the competitor. Competitor efficacy was not tuned to the rate of formant-frequency variation in the target sentences; rather, the reduction in intelligibility increased with competitor rate relative to the rate for the target sentences. Therefore, differences in speech rate may not be a useful cue for separating the speech of concurrent talkers. Effects of competitors whose depth of formant-frequency variation was scaled by a range of factors were explored using competitors derived either by inverting the frequency contour of F2 about its geometric mean (plausibly speech-like pattern) or by using a regular and arbitrary frequency contour (triangle wave, not plausibly speech-like) matched to the average rate and depth of variation for the inverted F2C. Competitor efficacy depended on the overall depth of frequency variation, not depth relative to that for the other formants. Furthermore, the triangle-wave competitors were as effective as their more speech-like counterparts. Overall, the results suggest that formant-frequency variation is critical for the across-frequency grouping of formants but that this grouping does not depend on speech-specific constraints.

Build-up of auditory stream segregation induced by tone sequences of constant or alternating frequency and the resetting effects of single deviants

A sequence of constant-frequency tones can promote streaming in a subsequent sequence of alternating-frequency tones, but why this effect occurs is not fully understood and its time course has not been investigated. Experiment 1 used a 2.0-s-long constant-frequency inducer (10 repetitions of a low-frequency pure tone) to promote segregation in a subsequent, 1.2-s test sequence of alternating low- and high-frequency tones. Replacing the final inducer tone with silence substantially reduced reported test-sequence segregation. This reduction did not occur when either the 4th or 7th inducer was replaced with silence. This suggests that a change at the induction/test-sequence boundary actively resets build-up, rather than less segregation occurring simply because fewer inducer tones were presented. Furthermore, Experiment 2 found that a constant-frequency inducer produced its maximum segregation-promoting effect after only three tones—this contrasts with the more gradual build-up typically observed for alternating-frequency sequences. Experiment 3 required listeners to judge continuously the grouping of 20-s test sequences. Constant-frequency inducers were considerably more effective at promoting segregation than alternating ones; this difference persisted for ~10 s. In addition, resetting arising from a single deviant (longer tone) was associated only with constant-frequency inducers. Overall, the results suggest that constant-frequency inducers promote segregation by capturing one subset of test-sequence tones into an ongoing, preestablished stream, and that a deviant tone may reduce segregation by disrupting this capture. These findings offer new insight into the dynamics of stream segregation, and have implications for the neural basis of streaming and the role of attention in stream formation. (PsycINFO Database Record (c) 2013 APA, all rights reserved)

Formant-frequency variation and its effects on across-formant grouping in speech perception

How speech is separated perceptually from other speech remains poorly understood. In a series of experiments, perceptual organisation was probed by presenting three-formant (F1+F2+F3) analogues of target sentences dichotically, together with a competitor for F2 (F2C), or for F2+F3, which listeners must reject to optimise recognition. To control for energetic masking, the competitor was always presented in the opposite ear to the corresponding target formant(s). Sine-wave speech was used initially, and different versions of F2C were derived from F2 using separate manipulations of its amplitude and frequency contours. F2Cs with time-varying frequency contours were highly effective competitors, whatever their amplitude characteristics, whereas constant-frequency F2Cs were ineffective. Subsequent studies used synthetic-formant speech to explore the effects of manipulating the rate and depth of formant-frequency change in the competitor. Competitor efficacy was not tuned to the rate of formant-frequency variation in the target sentences; rather, the reduction in intelligibility increased with competitor rate relative to the rate for the target sentences. Therefore, differences in speech rate may not be a useful cue for separating the speech of concurrent talkers. Effects of competitors whose depth of formant-frequency variation was scaled by a range of factors were explored using competitors derived either by inverting the frequency contour of F2 about its geometric mean (plausibly speech-like pattern) or by using a regular and arbitrary frequency contour (triangle wave, not plausibly speech-like) matched to the average rate and depth of variation for the inverted F2C. Competitor efficacy depended on the overall depth of frequency variation, not depth relative to that for the other formants. Furthermore, the triangle-wave competitors were as effective as their more speech-like counterparts. Overall, the results suggest that formant-frequency variation is critical for the across-frequency grouping of formants but that this grouping does not depend on speech-specific constraints. © Springer Science+Business Media New York 2013.

Build-up of auditory stream segregation induced by tone sequences of constant or alternating frequency and the resetting effects of single deviants

Three experiments investigated the dynamics of auditory stream segregation. Experiment 1 used a 2.0-s constant-frequency inducer (10 repetitions of a low-frequency pure tone) to promote segregation in a subsequent, 1.2-s test sequence of alternating low- and high-frequency tones. Replacing the final inducer tone with silence reduced reported test-sequence segregation substantially. This reduction did not occur when either the 4th or 7th inducer was replaced with silence. This suggests that a change at the induction/test-sequence boundary actively resets buildup, rather than less segregation occurring simply because fewer inducer tones were presented. Furthermore, Experiment 2 found that a constant-frequency inducer produced its maximum segregation-promoting effect after only 3 tone cycles - this contrasts with the more gradual build-up typically observed for alternating sequences. Experiment 3 required listeners to judge continuously the grouping of 20-s test sequences. Constant-frequency inducers were considerably more effective at promoting segregation than alternating ones; this difference persisted for ∼10 s. In addition, resetting arising from a single deviant (longer tone) was associated only with constant-frequency inducers. Overall, the results suggest that constant-frequency inducers promote segregation by capturing one subset of test-sequence tones into an on-going, pre-established stream and that a deviant tone may reduce segregation by disrupting this capture. © 2013 Acoustical Society of America.

Informational masking and the effects of differences in fundamental frequency and fundamental-frequency contour on phonetic integration in a formant ensemble

This study explored the effects on speech intelligibility of across-formant differences in fundamental frequency (ΔF0) and F0 contour. Sentence-length speech analogues were presented dichotically (left=F1+F3; right=F2), either alone or—because competition usually reveals grouping cues most clearly—accompanied in the left ear by a competitor for F2 (F2C) that listeners must reject to optimize recognition. F2C was created by inverting the F2 frequency contour. In experiment 1, all left-ear formants shared the same constant F0 and ΔF0F2 was 0 or ±4 semitones. In experiment 2, all left-ear formants shared the natural F0 contour and that for F2 was natural, constant, exaggerated, or inverted. Adding F2C lowered keyword scores, presumably because of informational masking. The results for experiment 1 were complicated by effects associated with the direction of ΔF0F2; this problem was avoided in experiment 2 because all four F0 contours had the same geometric mean frequency. When the target formants were presented alone, scores were relatively high and did not depend on the F0F2 contour. F2C impact was greater when F2 had a different F0 contour from the other formants. This effect was a direct consequence of the associated ΔF0; the F0F2 contour per se did not influence competitor impact.

Effects of the build-up and resetting of auditory stream segregation on temporal discrimination

The tendency to hear a tone sequence as 2 or more streams (segregated) builds up, but a sudden change in properties can reset the percept to 1 stream (integrated). This effect has not hitherto been explored using an objective measure of streaming. Stimuli comprised a 2.0-s fixed-frequency inducer followed by a 0.6-s test sequence of alternating pure tones (3 low [L]-high [H] cycles). Listeners compared intervals for which the test sequence was either isochronous or the H tones were slightly delayed. Resetting of segregation should make identifying the anisochronous interval easier. The HL frequency separation was varied (0-12 semitones), and properties of the inducer and test sequence were set to the same or different values. Inducer properties manipulated were frequency, number of onsets (several short bursts vs. one continuous tone), tone:silence ratio (short vs. extended bursts), level, and lateralization. All differences between the inducer and the L tones reduced temporal discrimination thresholds toward those for the no-inducer case, including properties shown previously not to affect segregation greatly. Overall, it is concluded that abrupt changes in a sequence cause resetting and improve subsequent temporal discrimination. (PsycINFO Database Record © 2009 APA, all rights reserved)

Grouping and the pitch of a mistuned fundamental component:effects of applying simultaneous multiple mistunings to the other harmonics

Mistuning a harmonic produces an exaggerated change in its pitch. This occurs because the component becomes inconsistent with the regular pattern that causes the other harmonics (constituting the spectral frame) to integrate perceptually. These pitch shifts were measured when the fundamental (F0) component of a complex tone (nominal F0 frequency = 200 Hz) was mistuned by +8% and -8%. The pitch-shift gradient was defined as the difference between these values and its magnitude was used as a measure of frame integration. An independent and random perturbation (spectral jitter) was applied simultaneously to most or all of the frame components. The gradient magnitude declined gradually as the degree of jitter increased from 0% to ±40% of F0. The component adjacent to the mistuned target made the largest contribution to the gradient, but more distant components also contributed. The stimuli were passed through an auditory model, and the exponential height of the F0-period peak in the averaged summary autocorrelation function correlated well with the gradient magnitude. The fit improved when the weighting on more distant channels was attenuated by a factor of three per octave. The results are consistent with a grouping mechanism that computes a weighted average of periodicity strength across several components. © 2006 Elsevier B.V. All rights reserved.